在过去的几年中,设计师苯二氮卓类药物(DBZD)越来越多地出现在新型精神活性物质(NPS)市场上。它们通常作为处方苯二氮卓类药物(BZD)的现成替代品出售或添加到假药中。BZDs通常被认为是相对安全的药物,因为在单药中毒中发生严重急性不良反应的风险较低,虽然例如,阿普唑仑似乎显示出呼吸抑制的风险升高。在这里,我们报告了涉及新型DBZD氟拉唑仑的致命中毒。
进行了完整的尸检。通过免疫测定对死后样本进行一般未知的筛查和滥用药物的分析,气相色谱-质谱和液相色谱-质谱。采用标准添加方法对死后血液和组织中的氟哌唑仑进行定量。最后,进行毒理学显著性评分(TSS).
在心脏血清(25.4ng/mL)和外周血(21.9ng/mL)以及尿液中检测到氟帕唑仑,胃内容物,大脑,肝脏和肾脏(65.2-323ng/g)。死亡原因被认为是中枢神经系统(CNS)和呼吸抑制与胃内容物的持续性吸入,在多种药物摄入的背景下。考虑到共同消耗的中枢神经系统抑制剂的浓度水平,氟帕唑仑对死亡的贡献被认为是可能的(TSS为3).
我们的研究结果支持高效力的DBZD如氟拉普唑仑具有增加的非预期毒性风险,特别是与其他中枢神经系统抑制剂有关。对死亡人数进行多学科评估仍然是强制性的,特别是当缺乏有关有毒化合物的药理/毒理学数据时。据我们所知,这是人类固体组织中氟拉唑仑浓度的第一份报告。
Designer benzodiazepines (DBZDs) increasingly emerged on the novel psychoactive substance (NPS) market in the last few years. They are usually sold as readily available alternatives to prescription benzodiazepines (BZDs) or added to counterfeit medicines. BZDs are generally considered relatively safe drugs due to the low risk of serious acute adverse effects in mono-intoxication, though e.g., alprazolam seems to display an elevated risk of respiratory depression. Here we report on a fatal intoxication involving the novel DBZD flualprazolam.
A complete postmortem examination was performed. General unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassay, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. The standard addition method was employed to quantify flualprazolam in postmortem blood and tissues. Finally, a toxicological significance score (TSS) was assigned.
Flualprazolam was detected in heart serum (25.4 ng/mL) and peripheral blood (21.9 ng/mL) as well as in urine, stomach contents, brain, liver and kidney (65.2-323 ng/g). The cause of death was deemed as central nervous system (CNS) and respiratory depression with agonal aspiration of stomach contents, in the setting of a multiple drug intake. Given the concentration levels of the co-consumed CNS depressants, the contribution of flualprazolam to the death was considered likely (TSS of 3).
Our results support that highly potent DBZDs like flualprazolam carry an elevated risk for unintended toxicity, especially in association with other CNS depressants. A multidisciplinary evaluation of fatalities remains mandatory, especially when pharmacological/toxicological data on intoxicating compounds are lacking. To our knowledge this is the first report of flualprazolam concentrations in solid tissues in human.