Tolman K G
Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, USA.
Am J Med. 1998 Jul 27;105(1B):13S-19S. doi: 10.1016/s0002-9343(98)00070-9.
The central role of the liver in drug metabolism sets the stage for drug-related hepatotoxicity. The incidence of hepatotoxicity associated with non-narcotic analgesics is low, but their widespread use both prescription and over-the-counter-makes analgesic-associated hepatotoxicity a clinically and economically important problem. Hepatotoxicity is considered a class characteristic of nonsteroidal anti-inflammatory drugs (NSAIDs), despite the fact that they are a widely diverse group of chemicals. In fact, there are many differences in the incidence, histologic pattern, and mechanisms of hepatotoxicity between, as well as within, chemical classes. Most NSAID reactions are hepatocellular and occur because of individual patient susceptibility (idiosyncrasy). Aspirin, however, is a dose-related intrinsic hepatotoxin. Acetaminophen is also an intrinsic hepatotoxin but rarely demonstrates hepatotoxicity at therapeutic doses. It does cause hepatotoxicity with massive overdoses and with therapeutic doses in susceptible patients such as chronic users of alcohol. No hepatotoxicity has been reported to date with tramadol, another non-narcotic analgesic.
肝脏在药物代谢中的核心作用为药物相关肝毒性奠定了基础。与非麻醉性镇痛药相关的肝毒性发生率较低，但它们在处方药和非处方药中的广泛使用使得镇痛相关肝毒性成为一个在临床和经济上都很重要的问题。尽管非甾体抗炎药（NSAIDs）是一类化学性质差异很大的药物，但肝毒性被认为是它们的类别特征。事实上，不同化学类别之间以及同一类别内部，肝毒性在发生率、组织学模式和机制方面存在许多差异。大多数NSAID反应是肝细胞性的，并且是由于个体患者易感性（特异体质）而发生的。然而，阿司匹林是一种与剂量相关的内在肝毒素。对乙酰氨基酚也是一种内在肝毒素，但在治疗剂量下很少表现出肝毒性。在大量过量用药以及在易感患者（如慢性酒精使用者）的治疗剂量下，它确实会导致肝毒性。迄今为止，尚未有关于另一种非麻醉性镇痛药曲马多肝毒性的报道。
