injuries poisoning
Nerve Chemical Warfare Agents
Pathophysiology of Nerve Chemical Warfare Injuries
Nerve agents inhibit the enzyme acetylcholinesterase (AChE), which hydrolyzes the neurotransmitter acetylcholine (ACh) once ACh has finished activating receptors in neurons, muscles, and glands. Inhibition of AChE leads to an excess of ACh at all of its receptors (cholinergic crisis), first causing increased activity of the affected tissue, followed eventually in the CNS and in skeletal muscle by fatigue and failure of the tissue. Nerve agents inhibit both muscarinic and nicotinic ACh receptors. Muscarinic ACh receptors are present in the central nervous system (CNS), autonomic ganglia, smooth-muscle fibers, and exocrine glands; nicotinic ACh receptors are present in skeletal muscle. The binding of nerve agent to AChE is essentially irreversible without treatment; treatment with an oxime can regenerate the enzyme as long as the bond has not been further stabilized (a process termed aging) over time. Most nerve agents, like organophosphate insecticides, take hours to age fully, but GD (soman) can age essentially completely within 10 minutes of binding. 