Threat by nerve agents: up-date of diagnostic and therapeutc strategies!
EUSEM eLearning. Thiermann H. Sep 12, 2018; 227602; 38269
Prof. Dr. Horst Thiermann
Prof. Dr. Horst Thiermann
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Nerve agents, either highly volatile or persistent, are strong inhibitors of the acetylcholinesterase.

Self-protection as well as protection of medical facilities is the prerequisite for sufficient therapy.

The clinical diagnosis should be substantiated determination of the decreased activity of acetylcholinesterase.

Atropine, an oxime, at best obidoxime, should be administered as early as possible.
Threat by nerve agents: Update of diagnostic and therapeutic strategies!

H. Thiermann and F. Worek

Bundeswehr Institute of Pharmacology and Toxicology,
80937 Munich, Germany

During the last years, the threat of poisoning by nerve agents shifted into public interest. In Syria civilian population was exposed to Sarin, in Malaysia most probably VX was used for assassination of Kim Jong nam and OPCW confirmed poisoning of Sergej and Yulia Skripal in Salisbury with a nerve agent. Hence an up-date of diagnostic and therapeutic strategies appears rational.
Nerve agents belong to a group of highly toxic chemicals which may be volatile, e.g. Sarin or persistent, e.g. VX. In dependence of the route of exposure, signs and symptoms develop fast after inhalation (Sarin) or with a delay of minutes to few hours after percutaneous resorption (VX). The clinical diagnosis of cholinergic crises can be confirmed on the spot by determination of the decreased activity of acetylcholinesterase. While being protected with appropriate suites and a mask, decontamination and first treatment with antidotes should be performed as fast as possible. In general, the used nerve agent used will not be identified on the spot and emergency therapy has to be administered with standardized protocols. To this end sufficient amounts of atropine should be administered together with an oxime, at best obidoxime (250 mg i.v. or i.m), as soon as first signs and symptoms appear. This strategy should be completed by application of a benzodiazepine, e.g. diazepam or midazolam. In the hospital, especially in poisoning by persistent agents as VX continuous atropine and oxime administration, sedation and artificial ventilation may be necessary for several days.
Unfortunately, oximes will not work sufficiently in case of several nerve agents, e.g. soman or tabun. In such cases supportive care including administration of atropine and artificial ventilation are necessary.
To improve therapeutic options and especially to prevent or reduce necessity of artificial ventilation new approaches are under investigation. In order to detoxify nerve agents, small molecule scavengers and enzyme based stochiometic as well as catalytic scavengers are maters of research. Alternatively, pharmacological modulation could enable the nicotinic receptor to perform its physiological action in spite of excess acetylcholine concentration in the synaptic cleft.
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