Nerve agents typically refer to a subgroup of drugs in the class of organophosphates (OP). Among these are Tabun (GA), Sarin (GB), Soman (GD, isopropyl methyl phosphonofluoridate), Cyclosarin (GF), VX, and VR. These compounds can be irreversible inhibitors of acetylcholinesterase (AChE) after a certain time has been reached, usually referred to as aging half-time. Aging times can be as short as 2 minutes for Soman, moderate like sarin at 5 hours or as long as Tabun or VX at 40 hours. After 5 half-times, over 95% of enzyme activity would be inhibited. In addition, butyrylcholinesterase and neurotoxic esterase can be inhibited leading to prolongation of succinylcholine and neuroexcitatory symptoms such as seizures.
Symptoms are predominantly cholinergic with salivation, lacrimation, miosis, nausea/vomiting, disorientation and can include confusion, bronchoconstriction, bradycardia, asystole, neuromuscular weakness and complete respiratory failure if severe.
Initial treatment involves triage and decontamination. Removal of clothing and washing helps to reduce additional absorption of persistent drug (Tabun, VX, VR) as well as protect health care providers. These agents can penetrate clothing, skin and leather. Rubber and polyethylene are more resistant but can still be penetrated.
After decontamination, symptomatic management is started. If respiratory support is required, intubation and mechanical ventilation is performed. Atropine is the primary medical management for exposure and control of the cholinergic symptoms. Starting dose of atropine is 2 mg and can be repeated as needed (up to doses of 50-200 mg) until symptoms are under control and heart rate is greater than 80 bpm. Severe cases can require atropine infusions. Benzodiazepines are used for disorientation and seizures.
Oximes are a class of medications that can reactivate AChE-OP complexes if given after exposure but before aging is complete. The most common oxime in the United States is pralidoxime (2-PAM, 2-pyridine aldoxime methyl chloride); whereas, obidoxime is more common internationally.
In military settings where nerve agent exposures are expected, pretreatment with pyridostigmine can be used. By having a reversible complex with AChE, in the event of a potentially lethal dose of OP, the action of the irreversible inhibitor is blocked in a competitive pattern and a reserve of enzyme is effectively auto-transfused into the patient during the subsequent period when the reversible inhibitor-AChE complex breaks down. Physostigmine is another reversible AChE inhibitor that uniquely crosses the blood brain barrier. It is not FDA approved for pretreatment like pyridostigmine but has been found to be more effective in preventing in reducing mortality in animal studies, with the caveat of increased side effects of delirium, visual disturbances.
- Lorke DE, Petroianu GA. Reversible cholinesterase inhibitors as pretreatment for exposure to organophosphates. A Review. J Applied Toxicology. 2018. PubMed Link
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