Pathophysiological and clinical aspects of combat anticholinesterase poisoning

Nerve agents are organophosphate compounds similar to those used as pesticides but with much higher toxicity. They all block the activity of the enzyme acetylcholine esterase. Victims are intoxicated by absorption of the toxin via exposed skin or, more commonly, via inhalation of the poisonous gas. The resultant clinical picture is of hyperstimulation of both the nicotinic and muscarinic cholinergic system, which, if not promptly treated, leads to severe muscle paralysis, cardiac brady-asystole, hypersecretion from secretory glands, respiratory failure, seizures, coma and death. If antidotal drugs are promptly administered, the clinical severity of the poisoning is attenuated or complete abortion of symptoms is obtained. The main therapeutic strategies include atropine and oximes that counteract the nerve-agent-induced muscarinic and nicotinic cholinergic symptoms, respectively. Anticonvulsants and sedatives are used to treat central nervous system acetylcholine esterase disarray. This review summarizes the biochemistry and pathophysiology of anticholinesterase poisoning, the relevant clinical manifestations and the currently available therapeutic strategies.