title: Pharmacologic prophylaxis against nerve agent poisoning.
abstract: Nerve agent poisoning is characterized by the rapid progression of toxic signs, including hypersecretions, tremor, convulsions and profound brain damage. In the political arena of today's world, the threat of nerve agent use against military troops has prompted armies to search for prophylactic protection. The two main strategies for prophylaxis include biological scavengers that can bind or cleave nerve agents before they react with acetylcholinesterase, and antidotes as prophylactic treatment. Pyridostigmine is the current pretreatment for nerve agent poisoning and is in use by most of the armed forces in Western countries. However, since pyridostigmine barely crosses the blood-brain barrier it provides no protection against nerve agent-induced central injury. Pyridostigmine is ineffective when administered without post-exposure treatment adjuncts. Therefore, other directions for prophylactic treatment should be explored. These include combinations of carbamates (reversible AChE inhibitors) and central anticholinergics or NMDA receptor antagonists, benzodiazepines or partial agonists for benzodiazepine receptor, and other central AChE inhibitors approved for Alzheimer's disease. The transdermal route is an alternative way for delivering the prophylactic agent. Administration of prophylaxis can be extended also for civilian use during wartime.
authors.affiliation: Chemical, Biological, Nuclear and Radiological Medicine Branch, Medical Corps, Israel Defense Force. Amitay2@zahav.net.il
authors.forename: Ido
authors.initials: I
authors.lastname: Layish
authors.forename: Amir
authors.initials: A
authors.lastname: Krivoy
authors.forename: Eran
authors.initials: E
authors.lastname: Rotman
authors.forename: Arseny
authors.initials: A
authors.lastname: Finkelstein
authors.forename: Zeev
authors.initials: Z
authors.lastname: Tashma
authors.forename: Yoav
authors.initials: Y
authors.lastname: Yehezkelli
mesh_terms: D000931:Antidotes / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D011729:Pyridostigmine Bromide / Q000627:therapeutic use
chemical_list: D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide