SYMPTOMS ASSOCIATED WITH DRUG ABUSE OF OPIOID ANALGESICS USE AS A NON MEDICAL SUBSTANCE

TERM PAPERS PHARMACEUTICAL

by:

FACULTY OF MEDICINEUNIVERSITAS WIJAYA KUSUMA SURABAYA2014

CHAPTER I INTRODUCTION

Drug abuse is the use of drugs that can lead to a state that is not possessed by individuals and conducted outside of medical supervision, or which can cause a dangerous situation / threaten society (1).In the United States, the problem of drug abuse tops the causes of preventable disease (Prevent-able illness) and mortality. Each year, more than 500,000 deaths or 1 of 4 deaths related to drug misuse within the last 15 years (1992-2007) (2). Opioid analgesics are a group of drugs that have properties such as opium. Particularly opioid analgesics used to relieve or eliminate pain, although it also shows various other pharmacodynamic effects. The term is often used narcotic analgesics used for this group of drugs, but because this class of drugs can induce analgesia without causing sleep or decrease the term narcotic analgesic awareness becomes less precise. (3)The number of prescriptions for opioid analgesics have increased substantially over the past decade (4,5). In the U.S., opioid analgesics are the most commonly prescribed drugs in 2009, to 202 million prescriptions (6). Coinciding with the increased use of opioids, prescription opioid abuse has become a significant public health problem (7, 8, 9). In 2010, there were 2 million new patients for nonmedical use of prescription opioids in the United States, a figure that surpassed all other substances of abuse with the exception of marijuana (10). Along with the increasing misuse of prescription opioids, there has been a large increase in the number of substance abuse treatment admissions for prescription opioid addiction. (11)The problem of drug abuse is a serious concern of all parties. President through the Presidential Instruction No. 6/1971, about overcoming the trafficking and abuse of drugs such as morphine, heroin, drugs containing opium and smoking marijuana. Laws governing these substances is clear, namely Law No. 9, 1976 relating to narcotics. (2) In the Narcotics Act, which is classified as a narcotic marijuana, cocaine, and opioids / opiates. While that includes the type opiates are morphine and heroin. Drug abuse among teenagers increasingly difficult to stop. As a result, over the last decade in this country have discovered hundreds of thousands of drug addicts and other addictive substances. (2)This study aims to determine the symptoms that result from abuse of opioid analgesics in non-medical.1.1. Research Objectives To know the symptoms caused by drug abuse associated with the use of opioid analgesics as non-medical substance

1.2. Problem Formulation 1. Symptoms that can be caused by any misuse of opioid analgesics as non-medical substance? 2. How treatment of opioid analgesic abuse as non-medical substance?

CHAPTER IILITERATURE REVIEW

2.1. Pharmacy - Pharmacology Physical properties - Chemical Opium or opium is papaversomniferum L sap that has been dried.Opium is chemically divided into two groups: 1. The Group fenatran: morphine and codeine 2. Benzilisokinolin Group: noskopin and paparin On the basis of how it works these drugs can be divided into four groups: 1. The full agonists (strong) 2. Partial agonists (agonists weak to moderate) 3. Mixed agonist and antagonist 4. AntagonistsStrong opioid agonist class only has the effect of agonists whereas partial agonists can cause agonist effects atu as antagonists with potent agonist of the bond shift in opioid receptor and reduces its effect. Opioids are a mixture of opioid agonists and antagonists are agonists that have an effect on the opioid receptor subtypes and as a partial agonist or antagonist at other receptor subtypes. Based on the formula in the opioid class of drugs awakening to be derivatives venantren, venil hepilamin, phenyl piperidine, morfinan and benzomorfin. (Pharmacology UI case 211)

General Pharmaceutical Preparation containing a mixture of alkaloids in rough shape for example pulvus opii containing 10% morphine and codeine is less than 0.5%. Pulvus Doveri containing 10% pulvus opii the status of 150 mg containing 1.5 mg pulvus Doveri mofin. Preparations containing pure alkaloids can be used for oral or parenteral administration. Commonly used is the HCl salt, sulfate salt, or phosphate morphine alkaloid with levels of 10 mg / ml. Codeine is available in the free base or the hydrochloride salt form. One tablet contains 10, 15, or 30 mg of codeine. (Farmako UI case 218)

General PharmacologyOpioids are analgesics that reduce pain juice, aggression and sexual desire. These substances also cause respiratory depression, miosis, bradycardia, a decrease in tension, obstipation, feeling dizzy and fall of body temperature. The emergence of comfortable or euphoria juice occasionally caused by the loss of a great pain. (Essential drugs case 364)

Indication Pain: myocardial Infrak, neoplasms, pneumothorax spontant, trauama eg burns, fractures Cough: cough reflex inhibits unproductive Acute pulmonary edema: morphine intravenously to parse shortness of breath due to pulmonary edema accompanying left heart failure. antidiarrheal: alkoloid morphine useful for stop diarrhea by direct effect on intestinal smooth muscle. (Farmako UI case 216)

Contra indications Impaired liver function Impaired renal function Pregnant women

Side effects (essential drugs case 349) Suppression CNS: hypotermia, mood changes, nausea, vomiting, delirium. Channels breath: bronchokontriksi, breathing becomes more shallow and the frequency decreases. The circulatory system: peripheral vasodilation, hypotension occurred at high doses and bradycardia. Gastrointestinal tract: reduced motility (opstipasi). Channels Urogenital: urinary retention due to increased tone of the bladder spingter

2.2. Pharmacodynamic (UI Farmako case 231)Effects of morphine occurs in the central nervous system and organs containing smooth muscle. Effects of morphine on the central nervous system has two properties, namely depression and stimulation. Depression is classified analgesia, sedation, emotional changes, alveolar hypoventilation. Including stimulation of parasympathetic stimulation, miosis, nausea, vomiting, hyper active spinal reflexes, convulsions and secretion of anti-diuretic hormone.Morphine can cause respiratory depression in primary

Mechanism of actionThe main effects of opioid receptor activation is lowered neurotransmission. The decrease neurotrasnmisi can occur due to inhibition of presynaptic release of neurotransmitters (acetylcholine, dopamine, norepinephrine, substance P), and sometimes also occur seizure inhibition in post-synaptic activity. Biochemical events initiated by the binding of opioid receptors by opioid agonists is characterized by an increase in potassium conductance (which causes hyperpolarization), calcium channel inactivation, or a combination of both. Such a process would lead to a sudden decrease in the release of neurotransmitters. Adenyl cyclase inhibition mediated by opioid receptors do not play a role in the rapid effects of opioids, but most likely this mechanism plays a role in the slow effect through decreased response of cyclic adenosine monophosphate neuropeptidea gene(CAMP) and a decrease in the concentration of neuropeptide messenger (messenger) RNA / m-RNA.Opioid receptors located in the peripheral end of the primary afferent neurons and activation of these receptors causes a decrease in inhibitory neurotransmission or release of neurotransmission processes of excitation, such as substance P. With these considerations, it is injected intra-articular morphine (3 mg) may provide longer analgesia although the procedure has been completed artoskopi knee. Cholinergic transmission in the CNS depression caused by inhibition of the release of acetyl-choline from nerve endings play an important role in the analgesic effect and side effects of opioid agonist drugs. Opioids do not affect the level of response in the afferent nerve endings to noxious stimulation. Opioids also does not interfere with the conduction of nerve impulses along peripheral nerves.

2.3. PharmacokineticsAbsorption, distribution, metabolism, and excretion (ADME commonly known as) is an important feature of apapun.Penyerapan oral opioid medications vary widely. Morphine is not absorbed when given orally regularly, so it is usually injected morphine intravenous or intramuscular (IM) (12). Most substances have the effect of oral opioids slow release, given to patients with chronic pain, where patients are not allowed to swallow or chew the substance directly in order to avoid overdose or poisoning. Codeine is well absorbed in oral administration, and is usually used as a cough suppressant. Most opioids work secata metablisme maximum on the first pass, which plays a role in the metabolism of the liver, and has a weaker absorption than IV or IM administration. (12,13)Absorption of opioids in the organs vary widely. Although each type of opioids have different affinities to the protein, opioids can quickly leave the blood compartment, and then assembled into tissues that have a high blood perfusion such as brain, lung, liver, kidney and spleen. (15) The concentration of opioids and muscle is actually smaller, but the muscle tissue has a large volume of so many who accumulates there. Although blood flow in fat tissue is low, but the accumulation of fat tissue is an important thing because there will be a redistribution back by opioids well with fat-soluble, such as fentanyl. (15,16)Most of opioids will be converted into more polar metabolites largely glukoronid, which will then be excreted through the kidneys. For example morphine, most will conjugated to morphine-6-glukoronid, an effect that has kompenen neuroeksitatori. Neuroeksitatori effect is not mediated by opioid receptors but rather by the GABA system / glisinergik. Approximately 10% of morphine is converted into M6G, an active metabolite of the analgesic effect of 4 to 6 times more potent than morphine. But the more polar metabolites have limitations to penetrate the blood-brain barrier. Excessive accumulation of this drug as in patients with renal failure or the use of large doses will certainly cause many side effects. Seizures due neuroeksitasi effects of M3G and employment effects of prolonged opioid produced by M6G. (3,4,5,8) (15)Ester groups such as heroin and remifentanyl rapidly hydrolyzed by tissue esterase. Heroin (diasetilmorfin) hydrolyzed to monoasetilmorfin and ultimately into morphine which is then conjugated by hepatic oxidative glukoronat.Metabolism acid is the primary route of degradation of opioids such as meperidine group fenilpiperidin, fentanyl, alfentanyl and sufentanyl. Results methylated metabolites of meperidine is normeperidin may accumulate in patients with decreased renal function or the use of high doses. Normeperidin can cause seizures when accumulated in high enough quantities. Instead fentanyl has no active metabolites. P450 isozymes CYP3A4 metabolizes fentanyl through the N-dealkylation in the liver. CYP3A4 is also found in the small intestine mucosa and contribute to the process of first-pass metabolism when fentanyl is administered orally. Codeine, oxycodone, and hydrocodone are metabolized in the liver by the P450 isozyme CYP2D6 which will produce metabolites with greater effect. For example, methylated codeine into morphine. (15)Polar metabolites, including conjugates glukoronid of opioid analgesics, mostly excreted through small urin.Sejumlah of parts that are not converted can also be found in urine. In addition glukoronid conjugate was also found in the bile, but enterohepatic circulation only a small role in the process of excretion. (4)The half-life of most derivative of morphine that is administered orally is 3 to 6 hours, although some classes of first-pass liver metabolites (after glucuronidation) still has an analgesic effect is quite large. Morphine is not metabolized by both the neonate and the relatively long acting in causing respiratory depression, so it should not be used during childbirth, where meperidine is a safer option.Respirasi refundable with opioid antagonist naloxone, as required. (1,2,3)For postoperative or chronic pain, opioids have been used for the controlled analgesia pump control pasien.Pasien that increase or decrease the dose to control pain but minimize the effects of this penenang. These pumps generally do not lead to excessive treatment and dependency are widely feared by patients. (14)Stereospecific interaction with opioid receptor protein in certain cell membranesel ssp, on peripheral nerve endings and the cerna.Efek duct cells is mediated by the four main opioid receptor family Stereospecific interaction with opioid receptor protein in certain cell membranesel ssp, on peripheral nerve endings and the cells of the gastrointestinal tract. Primary effect is mediated by the opioid receptor family 4 as indicated by the ancient Greek letters , , and . In general, bond strength correlates with analgesia. Analgesic properties mediated by receptors, but receptors in the dorsal horn also support a more selective enkephalins interact with receptors on peripheral . kurang specific receptors, this receptor also binds non-opioid drugs such as halusinogenfensiklidin. (16) Distribution of high density of opioid receptors located on five general areas ssp known to be involved in integrating the formation of pain. The road down from periaquaduktus gray (PAG) to the spinal cord dorsal horn. This receptor was identified in peripheral also can. (16)2.4. ToxicityToxidrome (a syndrome that is caused by the presence of toxins in the body) is a classic of opioid intoxication include apnea (a condition of suspension of external breathing), fainting (syncope) and miosis.Sine qua non (condition, or a sign that the findings would not likely be present in the absence of disease or suspected condition) in opioid poisoning is the presence of respiratory depression. Dosing of opioid therapy in a person without causing a decrease in respiratory activity tolernasi the drop rate depends on the level of the dose given. Decreased respiratory symptoms are the most easily observed and its peak is apnea. 12x/menit respiratory rate or less on a person with a sleep condition that is not being clearly showed the presence of physiological acute opioid poisoning especially when accompanied by miosis or stupor. The presence of miosis alone is not sufficient to infer the presence of a diagnosis of opioid poisoning. (17,18)Ingestion of many substances can produce mydriasis and pupillary reaction normalization, as it can also cause poisoning of meperidine, propoksifen or tramadol. Instead of an overdose of opioids, anticonvulsants agent and agent-hipnotif other sedatives can cause miosis and coma, but generally without respiratory depression. Oxygenation failure was defined as an oxygen saturation less than 90% while the patient inhales ambient air and with adequate ventilation to achieve normal carbon dioxide tension (partial pressure of carbon dioxide) is often caused by pulmonary edema. Pulmonary edema can be caused by several conditions. One possible cause is an inspiration occurs in a closed glottis, causing a pressure drop intraaortik and further causing fluid extravasation. Or other possible cause is the presence of acute lung injury that may result from a mechanism similar to that postulated for neurogenic pulmonary edema. In this scenario, vasoactive sympathetic response to stress in a person who has recovered from the condition of intoxication leads to leakage of peripheral lung. Hypothermia may occur due to the absence of a persistent response in a cold environment or due to errors in the recovery effort opioid intoxication patients by immersing in water. Besides someone who fainted opioid-induced rhabdomyolysis can experience, renal failure and compartment syndrome myoglobinurik. Other laboratory abnormalities that may occur is in conjunction with the aminotransferase concentration of liver injury caused by paracetamol or hypoxemia. Seizures associated with tramadol overdose, propoksifen and meferidin. (17,18,19)OVERDOSE DIAGNOSISHipopnea presence or apnea, miosis, and fainting should direct the physician to suspect the possibility of a diagnosis of opioid intoxication which may be inferred by observing physical signs, medical history and physical examination. In patients with severe respiratory depression, recovery ventilation and oxygenation takes precedence over the patient's medical history or obtain physical examinations or diagnostic tests. (20)Once the patient's condition is stable, doctors should ask all who have ever used opioid analgesics, paracetamol and other drugs and dangerous and ask if the patient has contact with anyone who receives the treatment of chronic pain or dependence. In the physician must perform a physical examination to evaluate the size and reactivity of pupils and respiratory rate and auscultation findings that lead to pulmonary edema. Patient must completely naked to find a possible patch fentanil.The doctors also should do muscle palpation, cohesiveness, swelling and tenderness which becomes characteristic of compartment syndrome. Finally, plasma levels of paracetamol should also be determined, to see the possibility of paracetamol hepatotoxicity. (20) Qualitative urine analysis is needed to see the possibility of the use of illegal drugs. But the discovery of the existence of the use of illegal drugs will not significantly affect the decision of the action to be taken, this is because the therapy is basically not too different opioid overdose. (21)OVERDOSE TREATMENTPatients with apnea requiring mechanical and pharmacological stimuli. For patients who collapsed with respiratory rate 12x/menit or less ventilation should be provided with a bag-valve mask; chin-lift and jaw-thrust should be made to ensure that the anatomical position helps to reduce hypercarbia. Although the relationship between the partial pressure of carbon dioxide and acute lung injury is not clear, provide adequate ventilation is a simple response that is beneficial to restore oxygenation and prevent sympathetic surge that can trigger pulmonary edema after restoration of apnea with minimal risk. (17,18)Naloxone is one antidote for an overdose of opioid mu receptor antagonist that competitively reversing all the signs of opioid overdose. Naloxone will be active when administered via the parenteral route, intranasal or pulmonary. In patients with opioid dependence, initial plasma concentrations of naloxone should be lower because of the higher volume of distribution and elimination half-life is longer than the patients who did not experience apioid dependence. Onset of action of naloxone is less than 2 minutes in adults when administered by intravenous injection, the duration of action of approximately 20-90 minutes clear, a shorter work period compared to most opioids. (20,21). Naloxone dose is empirical. The effective dose is highly dependent on the amount of opioid analgesic that is accepted by the patient, the relative affinity of naloxone in opioid analgesics position on ties with mu receptors, the patient's weight and the level of penetration of the analgesics on the central nervous system. Because most of the information is not known, then to determine the effective dose depends heavily on experimental therapies. The initial dose of naloxone for adults is 0.04 mg, if no response dose should be increased every 2 minutes, maximum dose of 15 mg. If there is no reduction in symptoms of respiratory depression after administration of 15 mg naloxone, this means that cause respiratory depression is not an opioid overdose. Return of opioid toxicity following administration of a single dose of naloxone are often transient, recurrent respiratory depression is indicative of the need for continuous infusion. (21) Naloxone can be administered without the need to worry about including in patients with opioid dependence. Concerns that the naloxone will harm patients with opioid dependence unwarranted. The signs are not as exciting as yawning, lacrimation, piloerection, diaphoresis, myalgia, nausea, and diarrhea may occur but it was not life-threatening. In addition patients with opioid tolerance often have an inadequate response to naloxone to increase respiratory rate. After the respiratory rate increased after the administration of naloxone patients should be observed for 4-6 hours before finally giving naloxone was discontinued. (21)Alternative methods for the administration of naloxone is via intratracheal intubation, a procedure that ensures the safety of administration in conjunction with oxygenation and ventilation procedures. Patients who experience opioid intoxication due to the use of long-actingatau formulation of extended-release can experience recurrent respiratory depression or require intravenous naloxone or intratracheal intubation performed emergency tagging on equipment. (21)Once the patient's condition, must be investigated further and confirmed that the patient's body surface there fentanyl patch. Fentanyl patches often cause intoxication delayed. Axilla, perineum, scrotum and oropharynx should be inspected and if found fentanyl patches should be removed and the skin should be decontaminated with cold water and sabun.Pada patients may swallow the fentanyl patches should be irrigated with polyethylene glycol to accelerate the elimination of the patch. (20,21)The presence of persistent hypoxemia after administration of naloxone may indicate the presence of negative-pressure pulmonary edema. In cases of mild hypoxemia supportive care alone is sufficient, but in severe cases required intubation administration orotrakeal and positive-pressure ventilation. Resolution of lung injury can be performed with aspiration of gastric contents is usually done within 24 hours. Because of the possible causes of lung injury is not due to excess fluid then the reduction of intravascular volume by using diuretics is often ineffective and may even worsen the condition myogloburik kidney failure, if any. Naloxone has been mistakenly regarded as the cause of pulmonary edema. However, in cases of fatal opioid overdose, pulmonary edema is almost always the case, including in the case before the development of the latest nalokson. The research have shown that pulmonary edema does not develop in patients who receive large doses of naloxone and by means of a continuous infusion. Finally, auscultation signs of pulmonary edema which is often not clear in patients with apnea, it became clear after the administration of naloxone. (20,21) Rhabdomyolysis is defined as a condition in which the concentration of creatinine-kinase or five times higher than the normal range of the last to be treated with fluid resuscitation to prevent precipitation (precipitation) of myoglobin in the renal tubules; bicarbonate does not improve the condition. Patients with compartment syndrome should have to accept emergency consultation for possible surgical fasciotomy. (5). Patients with hypothermia may require immediate warming. Increased aminotransferase concentrations, the presence of paracetamol in the blood, or both indicate the possible need for treatment with acetylcysteine. Ultimately necessary to identify the cause of overdose to determine appropriate follow-up care for these patients (20,21)

CHAPTER IIIRESEARCH3.1. Previous study of another persona. Adolescents are a group at high risk for drug abuse, and can cause a dangerous situation / threaten people. This cross-sectional study aims to determine the rate and risk factors of drug abuse among high school students (SMU). Respondents include 210 students from seven high schools in the city of Pekanbaru. Drug Abuse Screening Test (DAST-10) was used to measure the level it drug abuse and risk factors was obtained through questionnaires completed by respondents. The study showed that 67.2% of respondents are not problematic in drug abuse. There is a significant relationship between sex, stay at while parents, academic achievement, having friends who smoke and following extracurricular activities to the level of drug abuse. From the logistic regression analysis showed that the factor of residence (OR = 3,969, p = 0.002), followed ekstrakurile activity (OR = 0316, p = 0.001) and smoking (OR = 0.227, p = 0.001) were risk factors for drug abuse. (22)b. Opioid abuse increased in number from time to time and has the potential to cause physical disorders and comorbid mental disorders. A variety of common mental disorders such as depression, anxiety disorders, psychotic disorders, paranoid disorders, and others. Subjects were assisted intravenous opioid user group outreach program Bandung Ark Foundation is willing to be the subject of research, and not currently undergoing a rehabilitation program. This study was conducted in London between the months of May to August 2006, is a descriptive-cross sectional analysis. Subjects were interviewed using the Addiction Severity Index (ASI) is an instrument for measuring the degree of opioid dependence. Subjects consisted of 70 respondents; 35 people (50%) experienced mild dependence, 25 (35.71%) and the weight of 2 people (2.86%) is very heavy. All subjects were in the age group between 20-38 years old young adults. Gender subject of most of the male (95.71%). A significant association between depression (p = 0.035), state anxiety (p = 0.05), a state hostile / suspicious (p = 0.031), the problem of reality testing (p = 0.025) on the status of opioid users intravenous opioid dependence. The need for increased treatment in accordance with the status of opioid dependence (p = 0.000). This is a good situation because it can be used as a starting point for the treatment and rehabilitation of intravenous opioid users. Further research needs to be conducted to find the factors that cause dependence and the right approach to help users of intravenous opioids to want treatment. (23)

CHAPTER IVDISCUSSION

Drug abuse is a way to use the drug only for personal enjoyment or sects. This drug is a drug that can cause effects that happy feelings (euphoria) which usually can make opium. That caused by the influence of drugs is seen in how likely the drug will make the wearer become addicted. The stronger the drug, the more likely users become addicted. 4 Physical dependence is a biological phenomenon. Physical dependence is manifested by compulsive drug-seeking habits that people use repeatedly for personal satisfaction. Physical dependence is present when the drugs produce withdrawal symptoms and signs opposite to that expected. Addiction is usually used for the merger between the physical and physical dependence. 5 Opioid analgesic drug which is often misused heroin, Morphine, Oxycodone, Meperidine, Fentanyl.a. Heroin Heroin is an opioid drug that is often abused. The use of heroin can cause effects of warmth, and a high sense of pleasure that is often associated with sexual life. After injecting heroin effect will start a few minutes later. Heroin has a high solubility of the fat, which is made to pass through the blood-brain barrier rapidly. Having experienced an intense euphoria for 45 seconds to a few minutes, there was a period of tranquility for one hour. The effects of heroin disappears after 3-5 hours depending on the dose taken. Once addicted, users can consume 2-4 times per day. The effects of heroin up and down between "pleasure" and felt pain after withdrawal (period when the homeostatic decline due to the lack of the drug). This imbalance causes many problems from the homeostatic system is partly regulated by endogenous opioids. For example, the hypothalamic pituitary-gonadal-axis and the hypothalamic-pituitary-adrenal becomes abnormal in heroin users. Women heroin users will experience abnormal menses, and he will have a high sexual desire. Mood also be affected. 4In the central nervous system, repeated use can cause the following effects. 6 sensation of pain consists of malicious input coupled reaction of the organism to the stimulus. Analgesics on opioids may alter the patient's perception of pain and reaction to pain. This drug may also cause an increase in pain threeshold. However, the effect can only be inferred from the patient's subjective effects. EuphoriaPatients will also experience a sensation usually fun and free from worry. However, in normal patients (feel no pain), experience dysphoric effects may be more pronounced than fun. Dysphoria will cause fatigue and feeling unwell. SedationDrowsiness or blurring of thinking common in this type of drug delivery coupled with damage to the ability of logic. Sometimes it can also happen a little amnesia. Though sleepy patients more easily aroused. However, the combination, orfin with other central depressant drugs, may result in a deep depression. Morphine is an analgesic drug that can disrupt sleep patterns of REM and NREM, as well as other opioids drugs.

Depression of respiration Drugs of this type would inhibit the respiratory mechanism in the brain stem. Alveolar CO2 pressure may also be increased. cough suppressants Drugs of this type can perform on the suppression of the cough response. Codeine, one type of drug, often used in people who suffer from pathological cough and patients who require the maintenance of ventilation through an endotracheal tube. However, cough suppression can also lead to accumulation of secretions which will menhambat airway and atelectasis. Miosis a pharmacological action that have little or no tolerance at all. Therefore, it is important in the diagnosis of overdose opioids.Pupil constriction will usually appear in patients who addict. It is believed to be due to the activity of this drug in the spinal cord. It also can cause the piston so that the ventilation was also disrupted. Analgesic opioids can activate the chemoreceptor trigger zone in the brain stem that trigger vomiting and nausea.

b. MorphineMorphine is produced from opium or opiate raw and an opium alkaloids contained in the form of a white powder. Morphine consumption is usually done by inhaled or injected. Because morphine is classified as a depressant type, then it works by pressing the central nervous system, cause a decline in the activity of neurons, dizziness, feelings and consciousness change periodically. Continuous morphine consumption has led to a high risk of death.Physical characteristics withdrawal symptoms caused by morphine: Colds, runny nose sneeze Body temperature increased sharply Nausea Vomiting Diarrhea InsomniaIf not given morphine would cause physical pain including muscle pain and stiffness in the back, legs, until the entire body is accompanied by anxiety, convulsions small, and weak. Symptoms can be found within 6-8 hours, with peak symptoms will occur on day 2 or day 3. The duration of the physical pain will be a state of withdrawal usually lasts between 7-10 days.c. OxycodoneOxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. Oxycodone oral medications are generally prescribed to relieve moderate to severe pain. Currently formulated as single ingredient products or product added. Some common examples of compounding are oxycodone with acetaminophen / paracetamol or NSAIDs such as ibuprofen. These formulations are available as generics but are also made under various brand names.Oxycodone can be taken orally in tablet form, the drug is a drug of choice for pain morphine substitute medium to severe. Oxycodone is generally used for pain caused by joint dislocations or fractures, as well as effective in treating pain after surgery and childbirth. Oxycodone addiction effects smaller than morphine and heroin (24)

d. MeperidineMeperidine / Demerol is a pain reliever compound level below the narcotic morphine and includes supervised use. Such as morphine, meperidine works by occupying the 'post office' where the information about the arrival of pain, either from inside or outside the body, to be delivered to the brain. With the occupation, the recipient is no longer in pain medicine because there is no more information is conveyed to the brain. These drugs are generally used in the form of injection to overcome severe pain, such as pain during childbirth. Provision should be accompanied meperidine careful attention to the patient, because these drugs, even in therapeutic doses, can lead to inhibition of the respiratory system and the cessation of heartbeat. Meperidine is not recommended for use in the long term and in large doses as a result of metabolism in the liver, normeperidin, can accumulate in the body and cause tremors, twitching, and even seizures. These side effects are also caused meperidine rarely used as the drug of choice among opioid painkillers other groups.e. FentanylFentanyl is a drug which is a narcotic pain reliever. Fentanyl buccal tablets are used to treat cancer pain that can not be controlled by other drugs. This drug does not treat the pain not caused by cancer, as usual headaches or back pain. Fantanyl buccal also be used for other needs that are not listed here.Fentanyl Side Effects Itching with red spots Difficulty breathing Swelling of the face, lips, tongue or throatDiscontinue use if there fentanyl following serious side effects: Weak, shallow breathing severe fatigue, drowsiness Skin moist, cold Head feels light or faintOther side effects: Nausea, vomiting, abdominal pain, constipation Dizziness, drowsiness, headache Swelling Pain or inflammation of the mouth where the tablets are givenFentanyl buccal tablets are used to treat cancer pain that can not be controlled by other drugs. This drug does not treat the pain not caused by cancer, as usual headaches or back pain.Fentanyl is not good to use for people who are using MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within 14 days. Fentanyl is the generic name of Fentanyl (buccal) and brand names are Fentora, Onsolis.Common Side Effects Morphine and other opioida cause a large amount of unwanted ES, namely: suppression of CNS: eg sedation, respiratory and suppress coughs, miosis, hipothermia, and swings the soul (mood). As a result of direct stimulation of the CTZ (Chemo Trigger Zone), nausea and vomiting arise. At higher doses result in decreased mental activity -gastrointestinal tract: reduced motility (obstipation), contraction of sphincter gallbladder (stone-biliary colic). channel-Urogenital: urinary retention, decreased uterine motility (extended delivery time). airways: bronchoconstriction circulatory system: vasodilatation, hypertension, bradycardia custom: the risk of addictionHabits and AddictionPhysical dependence is for long-term use in most consumer habits and cause dependence. The cause may be due to reduced resorption opioids or overhaul / elimination is accelerated, or due to decreased tissue sensitivity. The drug becomes less effective, requiring higher doses to achieve the original effect. This is called tolerance.Psychological dependence that is going to effect the mental needs psikotrop (euphoria, a sense of comfort and fresh) can be an advanced very strong, to the patient as if forced to continue using the drug.Abstinence symptoms always occur when drug use is stopped (abruptly) and the original can be evaporated, great sweat and tears, restless sleep, and feeling cold. Then arises vomit-munath, diarrhea, tachycardia, mydriasis, tremors, muscle spasms, blood pressure rises, which can be accompanied by severe psychological reactions (anxiety, irritability, worries die).These effects cause why people with difficult patients who are already addicted to halt all use opiad. In order to avoid the bad effects of this, they are "forced" to continue its use.There are strong indications that the occurrence of tolerance and dependence is closely related to the activation of the dopaminergic system in the brain. All of addiction to substances that are efficacious in acute increases the amount of dopamine, which is associated with eufori effects, emotional lability, confusion and hysteria, for example, the abuse of morphine. trigger the release of dopamine, while cocaine blocks the reuptake of more than ten other neurotransmitters noradrenaline and serotonin whom also play a role in addiction but the effect is much lighter. Dopamine levels that are too high can cause hallucinations and psychosis akut.dimana hallucination is a sensory experience (sensory perception) in the absence of sensory stimulation (sensory stimulation)., And in the case of abuse of opioid analgesics (morphine which most often is) used to receive the body of a peptide exogenous (morphine) without a clinical indication that the body responds by not generating an endogenous peptides (eg, endorphins) that will be discontinued if the use of morphine endogenous peptides would not be formed, because accustomed supplied from outside the body, so it can happen dependence.Opioid addiction treatment is primarily aimed at two aspects, namely the cessation of use (withdrawal) and social rehabilitation of the patient. In the treatment of a number of factors must be considered: o The level of physical dependence of patients o Patients should be given another drug (eg methadone) to suppress abstinence symptoms seriously while gradually reducing the dose (substitution therapy)In farmakotepeutis, a type of treatment that is more specific to eliminate the addiction to opiate analgesics based on the theory that when the receptor is inhibited by the opioid antagonist substances, the use of opiates will not cause a physical dependence. In this case, a specific opiate antagonist naloxone has been clinically tested but the results are much less satisfactory than metadon.naltrekson therapy is a pure morphine antagonist (without the agonist) can avoid opioida effects, such as euphoria these drugs are used as auxiliaries during the process of tackling addiction to support,, to stay clean. "should only be used on addicts who had not used drugs for 7-10 days. when opiates are used again within 15 minutes will appear serious acute abstinence symptoms and can last 48 jam.daya work lasts for 24-72 jam. Naltrexone dosage 50 mg per day or 3 times a week. Handling hooked done by the method of "cold turkey" in which the administration of narcotic substances to patients discontinued at once, although withdrawal symptoms arise great as abdominal cramps, diarrhea, vomiting, muscle pain, runny nose, watery eyes, cold sweats and chills .Therefore, the use of these drugs should be under the supervision of physicians and pharmacists. If not, the user will be hooked and will be referred to as "people who abuse drugs".TREATMENT PROGRAMME OR TREATMENT (ANTI DOTUM) Naloxone is a drug to counteract poisoning narcotics or opiates called antagonists. Other drugs to counter the influence of morphine or heroin is nalorphine, levallophan, cyclazocine, but the risk is quite dangerous. Naloxone can help quickly if it is given in the form of injections. The provision in the form of an injection of naloxone HCl (Narcan, Nokoba) which begins with a dose of 0.4 mg / dl, can improve the situation of respiratory disorders. Provision should go straight into a vein or intravenously. After the injection, note the state of breathing. If not improved, as can be observed within 3-5 minutes plus one ampoule is repeated again until the effect is achieved with a sustained response of consciousness, loss of respiratory depression, and pupil dilation.Drug abuse treatment program consists of two phases, namely: detoxification therapy Maintenance therapy (maintenance)Both of the above should be continuous therapy, for detoxification therapy alone is not a cure. After the patient passes through the critical phase, he has to stop its reliance through therapy program above. The increasing number of drug addicts is increasing. Medical cure for drug addicts often lead to relapse condition, again relapses. Patients undergoing detoksifiksi possible drug addiction in his home for 5 consecutive days. Additionally, for healing requiring maintenance therapy (maintenance). Especially for dependency opioida, required a special treatment program. Besides given drug therapy, therapy should be social, occupational therapy, or religious therapy. A holistic approach involves a team of professionals such as doctors / psychiatrists, nurses, psychologists, religious leaders, and social workers will provide satisfactory results. (9)

CHAPTER VCONCLUSION Opioid analgesics used in the treatment of pain caused by factors other than the presence of inflammatory mediators and in very severe pain that can not be addressed with non-opioid analgesics Drugs that opioid analgesics are often misused heroin, Morphine, Oxycodone, Meperidine, Fentanyl. Agonist opioids (methadone) is the best therapy in the treatment of opioid dependence. There needs to be awareness of all parties to prevent abuse of opioid medications (narcotics) can cause dependence.

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