Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning.

Abstract

Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers.

An In Vivo Zebrafish Screen Identifies Organophosphate Antidotes with Diverse Mechanisms of Action

“…Drugs such as atropine antagonize cholinergic receptors, countering the effects of acetylcholine accumulation, but their toxicity limits their use. 4,10 2-PAM, often used in conjunction with atropine, is an AChE reactivator. Organophosphates inhibit AChE by covalently linking a phosphoryl group to the enzyme’s active site serine hydroxyl group.…”

“…Furthermore, toxicity associated with 2-PAM administration could lead to dangerous hypertension and tachycardia. 10 The development of additional antidotes that work via other mechanisms might therefore substantially improve clinical care and safety. 1,4,13 …”

Changing the scale and efficiency of chemical warfare countermeasure discovery using the zebrafish

“…Failure to metabolize acetylcholine near cholinergic receptor sites causes continuous stimulation of cholinergic neurons in the central and peripheral nervous systems. Atropine antagonizes cholinergic receptors, and by so doing, it counteracts the effects of acetylcholine accumulation 48, 49 . Unfortunately, it remains difficult to deliver sufficient atropine to antagonize the excess acetylcholine without causing toxicity from too much cholinergic antagonism.…”

“…Unfortunately, it remains difficult to deliver sufficient atropine to antagonize the excess acetylcholine without causing toxicity from too much cholinergic antagonism. Pralidoxime (2-PAM), an acetylcholinesterase reactivator, exhibits toxicities of its own including dangerous hypertension and tachycardia 48 . Its use is further limited by the fact that some organophosphates sterically hinder 2-PAM from reactivating the inhibited AChE.…”

Biochemical terrorism: the medical threat in the twenty-first century*1

“…Specific antidotes exist only against nerve agents, cyanide, and lewisite. For other offending agents, treatment is supportive and directed at treating the associated complications (22).…”