The clinical presentation of severe nerve-agent poisoning overlaps with that of severe cyanide poisoning, though nerve agents may produce cholinergic effects and are more likely to produce cyanosis Hemodynamic effects may be either excitatory or inhibitory, depending on balance between sympathomimetic and muscarinic effects Nerve-agent poisonings generally require atropine to counter the cholinergic effects, as well as pralidoxime to counter the neuromuscular effects Prophylactic treatment with benzodiazepines to prevent seizures is indicated in large exposures Nerve agents (including the compounds sarin, soman, tabun, and VX) are organophosphorus esters and, like the less potent “organophosphate” (OP) insecticides, are potent and essentially irreversible inhibitors of acetylcholinesterase (see Chapter 102 Toxicologic Emergencies ) Certain oximes can dissociate bound nerve agents from acetylcholinesterase but only initially; after a variable period a portion of an alkyl group is nonenzymatically lost from the enzyme in a process called aging, and the resulting nerve agent— cholinesterase complex becomes refractory to oxime action The time required for these agents to undergo aging varies from a few minutes for soman to 48 hours for VX Nerve-agent vapors are heavier than air and would thus affect persons closer to the ground (e.g., young children) disproportionately Toxicology Nerve agent–induced inhibition of acetylcholinesterase causes the neurotransmitter acetylcholine to accumulate in cholinergic synapses and in neuromuscular and neuroglandular junctions; this excess of acetylcholine initially causes end-organ stimulation that may then lead to end-organ failure Cholinergic sites are found in the central nervous system (CNS), in the neuromuscular junctions of somatic nerves, in parasympathetic nerve endings, in some sympathetic nerve endings (e.g., sweat glands), and in both parasympathetic and sympathetic ganglia The cholinergic syndrome thus produced is classically divided into CNS effects, nicotinic effects (at neuromuscular junctions and sympathetic ganglia), and muscarinic effects (in smooth muscles and exocrine glands) CNS effects include altered mental status progressing through lethargy to coma, ataxia, convulsions, and respiratory depression (central apnea) Nicotinic effects include muscle fasciculations (including tics) and twitching, and then weakness