Drug Toxicology is the science that deals with the amount of an agent that causes an adverse action in some living system. The study of the effects of the body on the poison is toxicokinetics. The parent drug often causes the toxic effects. However, toxic effects may be resulting from the drug metabolites. Preclinical toxicity testing is a vital part of drug development. Preliminary toxicity testing typically uses LD50 and NOAEL, LOAEL values. With the information related to the Absorption, Distribution, Metabolism and Excretion, it is possible to predict concentration of toxin that reaches the site of injury and the resulting damage. The toxicology types are:
Ã¢â¬Â¢ Allergic responses
o Type I hypersensitivity reaction
o Type II antibody-mediated cytotoxic hypersensitivity
o Type III immune complex-mediated hypersensitivity
o Type IV delayed-type hypersensitivity
Ã¢â¬Â¢ The receptor mediated, ion channel and enzyme-mediated toxicity.toxicity.
Ã¢â¬Â¢ Enzyme mediated toxicology
Ã¢â¬Â¢ Organ directed toxicity
The main causes of drug toxicity/side effects are:
a. the predictable
b. the less predictable
c. the unpredictable
a. The predictable: excessive action at a primary site (overdosage). E.g. anaesthetics, warfarin
o non-selectivity: acting at unrelated sites (more likely with overdosage). E.g. chlorpromazine
o incomplete selective toxicity: acts against the host as well as the target organism or cell.
E.g. inhibitors of protein synthesis, antimicrobials, antifungals
o tolerance (dependence & abuse potential). E.g. opioids, benzodiazepines
o unavoidable side-effects. E.g. immunosuppression by corticosteroids Ã¢â¬â opportunistic infections
b. The less predictable: Genetic susceptibility (including species and strain differences
c. The unpredictable: untoward adverse reactions The prevention of the toxicity is based on knowledge of molecular mechanisms of toxin action.
Last date updated on June, 2014