Organophosphate Poisoning

Organophosphate compounds — including agricultural pesticides (malathion, parathion, chlorpyrifos) and military nerve agents (sarin, soman, VX) — cause toxicity by irreversibly inhibiting acetylcholinesterase (AChE), the enzyme responsible for hydrolyzing acetylcholine (ACh) at cholinergic synapses. AChE normally terminates cholinergic neurotransmission within milliseconds by breaking ACh into choline and acetate. When organophosphates phosphorylate the serine hydroxyl group at the AChE active site, ACh accumulates at all cholinergic synapses, producing sustained stimulation of muscarinic receptors (parasympathetic postganglionic sites: smooth muscle, glands, heart), nicotinic receptors (neuromuscular junction, autonomic ganglia), and central cholinergic pathways. Muscarinic overstimulation produces the DUMBBBELS toxidrome: Diarrhea, Urination, Miosis, Bradycardia, Bronchospasm/Bronchorrhea, Emesis, Lacrimation, Salivation. The 'killer B's' — Bronchospasm and Bronchorrhea — are the primary cause of death, as copious secretions flood the airways while smooth muscle constriction prevents ventilation. Nicotinic overstimulation causes muscle fasciculations progressing to depolarization block and flaccid paralysis, including respiratory muscles. A critical pharmacological concept is enzyme aging: over 24-48 hours, the organophosphate-AChE bond undergoes dealkylation, becoming permanently irreversible. Pralidoxime (2-PAM) can cleave the bond and reactivate AChE only before aging occurs, making early administration essential. Atropine...