Amarapurkar Deepak N
Department of Gastroenterology, Bombay Hospital and Medical Research Centre, New Prabhadevi Road, Prabhadevi, Mumbai 400 025, India.
Int J Hepatol. 2011;2011:519526. doi: 10.4061/2011/519526. Epub 2011 Aug 22.
Patients with decompensated liver cirrhosis have various serious complications which require multiple drugs for therapeutic or prophylactic use. Majority of the drugs are primarily metabolized and excreted by hepatobiliary system; hence, liver cell necrosis contributes to impaired drug handling in liver failure while portosystemic shunt can alter drug action in cirrhosis. Hence, in order to decide drug dosing in liver failure, 3 important factors need to be considered (1) pharmacokinetic alterations of drugs, (2) pharmacodynamic alteration of drugs, and (3) increased susceptibility of patients to adverse events particularly hepatotoxicity. Though there is no predictable test which can be used to determine drug dosage in patients with decompensated liver cirrhosis, drugs with first pass metabolism require reduction in oral dosages, for high clearance drugs both loading and maintenance dosages need adjustment, for low clearance drugs maintenance dose needs adjustment, whenever possible measuring drug level in the blood and monitoring of adverse events frequently should be done. No evidence-based guidelines exist for the use of medication in patients' with liver cirrhosis. There are hardly any prospective studies on the safety of drugs in cirrhotic patients. According to the experts opinion, most of the drugs can be used safely in patients with cirrhosis, but drug-induced hepatotoxicity may be poorly tolerated by patients with cirrhosis; hence, potential hepatotoxins should be avoided in patients with liver cirrhosis. Potentially hepatotoxic drugs may be used in patients with liver cirrhosis based on the clinical needs and when there are no alternatives available. Caveat for the prescribing medications in patients with cirrhosis the drug dosing should be individualized depending on a number of factors like nutritional status, renal function, adherence, and drug interaction. Monitoring of the liver function at frequent intervals is highly recommended.
失代偿期肝硬化患者有多种严重并发症,需要多种药物进行治疗或预防。大多数药物主要通过肝胆系统代谢和排泄;因此,肝细胞坏死会导致肝衰竭时药物处理受损,而门体分流会改变肝硬化时的药物作用。因此,为了确定肝衰竭时的药物剂量,需要考虑3个重要因素:(1)药物的药代动力学改变,(2)药物的药效学改变,以及(3)患者对不良事件尤其是肝毒性的易感性增加。尽管没有可预测的测试可用于确定失代偿期肝硬化患者的药物剂量,但有首过代谢的药物需要减少口服剂量,对于高清除率药物,负荷剂量和维持剂量都需要调整,对于低清除率药物,维持剂量需要调整,尽可能测量血液中的药物水平并频繁监测不良事件。对于肝硬化患者用药,不存在基于证据的指南。关于肝硬化患者药物安全性的前瞻性研究几乎没有。根据专家意见,大多数药物可在肝硬化患者中安全使用,但肝硬化患者可能对药物性肝毒性耐受性较差;因此,肝硬化患者应避免使用潜在的肝毒素。基于临床需要且无其他替代药物时,可在肝硬化患者中使用潜在的肝毒性药物。肝硬化患者用药的注意事项:药物剂量应根据营养状况、肾功能、依从性和药物相互作用等多种因素个体化。强烈建议定期监测肝功能。