Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3....

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Target organ toxicity

Transcript of Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3....

Page 1: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Target organ toxicity

기억나세요 약물상호작용에 의해 독성이 커질 수 있음을 알고 있다 AmphotericinB와 flucytosine의 상호작용을 알고 있다 AmphotericinB와 ketoconazole의 상호작용을 알고 있다 오키나와 투구꽃 사건의 기전을 설명할 수 있다 복어는 독을 만들지 않는다 초회통과대사를 설명할 수 있다 와파린의 약물 상호작용을 설명할 수 있다 약물-식품 상호작용의 중요성을 설명할 수 있다

1 Target organ toxicity Liver dual blood supply (hepatic artery portal vein) biotransformation vs bioactivation acetaminophen carbon tetrachloride halogenated benzenes isoniazid aflatoxin B aromatic amines chloroform

CHCl3

CYP2E1 GSH Detoxified product

Hepatotoxicity

(chemical weapon during World War I)

Chloroform

The use of chemical weapons in World War I ranged from disabling chemicals such as tear gas and the severe mustard gas to lethal agents like phosgene and chlorine The killing capacity of gas however was limited ndash only four percent of combat deaths were caused by gas

chemical weapons in World War I

anesthesia FOR

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Biotrasformation vs bioactivation Drug-metabolizing enz can not see the toxicity of xenobiotics Xenobiotics Phase I CYP microsome oxidation hydrolysis Phase II conjugating enzyme cytosol

Xeno- biotics

Secondary product

Primary product

Phase I Phase II

conjugtion

lipophilic excretion

hydrophilic

oxidation

hydrolysis

Cytochrome P450

The Human Genome Project has identified 57 genes coding for the various cytochrome P450 enzymes 1 Enough Reduced substrate specificity One

enzyme metabolize several drugs or chemical

2 Feed-back mechanism Enzyme induction mainly by substrate Species variation individual difference

CNS Neurons are particularly susceptible because they have a high metabolic rate that requires a sustained delivery of oxygen and nutrients (glucose) Sustained reductions in oxygen and glucose supply CNS damage Acrylamide n-hexane n-hexane 25-hexanedione (biotransformation by P450) binds to amino groups of neurofilaments and cross-link neurofilaments axonal transport retarded axonal atropy Mature neurons are lack of regenerative repair Neurotoxicity is often delayed

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 2: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

기억나세요 약물상호작용에 의해 독성이 커질 수 있음을 알고 있다 AmphotericinB와 flucytosine의 상호작용을 알고 있다 AmphotericinB와 ketoconazole의 상호작용을 알고 있다 오키나와 투구꽃 사건의 기전을 설명할 수 있다 복어는 독을 만들지 않는다 초회통과대사를 설명할 수 있다 와파린의 약물 상호작용을 설명할 수 있다 약물-식품 상호작용의 중요성을 설명할 수 있다

1 Target organ toxicity Liver dual blood supply (hepatic artery portal vein) biotransformation vs bioactivation acetaminophen carbon tetrachloride halogenated benzenes isoniazid aflatoxin B aromatic amines chloroform

CHCl3

CYP2E1 GSH Detoxified product

Hepatotoxicity

(chemical weapon during World War I)

Chloroform

The use of chemical weapons in World War I ranged from disabling chemicals such as tear gas and the severe mustard gas to lethal agents like phosgene and chlorine The killing capacity of gas however was limited ndash only four percent of combat deaths were caused by gas

chemical weapons in World War I

anesthesia FOR

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Biotrasformation vs bioactivation Drug-metabolizing enz can not see the toxicity of xenobiotics Xenobiotics Phase I CYP microsome oxidation hydrolysis Phase II conjugating enzyme cytosol

Xeno- biotics

Secondary product

Primary product

Phase I Phase II

conjugtion

lipophilic excretion

hydrophilic

oxidation

hydrolysis

Cytochrome P450

The Human Genome Project has identified 57 genes coding for the various cytochrome P450 enzymes 1 Enough Reduced substrate specificity One

enzyme metabolize several drugs or chemical

2 Feed-back mechanism Enzyme induction mainly by substrate Species variation individual difference

CNS Neurons are particularly susceptible because they have a high metabolic rate that requires a sustained delivery of oxygen and nutrients (glucose) Sustained reductions in oxygen and glucose supply CNS damage Acrylamide n-hexane n-hexane 25-hexanedione (biotransformation by P450) binds to amino groups of neurofilaments and cross-link neurofilaments axonal transport retarded axonal atropy Mature neurons are lack of regenerative repair Neurotoxicity is often delayed

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 3: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

1 Target organ toxicity Liver dual blood supply (hepatic artery portal vein) biotransformation vs bioactivation acetaminophen carbon tetrachloride halogenated benzenes isoniazid aflatoxin B aromatic amines chloroform

CHCl3

CYP2E1 GSH Detoxified product

Hepatotoxicity

(chemical weapon during World War I)

Chloroform

The use of chemical weapons in World War I ranged from disabling chemicals such as tear gas and the severe mustard gas to lethal agents like phosgene and chlorine The killing capacity of gas however was limited ndash only four percent of combat deaths were caused by gas

chemical weapons in World War I

anesthesia FOR

REFERENCE ONLY

Biotrasformation vs bioactivation Drug-metabolizing enz can not see the toxicity of xenobiotics Xenobiotics Phase I CYP microsome oxidation hydrolysis Phase II conjugating enzyme cytosol

Xeno- biotics

Secondary product

Primary product

Phase I Phase II

conjugtion

lipophilic excretion

hydrophilic

oxidation

hydrolysis

Cytochrome P450

The Human Genome Project has identified 57 genes coding for the various cytochrome P450 enzymes 1 Enough Reduced substrate specificity One

enzyme metabolize several drugs or chemical

2 Feed-back mechanism Enzyme induction mainly by substrate Species variation individual difference

CNS Neurons are particularly susceptible because they have a high metabolic rate that requires a sustained delivery of oxygen and nutrients (glucose) Sustained reductions in oxygen and glucose supply CNS damage Acrylamide n-hexane n-hexane 25-hexanedione (biotransformation by P450) binds to amino groups of neurofilaments and cross-link neurofilaments axonal transport retarded axonal atropy Mature neurons are lack of regenerative repair Neurotoxicity is often delayed

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 4: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Chloroform

The use of chemical weapons in World War I ranged from disabling chemicals such as tear gas and the severe mustard gas to lethal agents like phosgene and chlorine The killing capacity of gas however was limited ndash only four percent of combat deaths were caused by gas

chemical weapons in World War I

anesthesia FOR

REFERENCE ONLY

Biotrasformation vs bioactivation Drug-metabolizing enz can not see the toxicity of xenobiotics Xenobiotics Phase I CYP microsome oxidation hydrolysis Phase II conjugating enzyme cytosol

Xeno- biotics

Secondary product

Primary product

Phase I Phase II

conjugtion

lipophilic excretion

hydrophilic

oxidation

hydrolysis

Cytochrome P450

The Human Genome Project has identified 57 genes coding for the various cytochrome P450 enzymes 1 Enough Reduced substrate specificity One

enzyme metabolize several drugs or chemical

2 Feed-back mechanism Enzyme induction mainly by substrate Species variation individual difference

CNS Neurons are particularly susceptible because they have a high metabolic rate that requires a sustained delivery of oxygen and nutrients (glucose) Sustained reductions in oxygen and glucose supply CNS damage Acrylamide n-hexane n-hexane 25-hexanedione (biotransformation by P450) binds to amino groups of neurofilaments and cross-link neurofilaments axonal transport retarded axonal atropy Mature neurons are lack of regenerative repair Neurotoxicity is often delayed

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

FOR REFERENCE

ONLY

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 5: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Biotrasformation vs bioactivation Drug-metabolizing enz can not see the toxicity of xenobiotics Xenobiotics Phase I CYP microsome oxidation hydrolysis Phase II conjugating enzyme cytosol

Xeno- biotics

Secondary product

Primary product

Phase I Phase II

conjugtion

lipophilic excretion

hydrophilic

oxidation

hydrolysis

Cytochrome P450

The Human Genome Project has identified 57 genes coding for the various cytochrome P450 enzymes 1 Enough Reduced substrate specificity One

enzyme metabolize several drugs or chemical

2 Feed-back mechanism Enzyme induction mainly by substrate Species variation individual difference

CNS Neurons are particularly susceptible because they have a high metabolic rate that requires a sustained delivery of oxygen and nutrients (glucose) Sustained reductions in oxygen and glucose supply CNS damage Acrylamide n-hexane n-hexane 25-hexanedione (biotransformation by P450) binds to amino groups of neurofilaments and cross-link neurofilaments axonal transport retarded axonal atropy Mature neurons are lack of regenerative repair Neurotoxicity is often delayed

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 6: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Cytochrome P450

The Human Genome Project has identified 57 genes coding for the various cytochrome P450 enzymes 1 Enough Reduced substrate specificity One

enzyme metabolize several drugs or chemical

2 Feed-back mechanism Enzyme induction mainly by substrate Species variation individual difference

CNS Neurons are particularly susceptible because they have a high metabolic rate that requires a sustained delivery of oxygen and nutrients (glucose) Sustained reductions in oxygen and glucose supply CNS damage Acrylamide n-hexane n-hexane 25-hexanedione (biotransformation by P450) binds to amino groups of neurofilaments and cross-link neurofilaments axonal transport retarded axonal atropy Mature neurons are lack of regenerative repair Neurotoxicity is often delayed

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 7: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

CNS Neurons are particularly susceptible because they have a high metabolic rate that requires a sustained delivery of oxygen and nutrients (glucose) Sustained reductions in oxygen and glucose supply CNS damage Acrylamide n-hexane n-hexane 25-hexanedione (biotransformation by P450) binds to amino groups of neurofilaments and cross-link neurofilaments axonal transport retarded axonal atropy Mature neurons are lack of regenerative repair Neurotoxicity is often delayed

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 8: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Poisoning from touchscreen cleaner In February 2010 reports surfaced saying that an employee of Wintek Corporation in China (a company that manufactures touchscreen components including Apple for use in its iPod touch and iPhone) died in August 2009 due to hexane poisoning Hexane was used as a replacement for alcohol for cleaning the screens Reports suggest up to 137 Chinese employees required treatment for hexane poisoning around the same time An ABC Foreign Correspondent episode covertly interviewed several women who had been in the hospital for over six months The women claimed that they were exposed to hexane while manufacturing iPhone hardware

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 9: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

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Int J Occup Environ Health 2012 Apr-Jun18(2)147-53 Leukemia and non-Hodgkin lymphoma in semiconductor industry workers in Korea Kim I Kim HJ Lim SY Kongyoo J Source Graduate School of Public Health Yonsei University Korea Abstract Reports of leukemia and non-Hodgkin lymphoma (NHL) cancers known to have a similar pathophysiology among workers in the semiconductor industry have generated much public concern in Korea This paper describes cases reported to the NGO Supporters for the Health and Rights of People in the Semiconductor Industry (SHARPs) We identified demographic characteristics occupational and disease history for 17 leukemia and NHL cases from the Giheung Samsung semiconductor plant diagnosed from November 2007 to January 2011 Patients were relatively young (mean = 28middot5 years SD = 6middot5) at the time of diagnosis and the mean latency period was 104middot3 months (SD = 65middot8) Majority of the cases were fabrication operators (11 workers among 17) and 12 were hired before 2000 Six cases worked in the etching or diffusion process The evidence to confirm the causal relationship between exposures in the semiconductor industry and leukemia or NHL remains insufficient and a more formal independent study of the exposure-disease relationship in this occupation is needed However workers should be protected from the potential exposures immediately

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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FOR REFERENCE

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 10: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Pulmonary Pulmonary system nasopharyngeal and tracheobronchial airways and pulmonary parenchyma (alveoli) Chlorine gas reacts with upper airway fluids and produces hydrochloric acid causing mucosal injury Asbestos macrophages engulf but cannot degrade asbestos particles macrophages ultimately die release degradative enzymes into the interstitium damage adjacent cells repetition of this process eventually leads to progressive fibrosis and restrictive respiratory dysfunction (mesothelioma lung cancer)

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 11: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

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A gift from God silent killer

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 12: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Pulmonary Benzo[a]pyrene and other polycyclic aromatic hydrocarbons biotransformed by cytochrome P450 (Clara cells located in terminal bronchioles type II cells) causes lung cancer Paraquat ingestion or skin contamination bloodstream taken up by type II pneumocytes in lung biotransformation single-electron cyclic reduction-oxidation subsequent formation of superoxide anion radical lipid peroxidation pulmonary toxicity

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

FOR REFERENCE

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Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 13: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Benzo[a]pyrene found in tobacco smoke (including cigarette smoke) was shown to cause genetic damage in lung cells A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue particularly steaks chicken with skin and hamburgers

FOR REFERENCE

ONLY

Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 14: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Kidney delivery of blood-borne toxic substances to the kidney is high because (1) the kidney receives 25 of cardiac output and (2) its functions include filtering concentrating and eliminating toxicants Carbon tetrachloride and chloroform biotransformation in the proximal tubule Heavy metal damage the proximal tubules Immune complexes (to penicillin immune globulins sulfonamides) may cause glomerulonephritis Metallothioneins avidly bind cadmium protecting the kidney and other organs from toxicity if exposure exceeds the binding capacity or if a large amount of the cadmium-MT complex accumulates

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 15: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Cadmium

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 16: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

2 THE IMMUNE SYSTEM Immunosuppression may lead to an increased incidence of bacterial viral and parasitic infections Hypersensitivity reactions Type I anaphylaxis IgE bound to mast cells and basophils histamine release (penicillin) Type II IgG or IgM complement-mediated or other cytotoxic mechanisms (penicillins sulfonamides and quinine) RBC hemolysis Type III serum sickness deposition of antibody-antigen complexes in skin and membranes (antivenin) Type IV cell-mediated hypersensitivity caused by T cells contact dermatitis to (nickel several industrial chemicals and poison ivy)

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 17: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Anaphylaxis - Cause dust penicillin cephalosporin aspirin ibuprofen - throat couphing wheezing swelling blue lips an itchy rash and low blood pressure - up to 1 may die as a result approximately 1500 deaths per year in the United States -is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE) - epinephrine oxygen anti-histamine steroids

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

FOR REFERENCE

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 18: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Quiz 1 Where is IgE mast cell membrane 2 Which cell produce IgE Plasma cell 3 Most chemical drugs are too small to be immunogen How immune cell sensitize them Hapten should bind to protein carrier 4 Can we trust negative patch-test No still we need to watch out

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

FOR REFERENCE

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 19: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Penicillin binds to IgE but does not cross-link IgEs It requires serum protein to cross-link IgEs

Penicillin

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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FOR REFERENCE

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 20: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

3 TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in humans (phocomelia) banned from clinical use in the 1960s Biotransformed by embryonic prostaglandin H synthase New therapeutic activity in leprosy Anti-inflammatory suppression of cytokine (TNF-α) expression Anti-oncogenic inhibition of angiogenesis

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

FOR REFERENCE

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

FOR REFERENCE

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

FOR REFERENCE

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 21: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

4 CARCINOGENESIS caused by radiation viral infection or chemical exposure vinylchloride benzene naphtylamine cigarette smoke ethanol charcoal polyaromatic hydrocarbons Carcinogenic process Biotransformation Initiation Promotion Progression Metastasis Initiator covalently interact with DNA fixation of DNA mutation Promoter increase the incidence of cancers or decrease the latency period for tumor development without interacting with DNA or producing mutations TCDD growth factors and hormones (FSH and LH)

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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ONLY

2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 22: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

4 CARCINOGENESIS Dioxin 2378-Tetrachlorodibenzo-p-dioxin (TCDD) promoter teratogen vietnam agent orange herbicide contaminant one of the most toxic synthetic substances known in laboratory animals (LD50 for male rats and guinea pig are 0022 mgkg and 06 microgkg respectively) the mechanism of death is not known inducer of cytochrome P450 1A1 aryl hydrocarbon receptor (AhR)

Cl

Cl

Cl

Cl

O

O

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

FOR REFERENCE

ONLY

경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

FOR REFERENCE

ONLY

경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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  • 슬라이드 번호 55
Page 23: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

5 TOXIC GASES Among the most toxic gases are CO and volatile cyanides Carbon monoxide The leading cause of death by poisoning CO displaces oxygen from hemoglobin (200 times higher affinity for hemoglobin than oxygen does) CO impairs oxygen release from hemoglobin Early signs nausea headache malaise light-headedness and dizziness Later signs depressed sensorium loss of consciousness seizures and death Heart is particularly susceptible to CO poisoning myocardial ischemia T12 of carboxyhemoglobin (3-4 hrs) 100 oxygen (T12 = 90 min) hyperbaric oxygen (T12 = 20 min)

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

FOR REFERENCE

ONLY

경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

FOR REFERENCE

ONLY

경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 24: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Bingo Brain Syndrome

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

FOR REFERENCE

ONLY

경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

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2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

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불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
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Page 25: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Bingo Brain Syndrome A woman was admitted to hospital complaining of mental confusion She smoked two packs of cigarettes daily and was an ardent bingo player three nights a week Further research revealed that of the 310 bingo players involved 304 smoked The womans diagnosis was CO poisoning Today we worry about deaths due to drunk drivers but we might never know the number of fatalities that occur because chain smokers fall asleep from increased CO in the car

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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2012년 9월 27일 구미 불산가스 누출사고

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2012년 9월 27일 구미 불산가스 누출사고

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불산 (Hydrofluoric acid)

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Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

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In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

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Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

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6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 26: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

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2012년 9월 27일 구미 불산가스 누출사고 구미 가스 누출 사고(龜尾-漏出事故)는 2012년 9월 27일 경상북도 구미시 산동면 봉산리 구미 제4국가산업단지에 위치한 화학제품 생산업체 휴브글로벌에서 플루오린화 수소 가스가 유출되어 23명의 사상자가 발생 (5명이 사망 포함)하고 공장 일대의 주민과 동middot식물들에 대해 엄청난 피해를 준 사고이다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

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ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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  • 슬라이드 번호 55
Page 27: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

FOR REFERENCE

ONLY

경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 경기도가 최근 잇따르는 불산누출 사고로 골머리를 앓고 있다 도는 6일 오전 7시27분께 시흥시 정왕동 시화공단 내에 위치한 윤활유 및 그리스 제조업체인 (주)제이씨에서 100리터의 불산이 누출되는 사고가 발생했다고 밝혔다 다행히 인명 및 재산피해는 발생하지 않았지만 도는 신고접수 즉시 도 공단환경관리사업소 및 소방 인력 38명과 18대의 소방장비를 동원해 탄산칼륨 25들이 20포를 신속히 살포해 방제했다고 밝혔다

FOR REFERENCE

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경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 28: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

FOR REFERENCE

ONLY

경기도 잇따른 불산누출사고 골머리 6일 시흥서 또 불산누출 (수원=뉴스1) 윤상연 기자 입력 20130506 101503 도는 국립환경과학원 한강유역환경청 등과 합동으로 2차 피해발생에 대비 주변 불산 오염도 검사를 실시하고 있다 앞서 2일에는 삼성전자 반도체 화성사업장에서 불산이 누출돼 작업 중이던 인부 3명이 병원으로 이송되는 사고가 발생했다 삼성전자 반도체 화성사업장 11라인에서는 1월28일 불산을 공급해주는 하부공급라인 교체 작업 중 2~10리터 상당의 불산용액이 흘러나와 작업자 1명이 숨지고 4명이 다치는 사고가 발생하기도 했다

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

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Page 29: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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  • 슬라이드 번호 55
Page 30: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

FOR REFERENCE

ONLY

2012년 9월 27일 구미 불산가스 누출사고

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
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Page 31: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

FOR REFERENCE

ONLY

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 32: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

불산 (Hydrofluoric acid)

FOR REFERENCE

ONLY

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
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  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 33: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

FOR REFERENCE

ONLY

Hydrofluoric acid (HF) is a solution of hydrogen fluoride in water It is a valued source of fluorine and is a precursor to numerous pharmaceuticals such as fluoxetine (Prozac) and diverse materials such as PTFE (Teflon) Hydrofluoric acid is a highly corrosive acid capable of dissolving many materials especially oxides Because of its high reactivity toward glass and moderate reactivity toward many metals hydrofluoric acid is usually stored in plastic containers[3]

Hydrogen fluoride gas is an acute poison that may immediately and permanently damage lungs and the corneas of the eyes Aqueous hydrofluoric acid is a contact-poison with the potential for deep initially painless burns and ensuing tissue death By interfering with body calcium metabolism the concentrated acid may also cause systemic toxicity and eventual cardiac arrest and fatality after contact with as little as 160 cm2 (25 square inches) of skin

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
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  • 슬라이드 번호 30
  • 슬라이드 번호 31
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  • 슬라이드 번호 33
  • 슬라이드 번호 34
  • 슬라이드 번호 35
  • 슬라이드 번호 36
  • 슬라이드 번호 37
  • 슬라이드 번호 38
  • 슬라이드 번호 39
  • 슬라이드 번호 40
  • 슬라이드 번호 41
  • 슬라이드 번호 42
  • 슬라이드 번호 43
  • 슬라이드 번호 44
  • 슬라이드 번호 45
  • 슬라이드 번호 46
  • 슬라이드 번호 47
  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 34: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

FOR REFERENCE

ONLY

In the body hydrofluoric acid reacts with the ubiquitous biologically important ions Ca2+ and Mg2+ Formation of insoluble calcium fluoride is proposed as the etiology for both precipitous fall in serum calcium and the severe pain associated with tissue toxicity[10] Thus hydrofluoric acid exposure is often treated with calcium gluconate a source of Ca2+ that sequesters the fluoride ions HF chemical burns can be treated with a water wash and 25 calcium gluconate gel[11][12][13] However because it is absorbed medical treatment is necessary[9] rinsing off is not enough

calcium gluconate

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
  • 슬라이드 번호 7
  • 슬라이드 번호 8
  • 슬라이드 번호 9
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Page 35: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

쉽시다

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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  • 슬라이드 번호 3
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  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 36: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Sarin

Sarin is an organophosphorus compound with the formula [(CH3)2CHO]CH3P(O)F It is a colorless odorless liquid which is used as a chemical weapon 1995 Tokyo sarin gas attacts On the morning of 20 March 1995 Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system killing 12 commuters seriously injuring 54 and affecting 980 more Some estimates claim as many as 5000 people were injured by the sarin

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
  • 슬라이드 번호 7
  • 슬라이드 번호 8
  • 슬라이드 번호 9
  • 슬라이드 번호 10
  • 슬라이드 번호 11
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Page 37: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Sarin

Specifically sarin is a potent inhibitor of the enzyme cholinesterase[7] Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site Fluoride is the leaving group and the resulting phosphoester is robust but biologically inactive[8][9] With the enzyme inhibited acetylcholine builds up in the synapse and continues to act so that any nerve impulses are in effect continually transmitted Normally the acetylcholinesterase breaks down the acetylcholine in the synaptic cleft in order to allow the effector muscle or organ to relax

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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  • 슬라이드 번호 39
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  • 슬라이드 번호 41
  • 슬라이드 번호 42
  • 슬라이드 번호 43
  • 슬라이드 번호 44
  • 슬라이드 번호 45
  • 슬라이드 번호 46
  • 슬라이드 번호 47
  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 38: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

VX gas

VX O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate is an extremely toxic substance (a class of organophosphate compounds) whose only application is in chemical warfare as a nerve agent

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
  • 슬라이드 번호 7
  • 슬라이드 번호 8
  • 슬라이드 번호 9
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  • 슬라이드 번호 13
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  • 슬라이드 번호 16
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  • 슬라이드 번호 55
Page 39: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

THE ROCK

영화 더록에 나오는 이 장면에 사용된 위험물질에는 어떤 것이 있으며 바퀴벌레를 들고 들어간 이유는 무엇일까요

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
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  • 슬라이드 번호 40
  • 슬라이드 번호 41
  • 슬라이드 번호 42
  • 슬라이드 번호 43
  • 슬라이드 번호 44
  • 슬라이드 번호 45
  • 슬라이드 번호 46
  • 슬라이드 번호 47
  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 40: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Atropine Nerve gas

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
  • 슬라이드 번호 7
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  • 슬라이드 번호 9
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  • 슬라이드 번호 11
  • 슬라이드 번호 12
  • 슬라이드 번호 13
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Page 41: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Beauty

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
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Page 42: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna) Jimson weed (Datura stramonium) mandrake (Mandragora officinarum) and other plants of the family Solanaceae It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects It is a competitive antagonist for the muscarinic acetylcholine receptor types M1 M2 M3 M4 and M5[1] It is classified as an anticholinergic drug (parasympatholytic) LD50 400 mgkg (mouse) 100 mgkg (human 추정)

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
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Page 43: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Atropa bella-donna

The species name belladonna (beautiful woman in Italian) comes from the original use of deadly nightshade as a way of dilating womens pupils to make them beautiful

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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Page 44: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Opthalmic use Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle which is normally stimulated by acetylcholine release thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
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Page 45: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

THE ROCK

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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Page 46: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Mark I NAAK The Mark I NAAK or MARK I Kit is United States military nomenclature for the Nerve Agent Antidote Kit[citation needed] It is a dual-chamber autoinjector Two anti-nerve agent drugs mdash atropine sulfate and pralidoxime chloride mdash each in injectable form constitute the kit[citation needed] The kits are only effective against the nerve agents tabun (GA) sarin (GB) soman (GD) and VX[citation needed] A newer model the ATNAA (Antidote Treatment Nerve Agent Auto-Injector)[1] has both the atropine and the pralidoxime in one syringe allowing for simplified administration

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
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Page 47: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase It is used to combat poisoning by organophosphates[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam The Acetylcholinesterase enzyme has two parts to it An acetylcholine molecule bound at both ends to both sites of the enzyme is ldquo ripped in twordquo to form acetic acid and choline In organophosphate poisoning an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ] blocking its activity Pralidoxime is able to attach to the other half [ the unblocked anionic site ] of the acetylcholinesterase enzyme It then binds to the organophosphate the organophosphate changes conformation and loses its binding to the acetylcholinesterase enzyme The conjoined poison antidote then unbinds from the site and thus regenerates the enzyme which is now able to function again

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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Page 48: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

KMARK-1 현재 군에서 사용하고 있는 신경작용제 치료제인 KMARK-1은 2-PAM(Pralidoxime Chloride)이 들어있는 팜자동주사기와 아드로핀 (Atropine)이 들어 있는 아드로핀주사기로 구성되어 있다 정상적인 신경전달계에서는 아세틸콜린(ACh Acetyl Choline)이라는 신경전달 물질이 신경절에서 분비되어 신경전달 작용을 하며 작용이 끝난 후에 아세틸 콜린에스테라제(AChE Acetyl Cholinesterase)에 의해 가수분해되어 아세트산과 콜린으로 분해된다 신경작용제에 중독되면 AChE는 저해(inhibition)되어 ACh을 가수분해시키는 활성을 잃게 된다 따라서 신경전달 물질인 ACh이 체내에 축적되고 과도한 신경전달이 일어나게 되어 신경작용제 중독 증상이 나타나게 된다 그러므로 신경작용제 중독에 의한 해독치료는 아드로핀을 투여하여 아드로핀과 ACh이 ACh 수용체에 경쟁적으로 작용하도록 하여 중독증상을 완화시키고 동시에 옥심해독제(2-PAM 또는 HI-6)를 투여하여 신경작용제에 의해 저해된 AChE를 재활성화(reactivation) 시켜야 효과적이다 KMARK-1에서 팜자동주사기의 주성분인 2-PAM은 신경작용제에 의해 저해된 AChE를 재활성화시켜 신경작용제 중독에 대한 직접적인 치료를 아드로핀주사기의 주성분인 아드로핀은 중독 증상을 완화시켜 주는 역할을 각각 담당한다 그림2에서 보인 바와 같이 아드로핀과 ACh이 ACh수용체(receptor)에 경쟁적으로 결합(binding)하여 ACh에 의한 과도한 신경전달을 차단(blocking) 시켜 중독증상을 완화 시켜 준다 [출처] [방호 무기체계 22편] 신경작용제는 어떻게 해독되는가|작성자 방위사업청

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
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Page 49: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

THE GAS

FOR REFERENCE

ONLY

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
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Page 50: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

Tear gas works by irritating mucous membranes in the eyes nose mouth and lungs and causes crying sneezing coughing difficulty breathing pain in the eyes temporary blindness etc Lachrymators are thought to act by attacking sulphydryl functional groups in enzymes One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes nose and mouth First used in 1915 xylyl bromide Common lachrymators include OC CS CR CN nonivamide bromoacetone phenacyl bromide xylyl bromide and syn-propanethial-S-oxide (from onions) Chloropicrin chloroacetophenone

Tear gas (lacrymatory agent)

FOR REFERENCE

ONLY

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
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  • 슬라이드 번호 38
  • 슬라이드 번호 39
  • 슬라이드 번호 40
  • 슬라이드 번호 41
  • 슬라이드 번호 42
  • 슬라이드 번호 43
  • 슬라이드 번호 44
  • 슬라이드 번호 45
  • 슬라이드 번호 46
  • 슬라이드 번호 47
  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 51: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

6 HEAVY METALS absorption inorganic physical similarity to nutritionally essential metals (lead absorbed by the normal transport protein for iron located in the GI tract mucosa organic well absorbed (lipid soluble) distribution lipid soluble forms CNS (inorganic mercury kidney methylmercury brain) defense mechanism the strong cadmium binding of metallothionein concentrates cadmium in the kidney and reduces its excretion The binding prevents toxicity until the protein is saturated

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
  • 슬라이드 번호 7
  • 슬라이드 번호 8
  • 슬라이드 번호 9
  • 슬라이드 번호 10
  • 슬라이드 번호 11
  • 슬라이드 번호 12
  • 슬라이드 번호 13
  • 슬라이드 번호 14
  • 슬라이드 번호 15
  • 슬라이드 번호 16
  • 슬라이드 번호 17
  • 슬라이드 번호 18
  • 슬라이드 번호 19
  • 슬라이드 번호 20
  • 슬라이드 번호 21
  • 슬라이드 번호 22
  • 슬라이드 번호 23
  • 슬라이드 번호 24
  • 슬라이드 번호 25
  • 슬라이드 번호 26
  • 슬라이드 번호 27
  • 슬라이드 번호 28
  • 슬라이드 번호 29
  • 슬라이드 번호 30
  • 슬라이드 번호 31
  • 슬라이드 번호 32
  • 슬라이드 번호 33
  • 슬라이드 번호 34
  • 슬라이드 번호 35
  • 슬라이드 번호 36
  • 슬라이드 번호 37
  • 슬라이드 번호 38
  • 슬라이드 번호 39
  • 슬라이드 번호 40
  • 슬라이드 번호 41
  • 슬라이드 번호 42
  • 슬라이드 번호 43
  • 슬라이드 번호 44
  • 슬라이드 번호 45
  • 슬라이드 번호 46
  • 슬라이드 번호 47
  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 52: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

6 HEAVY METALS The mechanism of heavy metal toxicity poorly understood may bind to key -SH groups in active centers of enzymes again producing dysfunction in many organ systems can also produce hypersensitivity (nickel chromium gold and others type IV hepersensitivity) Metal chelation DMSA (lead arsenic mercury) Deferoxamine (iron) EDTA (lead) penicillamine (copper lead) BAL (lead arsenic mercury) Lead particularly toxic to the nervous system producing deleterious effects especially in children

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
  • 슬라이드 번호 7
  • 슬라이드 번호 8
  • 슬라이드 번호 9
  • 슬라이드 번호 10
  • 슬라이드 번호 11
  • 슬라이드 번호 12
  • 슬라이드 번호 13
  • 슬라이드 번호 14
  • 슬라이드 번호 15
  • 슬라이드 번호 16
  • 슬라이드 번호 17
  • 슬라이드 번호 18
  • 슬라이드 번호 19
  • 슬라이드 번호 20
  • 슬라이드 번호 21
  • 슬라이드 번호 22
  • 슬라이드 번호 23
  • 슬라이드 번호 24
  • 슬라이드 번호 25
  • 슬라이드 번호 26
  • 슬라이드 번호 27
  • 슬라이드 번호 28
  • 슬라이드 번호 29
  • 슬라이드 번호 30
  • 슬라이드 번호 31
  • 슬라이드 번호 32
  • 슬라이드 번호 33
  • 슬라이드 번호 34
  • 슬라이드 번호 35
  • 슬라이드 번호 36
  • 슬라이드 번호 37
  • 슬라이드 번호 38
  • 슬라이드 번호 39
  • 슬라이드 번호 40
  • 슬라이드 번호 41
  • 슬라이드 번호 42
  • 슬라이드 번호 43
  • 슬라이드 번호 44
  • 슬라이드 번호 45
  • 슬라이드 번호 46
  • 슬라이드 번호 47
  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 53: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

정리하면 간에 독성을 일으키는 물질과 기전을 알고 있다 신경계에 독성을 일으키는 물질과 기전을 알고 있다 폐에 독성을 일으키는 물질과 기전을 알고 있다 신장에 독성을 일으키는 물질과 기전을 알고 있다 면역시스템에 독성을 일으키는 물질과 기전을 알고 있다 태아에게 독성을 일으키는 물질과 기전을 알고 있다 암을 유발하는 물질과 기전을 알고 있다 유독가스와 기전을 알고 있다 미녀의 위험성을 알고 있다

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
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  • 슬라이드 번호 13
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  • 슬라이드 번호 41
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  • 슬라이드 번호 45
  • 슬라이드 번호 46
  • 슬라이드 번호 47
  • 슬라이드 번호 48
  • 슬라이드 번호 49
  • 슬라이드 번호 50
  • 슬라이드 번호 51
  • 슬라이드 번호 52
  • 슬라이드 번호 53
  • 슬라이드 번호 54
  • 슬라이드 번호 55
Page 54: Target organ toxicity - KOCWelearning.kocw.net/contents4/document/lec/2013/Chosun/J...3. TERATOGENESIS Thalidomide Developed as sedative and anti-nausea drug Causes birth defects in

밥은 먹고 다닙시다

  • 슬라이드 번호 1
  • 슬라이드 번호 2
  • 슬라이드 번호 3
  • 슬라이드 번호 4
  • 슬라이드 번호 5
  • 슬라이드 번호 6
  • 슬라이드 번호 7
  • 슬라이드 번호 8
  • 슬라이드 번호 9
  • 슬라이드 번호 10
  • 슬라이드 번호 11
  • 슬라이드 번호 12
  • 슬라이드 번호 13
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  • 슬라이드 번호 55