## Mechanism of Organophosphate Toxicity **Key Point:** Organophosphates irreversibly phosphorylate the serine residue at the active site of acetylcholinesterase (AChE), preventing the breakdown of acetylcholine. ### Pathophysiology 1. Organophosphates form a covalent bond with the esterase site of AChE 2. This prevents hydrolysis of acetylcholine at both nicotinic and muscarinic synapses 3. Acetylcholine accumulates in the synaptic cleft 4. Excessive stimulation of both muscarinic and nicotinic receptors occurs ### Clinical Consequence The resulting cholinergic crisis manifests with: - **Muscarinic signs:** SLUDGE (Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis), bradycardia, bronchospasm, miosis - **Nicotinic signs:** Muscle fasciculations, paralysis, weakness **High-Yield:** The diagnosis is confirmed by measuring red blood cell (RBC) cholinesterase levels, which are markedly depressed in organophosphate poisoning. **Clinical Pearl:** The degree of AChE inhibition correlates with clinical severity — >50% inhibition causes symptoms; >90% inhibition is life-threatening. 
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