Pharma toxicology
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Transcript of Pharma toxicology
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Toxicology
Minda Luz Meneses-Manuguid, M.D.
All substances are poisons. There is none which is not a poison. The right dose differentiates a poison & a remedy. - Paracelsus 1532
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definitions
Toxicology – the study of adverse effects on humans of prophylactic & therapeutic drugs, food & beverage additives, and industrial chemicals incorporated into consumer products
Poison – any compound which in relatively small quantities & by a chemical reaction can cause death or disability
Poisoning – may be accidental, suicidal, or criminal
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definitionsToxicology – the study of the adverse effects of chemicals
on living thingsToxin – naturally derived, naturally exposed toxic chemical Toxicant – manmade toxic chemical or of natural origin but
manipulated, concentrated, or dispersed by humansPoison – any substance which, when introduced into or
absorbed by a living organism, destroys life or injures health; any compound which, in relatively small quantities & by a chemical reaction, can cause death or disability
Antidote – medicine given to counteract the influence of poison or an attack of disease
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most common causes of Poisoning circa 1964
death Barbiturates Carbon monoxide Phenols; Cresols Methanol Ethanol Cyanide Arsenic fluoride Mercury salicylates
disability Ethanol Barbiturates Lesd Arsenic Salicylates Carbon monoxide Methanol Antihistamines Nonbarbiturate hypnotics phenothiazines
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antidotes
Emetics – should be used only in conscious patientsGastric lavage – except in corrosive poisons or in
unconscious / convulsing patientsChemical antidote – combines with the poison & inactivates itPhysiologic antidote – opposes the actions of the poisonTannic acid in strong tea can precipitate Strychnine;
Apomorphine, Cinchona alkaloids, Nicotine & Cocaine can neutralize Zn, Co, Cu, Hg, Ni, & Pb
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Chemical Antidotes
Dimercaprol / British Anti-Lewisite (BAL) Originally against Arsenic-containing lewisite
Effective vs. mercury, Arsenic, Antimony, Gold, Cadmium, Bismuth & Chromium
NOT effective vs. Silver, Lead, Selenium, Thallium
EthyleneDiamineTetraAcetic acid (EDTA)
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Mechanisms of Action: Antidotes
decrease absorption: emetics: Ipecac, activated Charcoal, mustard in warm water, CuSO4, Apomorphine 5mg subQ
neutralize the chemical: Iron & Deferoxamine; Paracetamol & N-acetyl Cysteine
enhance elimination: Salicylates & urinary alkalinization replace activity: Warfarin & vit K pharmacodynamic intervention: Heroin & NaloxoneOrganophosphate effects
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toxicity screening acute toxicity
administration of progressively larger single doses up to the lethal dose
“No-Effect” dose – largest dose at which a specific toxic effect is NOT seen
Minimum Lethal Dose – smallest amount of the drug that can kill a study animal
LD50 – dose that kills half of the experimental animal population
subacute / chronic toxicity administration of multiple doses to detect any
adverse effects
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toxicity screening
mutagenicity – detection of possible ability to induce
genetic alteration (mutation)carcinogenicity –
detection of possible ability to induce abnormal clonal uncontrolled proliferation of genetically altered cells
teratogenicity – detection of possible deleterious
effects on the developing fetus