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

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

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 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

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 & NaloxoneOrganophosphate 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

LD50 – 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