Which of the following is the primary mechanism by which organophosphate compounds cause toxicity?

Explanation

## Mechanism of Organophosphate Toxicity **Key Point:** Organophosphates irreversibly phosphorylate the anionic site of acetylcholinesterase (AChE), preventing hydrolysis of acetylcholine (ACh) and causing its accumulation at synapses and neuromuscular junctions. ### Pathophysiology Organophosphates form a covalent bond with the serine residue in the active site of AChE. This phosphorylation is initially reversible but rapidly becomes irreversible through a process called "aging," where the phosphoryl-enzyme complex loses an alkyl group and becomes resistant to reactivation. **High-Yield:** The accumulation of ACh at both muscarinic and nicotinic receptors produces the characteristic toxidrome: - **Muscarinic effects** (SLUDGE): Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis - **Nicotinic effects**: Muscle fasciculations, paralysis, tachycardia, hypertension (early) - **CNS effects**: Anxiety, tremor, seizures, coma ### Why Other Options Are Wrong Direct receptor blockade (option B) would not explain the cholinergic crisis seen in organophosphate poisoning. Monoamine oxidase inhibition (option C) is not the primary mechanism and does not account for the muscarinic and nicotinic manifestations. Competitive antagonism (option D) is the opposite of what occurs — there is excess ACh, not blockade. [cite:Harrison 21e Ch 473]