草乌的安全性评价与风险控制措施的探讨

Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix

该文通过全面系统的国内外文献和信息研究,对草乌进行本草溯源及考证、追溯古今文献关于草乌的毒性记载、分析与草乌用药相关的临床不良事件案例报道以及近年来草乌相关的毒性实验研究,从而对草乌及其相关制剂的安全性进行了系统分析,初步总结了与草乌的安全性相关病例的临床特点及潜在风险因素;研究发现,76例草乌临床不良事件病例报道的患者,以心肌损害（占53.9%）、肾损害（占42.1%）为主,提示草乌可能存在心脏毒性和肝肾毒性的安全性问题;草乌成分复杂,研究证明其毒性成分主要取决于双脂型乌头碱的水解或分解程度,实验证明生草乌水煎剂在2 h时毒性最大,约4 h时毒性显著下降。毒性试验研究发现,草乌可能存在心血管系统、神经系统、肾脏、胚胎、生殖毒性等,孕妇应禁用。乌头碱中毒目前还缺乏特效的解毒药,治疗的关键是及时、有效地纠正心律失常,维持生命体征平稳,同时予以洗胃、静脉补液等治疗措施。建议加强草乌毒理相关基础研究,进一步明确其毒性的物质基础、毒性机制和炮制配伍的增效减毒机制,明确量-效关系,充分发挥药物疗效的同时有效消除其安全隐患。

Through the comprehensive and systematic research of domestic and overseas literature and information,we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity,analyzed related adverse cases and the animal toxicity experiments in recent years,then systematically analyzed the safety of Aconitum and its preparations,and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53. 9% and 42. 1% respectively,indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions,and based on the animal experiments,Aconitum decoction had the highest toxicity at 2 h,and it reduced significantly at 4 h,which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study,Aconitum toxicity might occur in cardiovascular system,nervous system,kidney,embryo,reproductive system,and it was contraindicated in pregnant women.So far,specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively,maintain stable vital signs,and meanwhile,give gastric lavage,intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened,and the pharmacology and mechanism of toxicity,as well as the mechanism of processing for raising efficiency and reducing toxicity,should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.