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药物遗传学:对抗阿片类药物流行的精准医学方法。

Pharmacogenetics: A Precision Medicine Approach to Combatting the Opioid Epidemic.

作者信息

Smith D Max, Stevenson James M, Ho Teresa T, Formea Christine M, Gammal Roseann S, Cavallari Larisa H

机构信息

MedStar Health, Columbia, Maryland, USA.

Department of Oncology, Georgetown University Medical Center, Washington, DC, USA.

出版信息

J Am Coll Clin Pharm. 2022 Feb;5(2):239-250. doi: 10.1002/jac5.1582. Epub 2021 Dec 19.

Abstract

Ineffective pain control is the most commonly cited reason for misuse of prescription opioids and is influenced by genetics. In particular, the gene encoding the CYP2D6 enzyme, which metabolizes some of the most commonly prescribed opioids (e.g., tramadol, hydrocodone) to their more potent forms, is highly polymorphic and can lead to reduced concentrations of the active metabolites and decreased opioid effectiveness. Consideration of the genotype may allow for predicting opioid response and identifying patients who are likely to respond well to lower potency opioids as well as those who may derive greater pain relief from non-opioid analgesics versus certain opioids. There is emerging evidence that a -guided approach to pain management improves pain control and reduces opioid consumption and thus may be a promising means for combating opioid misuse. Clinical practice guidelines are available for select opioids and other analgesics to support medication and dose selection based on pharmacogenetic data. This article describes the evidence supporting genotype-guided pain management as a means of improving pain control and reducing opioid misuse and clinical recommendations for genotype-guided analgesic prescribing. In addition, a "how to" guide using patient case examples is provided to demystify the process for implementing pharmacogenetics-guided pain management in order to optimize analgesia and minimize adverse effects. Optimizing pain management through genotype-guided approaches may ultimately provide safer and more effective therapy for pain control while decreasing the risk for opioid misuse.

摘要

疼痛控制不佳是处方阿片类药物滥用最常被提及的原因,且受基因影响。特别是,编码CYP2D6酶的基因具有高度多态性,该酶可将一些最常用的阿片类药物(如曲马多、氢可酮)代谢为更强效的形式,这可能导致活性代谢物浓度降低以及阿片类药物疗效下降。考虑基因型可能有助于预测阿片类药物反应,并识别出可能对低效阿片类药物反应良好的患者,以及那些与某些阿片类药物相比可能从非阿片类镇痛药中获得更大疼痛缓解的患者。越来越多的证据表明,以基因为导向的疼痛管理方法可改善疼痛控制并减少阿片类药物的使用,因此可能是对抗阿片类药物滥用的一种有前景的手段。针对特定阿片类药物和其他镇痛药有临床实践指南,以支持基于药物遗传学数据的药物和剂量选择。本文描述了支持以基因为导向的疼痛管理作为改善疼痛控制和减少阿片类药物滥用手段的证据,以及关于以基因为导向的镇痛药处方的临床建议。此外,还提供了一个使用患者案例的“操作指南”,以揭开实施药物遗传学导向的疼痛管理过程的神秘面纱,从而优化镇痛效果并将不良反应降至最低。通过以基因为导向的方法优化疼痛管理,最终可能为疼痛控制提供更安全、更有效的治疗,同时降低阿片类药物滥用的风险。

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