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Drug metabolism and drug toxicity

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image of Inflammopharmacology

Adverse drug reactions are a major problem for both health care providers and the pharmaceutical industry. They are a common and significant cause of morbidity and mortality and occasionally result in the withdrawal of an otherwise valuable therapeutic agent. There is now overwhelming evidence that adverse drug reactions are often caused by a metabolite of the drug rather than the drug itself, and that idiosyncratic susceptibility is due to interindividual variability in (1) the initial metabolism of the drug, (2) the body's ability to resist the toxicity through up-regulation of defence and/or repair mechanisms and (3) the degree and type of involvement of the immune system. This review focuses on well characterised examples of adverse drug reactions, with an emphasis on those involving analgesics, and attempts to show how innovative approaches to their investigation have revealed novel pathways and mechanisms underlying their biochemical basis. Such data may provide new targets for the development of drugs to treat or protect individuals from adverse reactions to commonly used therapeutic agents.

Affiliations: 1: Department of Pharmacology & Therapeutics, University of Liverpool, PO Box 147, Liverpool, Merseyside, L69 3GE


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