Organophosphate Poisoning

Organophosphates phosphorylate and inactivate acetylcholinesterase (AChE), the enzyme that normally terminates acetylcholine (ACh) signalling. ACh then accumulates at muscarinic receptors, nicotinic receptors in autonomic ganglia and the neuromuscular junction, and cholinergic pathways in the central nervous system. The resulting picture is not a single uniform pattern. Muscarinic excess produces bronchorrhoea, bronchospasm, salivation, lacrimation, sweating, miosis, vomiting, diarrhoea, urination, bradycardia, and increased gastrointestinal motility. Nicotinic excess produces fasciculations, weakness, hypertension or tachycardia, and eventually neuromuscular transmission failure. Central effects range from anxiety and agitation to seizures, coma, and respiratory depression. The patient may therefore be bradycardic from muscarinic stimulation while also developing tachycardia or hypertension from nicotinic ganglionic effects. The airway findings carry the greatest immediate danger. Copious bronchial secretions, bronchospasm, aspiration, and weakness of the respiratory muscles can combine into fatal respiratory failure. A patient with a wet chest, worsening oxygenation, and visible fasciculations needs airway and antidote treatment even if the pupils are not markedly constricted. AChE that has been phosphorylated can initially be reactivated by an oxime. With time, the enzyme undergoes aging, a chemical change that prevents...