The therapeutic use of acetaminophen in patients with liver disease.
The therapeutic use of acetaminophen in patients with liver disease.
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DOI：
10.1097/01.mjt.0000140216.40700.95
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发表时间：
2005-03-01
影响因子：
4.2
通讯作者：
Tolman, Keith G
中科院分区：
文献类型：
--
作者：
Benson, Gordon D;Koff, Raymond S;Tolman, Keith G
多年来，对乙酰氨基酚已安全有效地用于控制所有年龄段患者的疼痛和/或发热。它通常被推荐作为各种患者和病症的一线治疗，包括老年人、病毒性疾病儿童以及骨关节炎、胃肠道疾病、出血性疾病、心血管疾病或肾脏疾病患者。然而，它的使用往往避免慢性肝病患者。对乙酰氨基酚应避免在这些患者中使用的观点源于对大量对乙酰氨基酚过量与肝毒性之间关系的认识，以及对肝病患者对乙酰氨基酚代谢缺乏了解。对乙酰氨基酚在慢性肝病中的肝毒性有多种理论机制，包括：代谢改变和谷胱甘肽储存减少，预计会增加肝毒性中间体N-乙酰基-对苯醌亚胺（NAPQI）的蓄积。然而，现有的对慢性肝病患者的研究表明，虽然对乙酰氨基酚的半衰期可能会延长，但在服用推荐剂量的患者中，细胞色素P-450活性不会增加，谷胱甘肽储存不会耗尽到临界水平。此外，对乙酰氨基酚已在各种肝脏疾病中进行了研究，没有证据表明在目前推荐的剂量下肝毒性风险增加。因此，对乙酰氨基酚可以安全地用于肝病患者，并且由于不存在与非甾体类抗炎药相关的血小板损伤、胃肠道毒性和肾毒性，因此是首选的镇痛剂/解热剂。
Acetaminophen has been used safely and effectively for many years to manage pain and/or fever in patients of all ages. It is commonly recommended as first-line therapy for a variety of patients and conditions, including the elderly, children with viral illnesses, and patients with osteoarthritis, gastrointestinal conditions, bleeding disorders, cardiovascular disease, or renal disease. However, its use is often avoided in patients with chronic liver disease. The perception that acetaminophen should be avoided in such patients arose from awareness of the association between massive acetaminophen overdose and hepatotoxicity, combined with a lack of understanding of the metabolism of acetaminophen in patients with liver disease. There are various theoretical mechanisms of acetaminophen hepatotoxicity in chronic liver disease including: altered metabolism and depleted glutathione stores that would be expected to increase accumulation of the hepatotoxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI). Available studies in patients with chronic liver disease, however, have shown that although the half-life of acetaminophen may be prolonged, cytochrome P-450 activity is not increased and glutathione stores are not depleted to critical levels in those taking recommended doses. Furthermore, acetaminophen has been studied in a variety of liver diseases without evidence of increased risk of hepatotoxicity at currently recommended doses. Therefore, acetaminophen can be used safely in patients with liver disease and is a preferred analgesic/antipyretic because of the absence of the platelet impairment, gastrointestinal toxicity, and nephrotoxicity associated with nonsteroidal antiinflammatory drugs.