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对神经毒剂和有机磷中毒的复杂观点。

Complex view on poisoning with nerve agents and organophosphates.

作者信息

Bajgar Jirí

机构信息

University of Defence, Faculty of Military Health Sciences, Department of Toxicology, Hradec Kralové, Czech Republic.

出版信息

Acta Medica (Hradec Kralove). 2005;48(1):3-21.

Abstract

OP/nerve agents are still considered as important chemicals acting on living organisms and widely used in human practice. Nerve agents are the most lethal chemical warfare agents. They are characterized according to their action as compounds influencing cholinergic nerve transmission via inhibition of AChE. The symptoms of intoxication comprise nicotinic, muscarinic and central symptoms, for some OP/nerve agents, a delayed neurotoxicity is observed. Cholinesterases (AChE and BuChE) are characterized as the main enzymes involved in the toxic effect of these compounds including their molecular forms. The activity of both enzymes (and molecular forms) is influenced by inhibitors and other factors such as pathological states. There are different methods for cholinesterase determination, however, the most frequent is the method based on the hydrolysis of thiocholine esters and following detection of free SH-group of the released thiocholine. The diagnosis of OP/nerve agents poisoning is based on anamnesis, the clinical status of the intoxicated organism and on cholinesterase determination in the blood. Some principles of prophylaxis against OP/nerve agents poisoning comprising the administration of reversible cholinesterase inhibitors such as pyridostigmine (alone or in combination with other drugs), scavengers such as preparations of cholinesterases, some therapeutic drugs and possible combinations are given. Basic principles of the treatment of nerve agents/OP poisoning are described. New drugs for the treatment are under experimental study based on new approaches to the mechanism of action.

摘要

有机磷/神经毒剂仍被视为作用于生物体的重要化学物质,并在人类实践中广泛使用。神经毒剂是最致命的化学战剂。根据其作用,它们被归类为通过抑制乙酰胆碱酯酶影响胆碱能神经传递的化合物。中毒症状包括烟碱样、毒蕈碱样和中枢症状,对于某些有机磷/神经毒剂,还会观察到迟发性神经毒性。胆碱酯酶(乙酰胆碱酯酶和丁酰胆碱酯酶)是参与这些化合物毒性作用的主要酶,包括它们的分子形式。这两种酶(及其分子形式)的活性受抑制剂和其他因素(如病理状态)的影响。有不同的胆碱酯酶测定方法,然而,最常用的是基于硫代胆碱酯水解并随后检测释放的硫代胆碱游离巯基的方法。有机磷/神经毒剂中毒的诊断基于病史、中毒生物体的临床状况以及血液中胆碱酯酶的测定。给出了一些预防有机磷/神经毒剂中毒的原则,包括给予可逆性胆碱酯酶抑制剂(如吡啶斯的明,单独或与其他药物联合使用)、清除剂(如胆碱酯酶制剂)、一些治疗药物以及可能的组合。描述了神经毒剂/有机磷中毒的基本治疗原则。基于新的作用机制方法,正在对治疗新药进行实验研究。

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