Becker Gerhild, Galandi Daniel, Blum Hubert E
Department of Internal Medicine II, University Hospital of Freiburg, Freiburg, Germany.
J Pain Symptom Manage. 2007 Nov;34(5):547-65. doi: 10.1016/j.jpainsymman.2006.12.018. Epub 2007 Sep 27.
Many patients treated with opioids suffer from constipation. Opiate- or opioid-related constipation is not only a frequent but also a distressing symptom and difficult to treat. There is emerging evidence regarding a novel approach to the management of opiate-related constipation. The aim of this paper is to collect, critically appraise, and summarize the evidence on the effectiveness of recently developed peripherally acting micro-receptor antagonists in the treatment of opiate-related constipation. A comprehensive search of 11 computerized databases was conducted and efforts were made to identify unpublished and ongoing research. Twenty studies were identified; 13 were randomized controlled trials (RCTs) and 7 were Phase II studies assessing toxicity. Studies were mainly executed in healthy volunteers or members of methadone programs with opioid-induced constipation as a model to mimic the condition of patients on opioids. Two RCTs were conducted in hospice patients. Quality of study design and validity of the findings was assessed in all studies. Data show proof of concept but do not allow a definitive answer concerning the effectiveness of the peripherally acting micro-opioid antagonists methylnaltrexone and alvimopan in managing opiate-related constipation. Further research is needed. If future Phase III trials provide supportive data, opioid antagonists may become a standard therapeutic option for the treatment of opiate-related constipation in patients with advanced cancer.
许多接受阿片类药物治疗的患者会出现便秘。阿片类药物相关便秘不仅常见，而且令人痛苦，难以治疗。关于一种治疗阿片类药物相关便秘的新方法，已有越来越多的证据。本文旨在收集、批判性评价和总结有关最近开发的外周作用微受体拮抗剂治疗阿片类药物相关便秘有效性的证据。对11个计算机化数据库进行了全面检索，并努力识别未发表和正在进行的研究。共识别出20项研究；13项为随机对照试验（RCT），7项为评估毒性的II期研究。研究主要在健康志愿者或美沙酮项目参与者中进行，以阿片类药物引起的便秘作为模型来模拟阿片类药物使用者的情况。两项RCT在临终关怀患者中进行。对所有研究的研究设计质量和研究结果的有效性进行了评估。数据证明了概念，但对于外周作用微阿片类拮抗剂甲基纳曲酮和阿维莫潘治疗阿片类药物相关便秘的有效性，无法给出明确答案。还需要进一步研究。如果未来的III期试验提供支持性数据，阿片类拮抗剂可能会成为晚期癌症患者阿片类药物相关便秘治疗的标准治疗选择。
