Koski A, Vuori E, Ojanperä I
Department of Forensic Medicine, Laboratory of Toxicology, University of Helsinki, Finland.
Hum Exp Toxicol. 2005 Aug;24(8):389-96. doi: 10.1191/0960327105ht542oa.
Drugs and alcohol often occur together in fatal poisonings, complicating the process of determining the cause of death. Especially when found in concentrations generally regarded as toxic but not lethal, the question arises whether the combination of sublethal amounts was the likely cause of death. In this study, we examined poisoning deaths involving amitriptyline, propoxyphene and promazine, which are, after benzodiazepines, the most frequently occurring drugs in Finnish alcohol-related poisonings. From the forensic toxicology database, covering the years 1995-2002, we extracted 332 fatal poisonings, calculated median blood alcohol and drug concentrations, constructed concentration-concentration and concentration-response curves and evaluated the significance of the presence of therapeutic amounts of benzodiazepines. Median amitriptyline and propoxyphene concentrations were lower in alcohol-related cases than in clean drug poisonings. Correspondingly, the median blood alcohol concentrations in all drug-related poisonings were 1.5-2.2 mg/g lower than that found in clean alcohol poisonings. Alcohol concentration proved to be a more sensitive indicator of alcohol-drug interaction than drug concentration. This result suggests that when alcohol is present, relatively small overdoses of the studied drugs may result in fatal poisoning. In this context, fatal drug and alcohol concentrations and the issue of determining the most important agent in fatal drug-alcohol intoxications are discussed.
药物和酒精在致命中毒事件中常常同时出现,这使得确定死因的过程变得复杂。尤其是当发现它们的浓度一般被视为有毒但不致命时,就会出现问题,即亚致死量的药物和酒精共同作用是否可能是死亡原因。在本研究中,我们调查了涉及阿米替林、丙氧芬和异丙嗪的中毒死亡案例,这些药物在芬兰与酒精相关的中毒事件中,是仅次于苯二氮䓬类药物出现频率最高的药物。我们从涵盖1995年至2002年的法医毒理学数据库中提取了332例致命中毒案例,计算了血液中酒精和药物浓度的中位数,构建了浓度-浓度曲线和浓度-反应曲线,并评估了治疗剂量的苯二氮䓬类药物存在的意义。与单纯药物中毒案例相比,与酒精相关案例中的阿米替林和丙氧芬浓度中位数较低。相应地,在所有与药物相关的中毒案例中,血液酒精浓度中位数比单纯酒精中毒案例中的低1.5 - 2.2毫克/克。结果证明,酒精浓度比药物浓度是酒精与药物相互作用更敏感的指标。这一结果表明,当存在酒精时,相对少量的所研究药物过量服用可能导致致命中毒。在此背景下,本文讨论了致命的药物和酒精浓度以及确定致命药物-酒精中毒中最重要因素的问题。