Pretreatment for Nerve Agent Exposure

PYRIDOSTIGMINE, A PERIPHERALLY ACTING CARBAMATE COMPOUND Efficacy Safety 

Colonel, Medical Corps, U.S. Army Director, Clinical Consultation, Office of the Assistant Secretary of Defense (Health Affairs), Washington, D.C. 20301-1200 formerly, Commander, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425 

Nerve agents are rapidly acting chemical compounds that can cause respiratory arrest within minutes of absorption. Their speed of action imposes a need for rapid and appropriate reaction by exposed soldiers, their buddies, or medics, who must administer antidotes quickly enough to save lives. A medical defense against nerve agents that depends completely on postexposure antidote treatment, however, has two key limitations  

Organophosphate nerve agents inhibit the active site of AChE, a key enzymatic regulator of cholinergic neurotransmission. As noted in Chapter 5, Nerve Agents, agent-bound AChE can be reactivated by a class of antidote compounds, the oximes, which remove the nerve agent molecule from the catalytic site of AChE. 

Aging is an irreversible reaction. After dealkylation, an AChE-bound nerve agent molecule can no longer be removed from the enzyme by an oxime. Thus, aging of enzyme-bound nerve agent prevents oxime antidotes from reactivating AChE. This is an extremely difficult problem in the 

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Pyridostigmine About twelve years ago, the U. S. military provided pyridostigmone bromide as a pretreatment for nerve agent exposure. Each trooper received a blister pack... 

Pyridostigmine About twelve years ago, the U.S. military provided pyridostigmone bromide as a pretreatment for nerve agent exposure. Each trooper received a blister pack containing twenty-one 30-mg tablets for a dose regimen of one 30-mg tablet every eight hours. When given before soman exposure and when that exposure is followed by the standard MARK I therapy, the use of this pretreatment will increase the LD-50 several fold over the LD-50 obtained without the use of the pretreatment. When soman is the nerve... 

Dunn, M.A., Hackley, B.E., Sidell. F.R. (1997). Pretreatment for nerve agent exposure. In Medical Aspects of Chemical and Biological Warfare (F.R. Sidell, E.T. Takafuji, D.R. Franz, eds), pp. 181-96. Office of the Surgeon General, Walter Reed Army Medical Center, Washington, DC. 

Miosis, pain, dim vision, and nausea can be relieved by topical atropine in the eye. Pretreatment with carbamates may protect the cholinesterase enzymes before nerve agent exposure. Pyridostigmine bromide is available as a pretreatment for nerve agent exposure. It is available in 30 mg tablets tablets should be administered every 8h. When used prior to exposure, it should be followed by atropine and pralidoxime chloride after exposure. 

Dunn, MA, BE Hackley, FR Sidell. 1997. Pretreatment for nerve agent exposure. In Sidell FR, Takafuji ET, Franz DR (Eds). Textbook ofMilitary Medicine Part I, Warfare, Weaponry, and the Casualty Medical Aspects of Chemical and Biological Warfare. Washington, DC Office of the Surgeon General, Department of the Army, United States of America. Pp. 181-196. 

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