Chitturi Shivakumar, George Jacob
Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW, Australia.
Semin Liver Dis. 2002;22(2):169-83. doi: 10.1055/s-2002-30102.
Hepatotoxic adverse drug reactions have contributed to the decline of many promising therapies, even among mainstream medication classes (bromfenac and troglitazone are recent examples). The spectrum of nonsteroidal anti-inflammatory drug-related liver toxicity continues to expand, with reports in children, interactive toxicity in persons with hepatitis C, and recognition of the toxicity of both the preferential and selective cyclooxygenase-2 inhibitors. Of the antihypertensive agents, methyldopa is now rarely prescribed and adverse effects are reported infrequently, whereas cases of liver injury associated with the angiotensin receptor and converting enzyme inhibitors are increasingly reported. Of the antidiabetic agents, acarbose, gliclazide, metformin, and human insulin have been implicated in causing liver injury. To date, the newer thiazolidinediones do not appear to share the hepatotoxic potential of troglitazone, although a few reports of acute hepatitis have accrued. Although liver injury has been associated with the "statins," the frequency of such toxicity is lower than that of the background population and the value of biochemical monitoring remains unproved. Newer concepts in anticonvulsant hepatotoxicity have been the recognition of the reactive metabolite syndrome, delineation of the risk factors for valproic acid toxicity, the potential role of carnitine in preventing valproic acid hepatotoxicity, and the toxicity of second-line antiepileptic drugs. Liver injury associated with newer psychotropic agents, particularly the selective serotonin reuptake inhibitors, is also discussed. The focus of the review is the hepatotoxicity of commonly used drugs with particular reference to recent and novel reports of toxicity. Well-known causes of liver injury such as chlorpromazine, phenytoin, and methyldopa are not discussed.
肝毒性药物不良反应导致了许多有前景的治疗方法的衰落,即使在主流药物类别中也是如此(最近的例子有溴芬酸和曲格列酮)。非甾体抗炎药相关肝毒性的范围不断扩大,有儿童病例报告、丙型肝炎患者的交互毒性以及对选择性和特异性环氧化酶-2抑制剂毒性的认识。在抗高血压药物中,甲基多巴现在很少被处方,不良反应报告也很少,而与血管紧张素受体和转换酶抑制剂相关的肝损伤病例报告越来越多。在抗糖尿病药物中,阿卡波糖、格列齐特、二甲双胍和人胰岛素都被认为可导致肝损伤。迄今为止,较新的噻唑烷二酮类药物似乎没有曲格列酮那样的肝毒性潜力,尽管有一些急性肝炎的报告。虽然肝损伤与“他汀类药物”有关,但这种毒性的发生率低于背景人群,生化监测的价值仍未得到证实。抗惊厥药物肝毒性的新概念包括对反应性代谢物综合征的认识、丙戊酸毒性危险因素的描述、肉碱在预防丙戊酸肝毒性中的潜在作用以及二线抗癫痫药物的毒性。还讨论了与新型精神药物,特别是选择性5-羟色胺再摄取抑制剂相关的肝损伤。综述的重点是常用药物的肝毒性,特别参考了最近和新的毒性报告。未讨论氯丙嗪、苯妥英和甲基多巴等众所周知的肝损伤原因。