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羟考酮的超强成瘾潜力:是否到了需要暂停使用的时候了?

Oxycodone's Unparalleled Addictive Potential: Is it Time for a Moratorium?

机构信息

Northern Anesthesia and Pain Medicine, LLC, 10928 Eagle River Rd. #240, Eagle River, AK, 99577, USA.

Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

出版信息

Curr Pain Headache Rep. 2019 Feb 28;23(2):15. doi: 10.1007/s11916-019-0751-7.

DOI:10.1007/s11916-019-0751-7
PMID:30820686
Abstract

PURPOSE OF REVIEW

This study and literature review were carried out to investigate whether oxycodone is the most addictive prescription opioid.

RECENT FINDINGS

This was a cross-sectional survey from a pain management practice in south-central Alaska and review of the literature involving 86 patients diagnosed with opioid dependence/opioid use disorder from 2013 to 2018. Patients were given a list of prescription opioids and asked to identify the one (1) most desirable to themselves, (2) most desirable among drug-using associates or community, and (3) they deemed most addictive. Patients with a history of heroin use were asked which, if any, served as their gateway drug to heroin. The literature was reviewed using a PubMed search for articles containing the words "oxycodone" and "abuse," "addiction," "dependence," "disorder," and "euphoria." Oxycodone was ranked most highly in all four questions (n = 50, 60.2%; n = 46, 75.4%; n = 38, 60.2%; n = 14, 77.8%, respectively) by a wide margin. Numerous observational studies performed over the past few decades have demonstrated the supreme "likability" and abuse and dependence liability/addictiveness of oxycodone, with more recent mechanistic studies illuminating biological underpinnings including markedly increased active transport across the blood-brain barrier, increased phasic dopaminergism in the ventral tegmental area, nucleus accumbens and related striatal reward centers, and possibly increased kappa opioid receptor-mediated withdrawal dysphoria. Oxycodone possesses pharmacologic qualities that render it disproportionately liable to abuse and addiction and the risks of any long-term prescription outweigh the benefits.

摘要

目的综述

本研究和文献复习旨在探讨羟考酮是否是最容易成瘾的处方类阿片类药物。

最近的发现

这是一项横断面调查,来自阿拉斯加中南部的一个疼痛管理实践,同时回顾了 2013 年至 2018 年间涉及 86 例诊断为阿片类药物依赖/阿片类药物使用障碍患者的文献。患者获得一份处方类阿片药物清单,并要求他们指出(1)对自己最理想的一种;(2)在药物使用者或社区中最理想的一种;(3)他们认为最容易成瘾的一种。有海洛因使用史的患者被问及哪种(如果有)是他们使用海洛因的“入门药物”。文献综述使用 PubMed 进行搜索,检索包含“羟考酮”和“滥用”、“成瘾”、“依赖”、“障碍”和“欣快”等词的文章。羟考酮在所有四个问题中排名都最高(n=50,60.2%;n=46,75.4%;n=38,60.2%;n=14,77.8%),且遥遥领先。过去几十年进行的大量观察性研究表明羟考酮具有极高的“可接受性”以及滥用和依赖的倾向/成瘾性,最近的机制研究阐明了其生物学基础,包括明显增加血脑屏障的主动转运、腹侧被盖区、伏隔核和相关纹状体奖赏中心的相位多巴胺能增加,以及可能增加κ阿片受体介导的戒断性痛苦。羟考酮具有使其易滥用和成瘾的药理特性,任何长期处方的风险都超过了益处。

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本文引用的文献

1
A Keynesian (demand reduction) approach to the opioid epidemic.一种针对阿片类药物流行的凯恩斯主义(需求减少)方法。
Pain Manag. 2018 May 1;8(3):155-156. doi: 10.2217/pmt-2018-0003. Epub 2018 May 3.
2
The opioid epidemic: a central role for the blood brain barrier in opioid analgesia and abuse.阿片类药物流行:血脑屏障在阿片类药物镇痛和滥用中起核心作用。
Fluids Barriers CNS. 2017 Nov 29;14(1):32. doi: 10.1186/s12987-017-0080-3.
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Revisiting Oxycodone Analgesia: A Review and Hypothesis.重新审视羟考酮镇痛作用:综述与假说
A Prospective Cohort Study to Determine Which Opioid-Naïve Emergency Department Patients Are at Risk of Persistent Opioid Use.
一项前瞻性队列研究,以确定哪些初次使用阿片类药物的急诊科患者有持续使用阿片类药物的风险。
Ann Emerg Med. 2025 Aug;86(2):179-186. doi: 10.1016/j.annemergmed.2025.02.025. Epub 2025 Apr 5.
4
Identification of Plasma Metabolites Responding to Oxycodone Exposure in Rats.鉴定大鼠体内对羟考酮暴露产生反应的血浆代谢物。
Metabolites. 2025 Feb 4;15(2):95. doi: 10.3390/metabo15020095.
5
Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.作为脑内羟考酮代谢物(吗啡酮)水平及行为潜在候选数量性状基因的Zhx2的验证研究和多组学分析
bioRxiv. 2024 Sep 1:2024.08.30.610534. doi: 10.1101/2024.08.30.610534.
6
Trends in oxycodone and oxycodone-containing analgesics administration for back pain in emergency departments in the USA (2007-2018).美国急诊科治疗背痛的羟考酮及含羟考酮镇痛剂的使用趋势(2007 - 2018年)
World J Emerg Med. 2024;15(3):169-174. doi: 10.5847/wjem.j.1920-8642.2024.002.
7
The influence of drug class on reward in substance use disorders.药物种类对物质使用障碍中奖励的影响。
Pharmacol Biochem Behav. 2024 Jul;240:173771. doi: 10.1016/j.pbb.2024.173771. Epub 2024 Apr 24.
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State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.2000 年至 2021 年美国阿科斯和疾病预防控制中心 Wonder 数据中羟考酮和阿片类药物相关死亡的州级分布差异:一项生态学研究。
BMJ Open. 2024 Mar 7;14(3):e073765. doi: 10.1136/bmjopen-2023-073765.
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Oxycodone, an opioid like the others?羟考酮,与其他阿片类药物类似吗?
Front Psychiatry. 2023 Dec 13;14:1229439. doi: 10.3389/fpsyt.2023.1229439. eCollection 2023.
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Prescription of oxycodone versus codeine after childbirth and risk of persistent opioid use: a population-based cohort study.产后羟考酮与可待因处方与持续性阿片类药物使用风险:基于人群的队列研究。
CMAJ. 2023 Jul 31;195(29):E973-E983. doi: 10.1503/cmaj.221351.
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Trends in the Nonmedical Use of OxyContin, United States, 2006 to 2013.2006年至2013年美国羟考酮非医疗用途趋势
Clin J Pain. 2017 May;33(5):452-461. doi: 10.1097/AJP.0000000000000426.
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CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016.美国 2016 年慢性疼痛阿片类药物处方指南。
MMWR Recomm Rep. 2016 Mar 18;65(1):1-49. doi: 10.15585/mmwr.rr6501e1.
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Self-reports of prescription opioid abuse and diversion among recreational opioid users in a Canadian and a United States city.加拿大和美国一个城市娱乐性阿片类药物使用者中处方阿片类药物滥用和转移的自我报告。
J Opioid Manag. 2015 Nov-Dec;11(6):463-73. doi: 10.5055/jom.2015.0299.
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Trends in opioid analgesic abuse and mortality in the United States.美国阿片类镇痛药滥用和死亡率的趋势。
N Engl J Med. 2015 Jan 15;372(3):241-8. doi: 10.1056/NEJMsa1406143.
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Kentucky seeks $1bn from Purdue Pharma for misrepresenting addictive potential of oxycodone.肯塔基州因普渡制药公司对羟考酮成瘾性的不实陈述而寻求从该公司获得10亿美元赔偿。
BMJ. 2014 Nov 6;349:g6605. doi: 10.1136/bmj.g6605.
10
Tapentadol abuse potential: a postmarketing evaluation using a sample of individuals evaluated for substance abuse treatment.曲马多的滥用可能性:一项使用接受药物滥用治疗评估的个体样本进行的上市后评估。
Pain Med. 2015 Jan;16(1):119-30. doi: 10.1111/pme.12524. Epub 2014 Sep 22.