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阿片类药物所致肠道功能障碍治疗模式的演变

Evolving paradigms in the treatment of opioid-induced bowel dysfunction.

作者信息

Poulsen Jakob Lykke, Brock Christina, Olesen Anne Estrup, Nilsson Matias, Drewes Asbjørn Mohr

机构信息

Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

出版信息

Therap Adv Gastroenterol. 2015 Nov;8(6):360-72. doi: 10.1177/1756283X15589526.

Abstract

In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.

摘要

近年来,阿片类药物的处方量显著增加。尽管阿片类药物在疼痛管理方面有效,但相当一部分接受阿片类药物治疗的患者会出现令人烦恼的胃肠道不良反应。这可能导致治疗困难,进而导致疼痛缓解不足。这些不良反应统称为阿片类药物引起的肠功能障碍,是外源性阿片类药物与胃肠道中的阿片受体结合的结果。这会导致三种重要的胃肠功能紊乱:蠕动、括约肌功能协调和分泌。在临床上,这表现为多种症状,如反流、腹胀、腹部绞痛、硬便、干便和排便不尽,尽管最常见的不良反应是阿片类药物引起的便秘。传统的泻药治疗往往不够充分,但近年来已经引入了一些新的药理学方法。在这篇综述中,介绍了阿片类药物引起的肠功能障碍的病理生理学、症状学和患病率,以及阿片类药物引起的便秘的建议共识定义的益处和注意事项。最后,对传统治疗进行了评估,并与最新的药理学进展进行了比较。总之,仅限于外周的阿片类拮抗剂显示出有希望的结果,但使用不同的定义和结局指标使比较变得复杂。然而,一个国际工作组最近提出了阿片类药物引起的便秘的共识定义,并且也提出了相关的结局指标。如果该领域的研究人员采用建议的共识,并纳入与上消化道功能障碍相关的症状,这将便于比较,并在未来研究中向前迈进一步。

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