Strachan E M, Kelly C A, Bateman D N
Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, 51 Little France Crescent, EH16 4SA, Edinburgh, Scotland, UK.
Eur J Clin Pharmacol. 2004 Oct;60(8):541-5. doi: 10.1007/s00228-004-0811-7. Epub 2004 Sep 15.
To examine the effects of anti-psychotic medications on cardiovascular parameters in overdose. Specifically, to examine dose-response relationships for thioridazine and chlorpromazine.
A retrospective study of case records of patients presenting to the Edinburgh poisons treatment unit over 3 years (2000-2002). Information--including that on stated dose ingested, ECG parameters, and pulse and blood pressure--was extracted from case notes.
A total of 224 chlorpromazine, 96 thioridazine and 99 patients ingesting other anti-psychotics were evaluated. Full data on all aspects, both dose and cardiovascular change, was available in 96 chlorpromazine, 36 thioridazine and 27 of the other anti-psychotic cases. For thioridazine, there was a significant dose-response relationship for increasing heart rate and increasing QTc but not other cardiovascular changes. For chlorpromazine, there was no dose-response relationship for ECG changes, but there was a significant dose-response relationship for increasing heart rate and reduction in mean blood pressure.
We have confirmed a relationship between increasing dose of thioridazine and prolongation of QTc in overdose patients. No such change was observed with chlorpromazine. Both of these agents are reported to cause QT prolongation, but this study suggests that the nature of these effects is different for each agent. Poisoned patients may offer ways of exploring in more detail, and at a larger dose range, the effects of potentially cardiotoxic drugs in humans.
研究抗精神病药物过量服用时对心血管参数的影响。具体而言,研究硫利达嗪和氯丙嗪的剂量 - 反应关系。
对爱丁堡中毒治疗中心3年(2000 - 2002年)期间患者的病例记录进行回顾性研究。从病例记录中提取信息,包括所服用药物的规定剂量、心电图参数以及脉搏和血压。
共评估了224例服用氯丙嗪、96例服用硫利达嗪以及99例服用其他抗精神病药物的患者。在96例氯丙嗪、36例硫利达嗪以及27例其他抗精神病药物病例中,可获取关于剂量和心血管变化各方面的完整数据。对于硫利达嗪,心率增加和QTc延长存在显著的剂量 - 反应关系,但其他心血管变化不存在此关系。对于氯丙嗪,心电图变化不存在剂量 - 反应关系,但心率增加和平均血压降低存在显著的剂量 - 反应关系。
我们已证实过量服用患者中硫利达嗪剂量增加与QTc延长之间存在关联。氯丙嗪未观察到此类变化。据报道这两种药物均可导致QT延长,但本研究表明每种药物的此类效应性质不同。中毒患者可能为更详细地探索潜在心脏毒性药物在更大剂量范围内对人体的影响提供途径。