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Pharma toxicology

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ppy by : Ma. Minda Luz M. Manuguid, M.D

ppy by : Ma. Minda Luz M. Manuguid, M.D

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    Pharma toxicology Pharma toxicology Presentation Transcript

    • 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
    • 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
    • definitions
      • Toxicology – the study of the adverse effects of chemicals on living things
      • Toxin – naturally derived, naturally exposed toxic chemical
      • Toxicant – manmade toxic chemical or of natural origin but manipulated, concentrated, or dispersed by humans
      • Poison – 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
    • 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
    • antidotes
      • Emetics – should be used only in conscious patients
      • Gastric lavage – except in corrosive poisons or in unconscious / convulsing patients
      • Chemical antidote – combines with the poison & inactivates it
      • Physiologic antidote – opposes the actions of the poison
      • Tannic acid in strong tea can precipitate Strychnine; Apomorphine, Cinchona alkaloids, Nicotine & Cocaine can neutralize Zn, Co, Cu, Hg, Ni, & Pb
    • 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)
    • 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 & Naloxone
      • Organophosphate effects
    • 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
        • LD 50 – dose that kills half of the experimental animal population
      • subacute / chronic toxicity
        • administration of multiple doses to detect any adverse effects
    • 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