Kress Hans G
Department of Special Anaesthesia and Pain Therapy, Medical University of Vienna, Vienna, Austria.
Eur J Pain. 2009 Mar;13(3):219-30. doi: 10.1016/j.ejpain.2008.04.011. Epub 2008 Jun 24.
Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous concerns, however, no analgesic ceiling effect and no antagonism of combined pure mu-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full mu-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an antihyperalgesic effect, which is due -- at least in part -- to antagonistic activity at kappa-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses. Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for up to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis.
多年来，丁丙诺啡在临床实践中并未得到广泛应用，主要是由于基于对动物数据的错误解读而产生的镇痛效力和临床安全性担忧。然而，与之前的担忧相反，在治疗剂量范围内未观察到镇痛封顶效应，也未发现其对联合使用的纯μ-阿片受体激动剂有拮抗作用。在最近的研究中，丁丙诺啡可有效且安全地与全μ-激动剂联合使用，并且基于等效镇痛剂量，在丁丙诺啡和另一种阿片类药物之间切换可提供相当的疼痛缓解效果。此外，丁丙诺啡具有抗痛觉过敏作用，这至少部分归因于其对κ-阿片受体的拮抗活性。丁丙诺啡的药代动力学不受高龄或肾功能不全的影响。此外，与包括吗啡、氢吗啡酮、美沙酮和芬太尼在内的其他阿片类药物相比，丁丙诺啡引起呼吸抑制的风险更低。与吗啡和芬太尼不同，丁丙诺啡在治疗性镇痛剂量下没有免疫抑制活性。透皮丁丙诺啡显著改善了该药物的临床应用，可实现长达96小时的持续丁丙诺啡释放。在临床试验中，与安慰剂相比，接受透皮丁丙诺啡治疗的患者疼痛缓解明显更显著，睡眠质量更好，且救援治疗需求减少。大规模上市后研究证实了透皮丁丙诺啡在治疗中度至重度癌症疼痛和非癌症疼痛（包括神经病变综合征）方面的有效性。最后，中枢神经系统不良事件和便秘的发生率相对较低，并且在严重肾功能不全患者中使用时无需调整剂量，这使得丁丙诺啡非常适合用于糖尿病患者、老年人或肾功能受损个体（包括需要血液透析的患者）等高危患者的慢性疼痛管理。
