Drayer D E, Reidenberg M M
Clin Pharmacol Ther. 1977 Sep;22(3):251-8. doi: 10.1002/cpt1977223251.
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.
本文综述了普鲁卡因胺、肼屈嗪、苯乙肼、异烟肼和柳氮磺胺吡啶药物乙酰化多态性的临床后果（治疗性和毒性）。与快速乙酰化者相比，遗传慢乙酰化者更易出现以下药物不良反应：（1）普鲁卡因胺诱导的抗核抗体更早出现；（2）普鲁卡因胺诱导的系统性红斑狼疮（SLE）更早且更频繁发生；（3）肼屈嗪诱导的SLE；（4）自发性SLE；（5）苯乙肼引起的嗜睡和恶心；（6）柳氮磺胺吡啶引起的发绀、溶血和短暂性网织红细胞增多；（7）异烟肼治疗后的多发性神经病。然而，异烟肼肝炎的发生率在快速乙酰化者中可能比在慢乙酰化者中更常见。与快速乙酰化者相比，遗传慢乙酰化者也更可能从相似剂量的以下药物中获得更大的治疗反应：苯乙肼、同时使用β受体阻滞剂时的肼屈嗪，以及采用每周一次治疗方案时的异烟肼。因此，了解患者的乙酰化表型有助于确定某些药物相关毒性和治疗反应的相对风险。
