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阿片类药物引起的便秘和肠道功能障碍的管理:意大利多学科专家组的专家意见。

Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel.

机构信息

Department of Translational Medicine, University of Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy.

School of Specialization in Geriatric Medicine, University of Milan, Milan, Italy.

出版信息

Adv Ther. 2021 Jul;38(7):3589-3621. doi: 10.1007/s12325-021-01766-y. Epub 2021 Jun 4.

Abstract

The prescribing and use of opioid analgesics is increasing in Italy owing to a profusion in the number and types of opioid analgesic products available, and the increasing prevalence of conditions associated with severe pain, the latter being related to population aging. Herein we provide the expert opinion of an Italian multidisciplinary panel on the management of opioid-induced constipation (OIC) and bowel dysfunction. OIC and opioid-induced bowel dysfunction are well-recognised unwanted effects of treatment with opioid analgesics that can profoundly affect quality of life. OIC can be due to additional factors such as reduced mobility, a low-fibre diet, comorbidities, and concomitant medications. Fixed-dose combinations of opioids with mu (μ) opioid receptor antagonists, such as oxycodone/naloxone, have become available, but have limited utility in clinical practice because the individual components cannot be independently titrated, creating a risk of breakthrough pain as the dose is increased. A comprehensive prevention and management strategy for OIC should include interventions that aim to improve fibre and fluid intake, increase mobility or exercise, and restore bowel function without compromising pain control. Recommended first-line pharmacological treatment of OIC is with an osmotic laxative (preferably polyethylene glycol [macrogol]), or a stimulant laxative such as an anthraquinone. A second laxative with a complementary mechanism of action should be added in the event of an inadequate response. Second-line treatment with a peripherally acting μ opioid receptor antagonist (PAMORA), such as methylnaltrexone, naloxegol or naldemedine, should be considered in patients with OIC that has not responded to combination laxative treatment. Prokinetics or intestinal secretagogues, such as lubiprostone, may be appropriate in the third-line setting, but their use in OIC is off-label in Italy, and should therefore be restricted to settings such as specialist centres and clinical trials.

摘要

由于可供选择的阿片类镇痛药的数量和种类繁多,以及与严重疼痛相关的疾病的发病率不断上升(后者与人口老龄化有关),意大利的阿片类镇痛药的开具和使用正在增加。本文提供了一个意大利多学科专家组对阿片类药物引起的便秘(OIC)和肠道功能障碍管理的专家意见。OIC 和阿片类药物引起的肠道功能障碍是阿片类药物治疗的公认的不良作用,可严重影响生活质量。OIC 可能是由于其他因素引起的,如活动减少、低纤维饮食、合并症和同时使用的药物。阿片类药物与 μ 型阿片受体拮抗剂(如羟考酮/纳洛酮)的固定剂量组合已经上市,但在临床实践中的应用有限,因为不能独立调整各个成分的剂量,随着剂量的增加,会有突破性疼痛的风险。OIC 的全面预防和管理策略应包括旨在改善纤维和液体摄入、增加活动或运动以及在不影响疼痛控制的情况下恢复肠道功能的干预措施。OIC 的一线推荐药物治疗是使用渗透性泻药(最好是聚乙二醇[聚乙二醇])或刺激性泻药,如蒽醌。如果反应不足,应添加具有互补作用机制的第二种泻药。对于未对联合泻药治疗有反应的 OIC 患者,应考虑使用外周作用 μ 型阿片受体拮抗剂(PAMORA),如甲基纳曲酮、纳洛酮或纳美芬。在三线治疗中,可能适合使用促动力药或肠道分泌剂,如鲁比前列酮,但在意大利,它们在 OIC 中的使用是超适应证的,因此应仅限于专科中心和临床试验等环境中使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c50/8279968/acaf32f163b9/12325_2021_1766_Fig1_HTML.jpg

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