Sogorb-Sánchez M A, Vilanova-Gisbert E, Carrera-González V
Unidad de Toxicología y Seguridad Química, Instituto de Bioingeniería, Universidad Miguel Hernández, Elche, Alicante, Spain.
Rev Neurol. 2004;39(8):739-47.
Organophosphorus compounds are worldwide employed as insecticides and are yearly responsible of several millions of poisonings. The chemical structure of most of the warfare nerve agents also corresponds with an organophosphorus compound. Organophosphorus insecticides and warfare nerve agents exert their main toxicological effects through inhibition of acetylcholinesterase. Current treatments of patients poisoned with organophosphorus compounds include atropine (in order to protect muscarinic receptors), oximes (in order to accelerate the reactivation of the inhibited acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). The administration of phosphotriesterases (enzymes involved in the detoxication of organophosphorus compounds through hydrolysis) is a very effective treatment against poisonings by organophosphorus insecticides and warfare nerve agents. There are experimental preventive treatments based on the simultaneous administration of carbamates and certain antimuscarinic drugs, different from atropine, which notably improve the efficacy of the classical treatments applied after poisonings by warfare nerve agents.
The treatments based in the administration of phosphotriesterases might be the response to the call of the World Health Organization for searching new treatments with capability to reduce the high mortality recorded in the cases of poisonings by organophosphorus compounds. These treatments can be applied in a preventive way without the intrinsic neurotoxicity associated to the preventive treatments based on carbamates and antimuscarinic drugs. Therefore, these treatments are specially interesting for people susceptible to suffer severe exposures, i.e. sprayers in the farms.
有机磷化合物在全球范围内被用作杀虫剂，每年导致数百万起中毒事件。大多数战争神经毒剂的化学结构也与有机磷化合物相对应。有机磷杀虫剂和战争神经毒剂主要通过抑制乙酰胆碱酯酶发挥其毒理学作用。目前对有机磷化合物中毒患者的治疗包括使用阿托品（以保护毒蕈碱受体）、肟类药物（以加速被抑制的乙酰胆碱酯酶的重新激活）和苯二氮䓬类药物（以避免惊厥）。给予磷酸三酯酶（通过水解参与有机磷化合物解毒的酶）是治疗有机磷杀虫剂和战争神经毒剂中毒的一种非常有效的方法。有基于同时给予氨基甲酸盐和某些不同于阿托品的抗毒蕈碱药物的实验性预防治疗方法，这显著提高了战争神经毒剂中毒后应用的传统治疗方法的疗效。
基于给予磷酸三酯酶的治疗方法可能是对世界卫生组织呼吁寻找能够降低有机磷化合物中毒病例中高死亡率的新治疗方法的回应。这些治疗方法可以以预防的方式应用，而不会产生与基于氨基甲酸盐和抗毒蕈碱药物的预防治疗相关的内在神经毒性。因此，这些治疗方法对易遭受严重暴露的人群，即农场中的喷雾器操作员特别有意义。
