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慢性疼痛和阿片类药物使用障碍患者的长期减药:药物遗传学和性别差异。

Long-term deprescription in chronic pain and opioid use disorder patients: Pharmacogenetic and sex differences.

机构信息

1Neuropharmacology applied to Pain (NED) Alicante Institute for Health and Biomedical Research (ISABIAL), c/Pintor Baeza, 12 03010, Alicante, Spain.

2Institute of Bioengineering, Miguel Hernández University, Avda. de la Universidad s/n, 03202, Elche, Spain.

出版信息

Acta Pharm. 2023 Jun 12;73(2):227-241. doi: 10.2478/acph-2023-0018. Print 2023 Jun 1.

Abstract

More than half of patients with opioid use disorder for chronic non-cancer pain (CNCP) reduced their dose through a progressive opioid withdrawal supported by a rotation to buprenorphine and/or tramadol. The aim of this research is to analyse the long-term effectiveness of opioid deprescription taking into account the impact of sex and pharmacogenetics on the inter-individual variability. A cross-sectional study was carried out from October 2019 to June 2020 on CNCP patients who had previously undergone an opioid deprescription ( = 119 patients). Demographic, clinical (pain, relief and adverse events) and therapeutic (analgesic use) outcomes were collected. Effectiveness (< 50 mg per day of morphine equivalent daily dose without any aberrant opioid use behaviour) and safety (number of side-effects) were analysed in relation to sex differences and pharmacogenetic markers impact [ genotype (rs1799971) and CYP2D6 phenotypes]. Long-term opioid deprescription was achieved in 49 % of the patients with an increase in pain relief and a reduction of adverse events. CYP2D6 poor metabolizers showed the lowest long-term opioid doses. Here, women showed a higher degree of opioid deprescription, but increased use of tramadol and neuromodulators, as well as an increased number of adverse events. Long-term deprescription was successful in half of the cases. Understanding sex and gender interaction plus a genetic impact could help to design more individualized strategies for opioid deprescription.

摘要

超过一半的慢性非癌性疼痛(CNCP)伴阿片类药物使用障碍的患者通过支持逐渐减少阿片类药物剂量并转为丁丙诺啡和/或曲马多的方法来减少剂量。本研究旨在分析阿片类药物减用的长期效果,同时考虑到性别和药物遗传学对个体间差异的影响。2019 年 10 月至 2020 年 6 月期间,对先前接受过阿片类药物减用治疗的 CNCP 患者(n=119)进行了一项横断面研究。收集了人口统计学、临床(疼痛、缓解和不良反应)和治疗(镇痛药物使用)结局。分析了有效性(<50mg 等效每日吗啡剂量且无异常阿片类药物使用行为)和安全性(不良反应数量)与性别差异和药物遗传学标志物影响[基因型(rs1799971)和 CYP2D6 表型]之间的关系。49%的患者实现了长期阿片类药物减用,疼痛缓解程度增加,不良反应减少。CYP2D6 弱代谢者的长期阿片类药物剂量最低。在这里,女性表现出更高程度的阿片类药物减用,但增加了曲马多和神经调节剂的使用,以及更多的不良反应。半数患者长期减用成功。了解性别和性别相互作用以及遗传影响可能有助于为阿片类药物减用设计更个体化的策略。

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