Davies G, Kingswood C, Street M
University of Brighton, England.
Clin Pharmacokinet. 1996 Dec;31(6):410-22. doi: 10.2165/00003088-199631060-00002.
Patients with renal insufficiency commonly require the administration of an opioid analgesic to provide adequate pain relief. The handling of morphine, pethidine (meperidine) and dextropropoxyphene in patients with renal insufficiency is complicated by the potential accumulation of metabolites. While morphine itself remains largely unaffected by renal failure, accumulation, as denoted by an increase in both mean peak concentrations and the area under the concentration-time curve, of both the active metabolite (morphine-6-glucuronide) and the principal metabolite (morphine-3-glucuronide, thought to possess opiate antagonist properties) have been reported. The increased elimination half-lives of the toxic metabolites norpethidine and norpropoxyphene in patients with poor renal function administered pethidine and dextropropoxyphene, respectively, makes their routine use ill advised. Case reports of prolonged narcosis associated with the use of both codeine and dihydrocodeine in patients with renal insufficiency call for care to be used when prescribing these agents under such conditions. Although the pharmacokinetics of buprenorphine, alfentanil, sufentanil and remifentanil change little in patients with renal failure, the continuous administration of fentanyl can lead to prolonged sedation.
肾功能不全患者通常需要使用阿片类镇痛药以提供充分的疼痛缓解。由于代谢产物可能蓄积,肾功能不全患者使用吗啡、哌替啶(度冷丁)和右丙氧芬的情况较为复杂。虽然吗啡本身在很大程度上不受肾衰竭影响,但已有报道称,活性代谢产物(吗啡-6-葡萄糖醛酸苷)和主要代谢产物(吗啡-3-葡萄糖醛酸苷,被认为具有阿片拮抗剂特性)均出现蓄积,表现为平均峰浓度和浓度-时间曲线下面积增加。分别给予肾功能不全患者哌替啶和右丙氧芬后,毒性代谢产物去甲哌替啶和去甲丙氧芬的消除半衰期延长,因此常规使用这些药物并不明智。有肾功能不全患者使用可待因和二氢可待因后出现长时间麻醉的病例报告,提示在这种情况下开具这些药物时需谨慎。虽然肾衰竭患者中丁丙诺啡、阿芬太尼、舒芬太尼和瑞芬太尼的药代动力学变化不大,但持续给予芬太尼可导致镇静时间延长。