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Drug idiosyncrasy - Part I

Pharmacogenetic variation has been identified in drug metabolism (acetylation, cytochrome P450 variants, plasma cholinesterase variants), inability to compensate for drug effects (G6PD, acute porphyrias) and in drug effects themselves (malignant hyperthermia). Each of the examples will be discussed separately.

Acetylator status

Acetylation is one of the non-microsomal phase II conjugation reactions. The gene controlling the enzyme N-acetyltransferase, exists in one of two forms that determines the acetylator status of an individual which can be slow or fast. The prevalence of slow acetylation is 60% in Caucasians and 10-20% in Asians. Drugs subject to N-acetylation include isoniazid, hydralazine, procainamide, some sulphonamides, sulphasalazine, nitrazepam, and caffeine. Slow acetylators are at higher risk of side effects of these drugs such as peripheral neuropathy with isoniazid, lupus syndrome with hydralazine and procainamide, allergic reactions and hemolysis with sulphonamides and gastroinstetinal side effects with sulphasalazine

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