Abstract

The clinical consequences (therapeutic and toxic) of drug acetylation polymorphism are reviewed for procainamide, hydralazine, phenelzine, isoniazid, and salicylazosulfapyridine. Genetic slow acetylators are more likely than rapid acetylators to experience the following adverse drug reactions: (1) earlier development of procainamide-induced antinuclear antibody; (2) earlier and more frequent development of procainamide-induced systemic lupus erythematosus (SLE); (3) hydralazine-induced SLE; (4) spontaneous SLE; (5) drowsiness and nausea from phenelzine; (6) cyanosis, hemolysis, and transient reticulocytosis from salicylazosulfapyridine; and (7) polyneuropathy after isoniazid therapy. The incidence of isoniazid hepatitis may, however, be more common in rapid than than in slow acetylators. Genetic slow acetylators are also more likely than rapid acetylators to experience greater therapeutic responses from similar doses of the following: phenelzine, hydralazine provided beta blockers are concurrently used, and isoniazid if once weekly therapy is used. Thus, knowledge of the acetylator phenotype of a patient can help determine the relative risk for some drug-related toxic and therapeutic responses.