Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, 55 Claverick St, Providence, RI, 02903, USA.
Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Ground Silverstein, Rm. 260 3400 Spruce St, Philadelphia, PA, 19104, USA.
J Med Toxicol. 2021 Jan;17(1):10-15. doi: 10.1007/s13181-020-00795-3. Epub 2020 Jul 9.
Buprenorphine is a unique μ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited.
A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures.
Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death.
Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.
丁丙诺啡是一种独特的 μ 阿片受体部分激动剂,具有强烈的受体结合能力、名义上的愉悦奖励作用和镇静及呼吸抑制的封顶效应。尽管药理学特性提高了安全性,但在毒理学研究中仍有丁丙诺啡导致的致命阿片类药物过量的病例报告,但文献中这些病例的细节有限。
使用罗德岛州卫生署州非故意药物过量报告系统(SUDORS)数据库,对 2016 年至 2018 年罗德岛州涉及阿片类药物的药物过量致死病例进行回顾性审查。比较毒理学检测有丁丙诺啡和/或去甲丁丙诺啡的与无丁丙诺啡的阿片类药物过量死亡病例,以评估共同暴露的类型和数量。
在 534 例涉及阿片类药物的死亡中,29 例(5.4%)毒理学检测有丁丙诺啡和/或去甲丁丙诺啡。最常见的共同暴露物如下:芬太尼(75.9%)、去甲芬太尼(72.4%)、可卡因(41.4%)、苯甲酰爱康宁(41.4%)、大麻素(31.0%)、乙醇(31.0%)、左旋咪唑(31.0%)和游离吗啡(31.0%)。有丁丙诺啡的死亡者平均共同暴露物数量为 9.24 种,而无丁丙诺啡的死亡者为 6.68 种。在一个案例中,丁丙诺啡是唯一导致死亡的药物;所有其他毒理学检测有丁丙诺啡的死亡病例均报告了其他导致死亡的药物。
毒理学检测有丁丙诺啡的死者通常有记录的多物质使用。尽管数据有限,但丁丙诺啡可能对包括芬太尼在内的完全激动剂阿片类药物过量有一定的风险缓解作用。进一步的工作应探索丁丙诺啡、去甲丁丙诺啡和其他阿片类代谢物的死后浓度,以确定丁丙诺啡在致命过量药理学中的作用。