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Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment.
Advances in clinical chemistry. Pub Date : 2004
Bajgar, Jiri

OP/nerve agents are still considered as important chemicals acting on living organisms and are widely used. They are characterized according to their action as compounds influencing cholinergic nerve transmission via inhibition of AChE. Modeling of this action and extrapolation of experimental data from animals to humans is more possible for highly toxic agents than for the OP. 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 molecular forms. The activity of both enzymes (and molecular forms) is influenced by inhibitors (reversible, irreversible, and allosteric) 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 subsequent detection of free SH-group of the released thiocholine. The diagnosis of OP/nerve agent poisoning is based on anamnesis, the clinical status of the intoxicated organism, and on cholinesterase determination in the blood. For nerve agent intoxication, AChE in the red blood cell is more diagnostically important than BuChE activity in the plasma. This enzyme is a good diagnostic marker for intoxication with OP pesticides. Some other biochemical examinations are recommended, especially arterial blood gas, blood pH, minerals, and some other specialized parameters usually not available in all clinical laboratories. These special examinations are important for prognosis of the intoxication, for effective treatment, and for retrospective analysis of the agent used for exposure. Some principles of prophylaxis against OP/nerve agent 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 agent OP poisoning are described. They are based on the administration of anticholinergics (mostly atropine but some other anticholinergics can be recommended) as a symptomatic treatment, cholinesterase reactivators as a causal treatment (different types but without a universal reactivator against all OP/nerve agents) as the first aid and medical treatment, and anticonvulsants, preferably diazepam though some other effective benzodiazepines are available. New drugs for the treatment are under experimental study based on new approaches to the mechanism of action. Future trends in the complex research of these compounds, which is important not only for the treatment of intoxication but also for the quantitative and qualitative increase of our knowledge of toxicology, neurochemistry, neuropharmacology, clinical biochemistry, and analytical chemistry in general, are characterized.

中文翻译:

有机磷酸盐/神经毒剂中毒:作用机理,诊断,预防和治疗。

OP /神经毒剂仍被认为是作用于活生物体的重要化学物质,并被广泛使用。它们根据其作用被表征为通过抑制AChE影响胆碱能神经传递的化合物。与OP相比,高毒性药物更可能对此行为进行建模并从动物向人类推断实验数据。中毒症状包括烟碱,毒蕈碱和中枢症状。对于某些OP /神经制剂,观察到延迟的神经毒性。胆碱酯酶(AChE和BuChE)的特征是参与这些化合物(包括分子形式)毒性作用的主要酶。两种酶(和分子形式)的活性均受抑制剂(可逆,不可逆和变构)和其他因素(例如病理状态)的影响。胆碱酯酶的测定方法不同。但是,最常见的方法是基于硫代胆碱酯的水解并随后检测释放的硫代胆碱的游离SH-基团的方法。OP /神经毒剂中毒的诊断基于回忆,中毒生物体的临床状况以及血液中胆碱酯酶的测定。对于神经毒剂中毒,红细胞中的AChE比血浆中的BuChE活性更具诊断意义。该酶是OP农药中毒的良好诊断标记。建议进行其他一些生化检查,尤其是动脉血气,血液pH值,矿物质和一些其他专门参数,这些参数通常并非在所有临床实验室中都可用。这些特殊检查对于中毒的预后很重要,进行有效治疗,以及对用于暴露的药剂进行回顾性分析。给出了一些预防OP /神经毒剂中毒的原理,包括可逆性胆碱酯酶抑制剂(如吡啶斯的明(单独或与其他药物组合)的给药),清除剂(如胆碱酯酶的制剂),某些治疗药物以及可能的组合。描述了治疗神经毒剂OP中毒的基本原理。它们基于对症治疗,主要是抗胆碱药(主要是阿托品,但也可以推荐其他一些抗胆碱药),作为因果治疗的胆碱酯酶激活剂(不同类型,但没有针对所有OP /神经药的通用激活剂)作为急救药物,医疗和抗惊厥药,尽管可获得一些其他有效的苯二氮卓类药物,但优选地西epa。正在根据作用机理的新方法对用于治疗的新药物进行实验研究。表征了这些化合物的复杂研究的未来趋势,这不仅对中毒的治疗很重要,而且对于我们毒理学,神经化学,神经药理学,临床生物化学和分析化学的知识的定量和定性提高也具有重要意义。
更新日期:2017-01-31
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