有机磷中毒救治药物研究及其临床应用

Drug research and clinical application of organophosphorous poisoning

急性有机磷农药中毒(AOPP)是临床常见的急危重症之一,病死率极高。有机磷杀虫剂通过抑制神经接头处的乙酰胆碱酯酶(AChE)活性,使乙酰胆碱(ACh)蓄积,引起先兴奋后抑制的胆碱能症状。中毒早期应联合应用抗胆碱能药物及AChE复能剂。阿托品和盐酸戊乙奎醚(长托宁)是最常用的抗胆碱能药物,能有效争夺ACh受体,对AOPP所致的胆碱能危象起到治"标"的作用;肟类化合物能够使被抑制的AChE恢复其水解ACh的活性。此外,脂肪乳、新型解毒药物、血液净化和中药辅助治疗AOPP也越来越受到关注。目前,对AOPP药物研究及中毒救治认识已经取得相当大的进展,结合药理学和毒理学等相关领域最新研究将对AOPP救治产生重要影响。

Acute organophosphorus pesticides poisoning（AOPP）is one of the common critical emergency problems and the fatality is extremely high. Organophosphorus pesticides（OPS）are highly effective acetylcholinesterase（AChE）inhibitors. The AChE inhibition results in accumulation of acetylcholine and overestimation of acetylcholine receptors in synapses of the autonomic nervous system,central nervous system,and neuromuscular junctions,causing a series of symptoms including muscarinic,nicotinic,and central nervous system dysfunctions. In the early stage of AOPP,the core treatment is the use of anticholinergic drugs coupled with cholinesterase reactivator. Atropine and penehyclidine hydrochloride（Tuoning）are the most commonly used anticholinergic drugs,which can effectively compete with acetylcholine receptors,block the effect of acetylcholine,and relieve the symptoms of respiratory failure,bronchospasm,pulmonary edema caused by AOPP. Oximes are believed to function as AChE reactivators,that can promote enzymatic reactivation and restore the activity of hydrolysis of acetylcholine. Recently,new avproaches,such as intravenous lipid emulsion,new detoxification drugs,blood purification,and traditional Chinese medicine,have attracted more attention. Overall,great progress has been made in AOPP treatments. A better understanding of AOPP mechanism,and the support from pharmacology,toxicology,and related fields can contribute to the treatment of AOPP. Improved medical management of AOPP can also result in fewer deaths from poisoning worldwide.