Non-muscarinic therapeutic targets for acute organophosphorus poisoning.
Non-muscarinic therapeutic targets for acute organophosphorus poisoning.
复制标题
急性有机磷中毒的非毒蕈碱治疗靶点。
DOI：
10.1007/s13181-010-0093-7
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Bird,StevenB
中科院分区：
文献类型：
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作者：
Rosenbaum,Christopher;Bird,StevenB
有机磷（OP）农药是一大类乙酰胆碱酯酶抑制剂，其在全世界造成巨大的发病率和死亡率，估计每年造成300，000人死亡。目前急性OP中毒的药物治疗包括使用阿托品、肟和苯二氮卓类药物。然而，即使采用这种疗法，这些药物的死亡率也高达40%。人们日益认识到，并非所有业务方案都是一样的。它们的毒性、亲脂性和对肟治疗的反应存在显著差异。OP农药还存在其他非毒蕈碱效应，如急性和慢性神经肌肉接头衰竭和中枢呼吸衰竭。部分原因是这些化学物质造成的死亡大多发生在发展中国家，美国国立卫生研究院（NIH）很少针对这些物质进行研究。然而，OP杀虫剂和军用神经毒剂的作用机制相似，沿着对化学恐怖主义的日益关注，导致了NIH化学威胁对策（CounterACT）计划的形成。作为CounterACT计划的一部分，NIH最近将六种OP杀虫剂指定为“威胁剂”。本概念文件描述了与有机磷农药的非毒蕈碱效应有关的一些知识空白，并强调了需要进一步研究的领域。利用目前NIH对这些化学品的兴趣，发展中国家的医疗必需品提供了在日常需要的地方提供新疗法的可能性。
Organophosphorus (OP) pesticides are a broad class of acetylcholinesterase inhibitors that are responsible for tremendous morbidity and mortality worldwide, contributing to an estimated 300,000 deaths annually. Current pharmacotherapy for acute OP poisoning includes the use of atropine, an oxime, and benzodiazepines. However, even with such therapy, the mortality from these agents is as high as 40%. It is increasingly recognized that not all OPs are the same. Significant differences exist in their toxicity, lipophilicity, and response to oxime therapy. Other non-muscarinic effects of OP pesticides exist, such as acute and chronic neuromuscular junction failure and central respiratory failure. In part because most of the mortality from these chemicals takes place in the developing world, little National Institutes of Health (NIH) research has been directed towards these agents. However, the similar mechanism of action of OP pesticides and the military nerve agents, along with increasing concerns about chemical terrorism has lead to the formation of the NIH Countermeasures Against Chemical Threats (CounterACT) Program. As part of the CounterACT Program, the NIH has recently designated six OP pesticides as “threat agents”. This concept paper describes some of the knowledge gaps related to non-muscarinic effects of OP pesticides and highlights needed areas of further research. Leveraging the current NIH interest in these chemicals to medical necessities in the developing world offers the possibility of delivering new therapeutics where they are needed on a daily basis.