A review of the potential role of methylnaltrexone in opioid bowel dysfunction
A review of the potential role of methylnaltrexone in opioid bowel dysfunction
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DOI：
10.1016/s0002-9610(01)00783-8
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发表时间：
2001-11-01
影响因子：
3
通讯作者：
Foss, JF
中科院分区：
文献类型：
--
作者：
Foss, JF
阿片类药物是晚期癌症患者广泛使用的止痛药。然而，它们的止痛效果往往受到最常见的副作用-阿片类肠道功能障碍(OBD)的限制。由于传统的松弛疗法在治疗OBD方面往往无效，因此需要研究替代方法。阿片类药物对肠道的作用似乎主要是通过胃肠道(GI)的受体而不是中枢神经系统(CNS)的受体介导的，阿片类拮抗剂，如纳洛酮、纳曲酮和纳美芬，已被研究为对抗阿片类药物的外周效应，但这些药物可以进入中枢并逆转镇痛或引起阿片类药物戒断症状。甲基纳曲酮(MNTX)是一种新型的纳曲酮的四元衍生物，不会通过血脑屏障，是一种选择性的外周阿片受体拮抗剂。在正常志愿者中，静脉或口服MNTX可逆转阿片类药物引起的肠动力下降，而不影响止痛。口服后MNTX的生物利用度较低，其血药浓度与其在肠道中的作用无相关性，提示MNTX主要是局部作用于肠道。在接受长期阿片类药物治疗的患者中，静脉或口服MNTX在所有受试者中都有效地减少了口-盲肠转运的延迟，并在没有引起戒断症状的情况下引发了松弛反应。MNTX是一种外周选择性阿片类拮抗剂，可能在治疗OBD方面具有临床实用价值，副作用最小。(C)2001 Excerpta Medica，Inc.保留所有权利。
Opioids are widely used analgesics in patients with advanced cancer. However, their effectiveness for pain relief is often limited by the most frequently Occurring side effect, opioid bowel dysfunction (OBD). Because conventional laxation measures are often ineffective in treating OBD, alternative approaches need to be investigated. Opioid action on the gut appears to be mediated mainly by receptors in the gastrointestinal (GI) tract rather than by those in the central nervous system (CNS), Opioid antagonists, such as naloxone, naltrexone, and nalmefene, have been studied as a means of antagonizing the peripheral effects of opioids, but these agents can enter the CNS and reverse analgesia or cause opioid withdrawal symptoms. Methylnaltrexone (MNTX) is a novel quaternary derivative of naltrexone that does not cross the blood-brain barrier and acts as a selective peripheral opioid receptor antagonist. In normal volunteers, intravenous or oral MNTX reverses opioid-induced reduction in bowel motility without affecting analgesia. Bioavailability of MNTX is low after oral administration., and plasma levels do not correlate with its actions in the gut, suggesting a predominantly local luminal action of MNTX on the gut. In patients receiving long-term opioid therapy, MNTX administered intravenously or orally was effective in reducing the delay in oral-cecal transit and eliciting laxation responses in all subjects without causing withdrawal symptoms. MNTX is a peripherally selective opioid antagonist that may have clinical utility in managing OBD with minimal adverse effects. (C) 2001 Excerpta Medica, Inc. All rights reserved.