Toxicology.pptVIP

Toxicology Prof. Neil Marrion DW2C N.V.Marrion@bris.ac.uk http://www.bris.ac.uk/depts/Pharmacology/intranet.htm * ‘All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.’- Paracelus (16th century physician-alchemist) ‘A poison is any substance or matter which, when applied to the body outwardly, or in any way introduced into it, can destroy life by its own inherent qualities, without acting mechanically, and irrespective of temperature.’ Toxicology is the science that deals with the amount of an agent that causes an adverse action in some living system. Acute poisoning accounts for 10-20% of hospital admission for general medicine. Factors influencing toxicity: Absorption oral sublingual injection (I.V., I.P., subcut, I.A.) pulmonary topical Metabolism Mainly liver (some in GI tract, kidneys, lungs) Phase I – introduce or expose a functional group on the parent compound – losing pharmacological effect Phase II – produces polar conjugates – generally inactive and easily excreted in urine and/or faeces 4. excretion Distribution binding – plasma proteins, tissue (liver, bone, fat) Factors influencing toxicity: All these factors determine the drug/toxin bioavailability plasma concentration – time curves Drug eliminated from a single compartment by a first order process half life ~ 4hrs If sample before 2 hrs, reveals drug elimination is a multiexponential process a steady-state concentration will be achieved when a drug is administered at a constant rate Factors influencing toxicity: drug absorption 10x as rapid as elimination can have the same relationship for cumulative toxicity Dosage (mg/kg) Therapeutic response % 100 50 ED50 Death 100 50 LD50 MED MTD ED50- dose which will be therapeutically effective in 50% of animals (median effective dose) LD50- dose which will, on average, kill 50% of animals in a population MED- minimum effective dose (the least dose that is likely to be effective). Also