## Pathophysiology of Organophosphate Poisoning ### Mechanism of Enzyme Inhibition **Key Point:** Organophosphates phosphorylate the serine hydroxyl group at the active site of acetylcholinesterase, forming a covalent bond. This prevents the enzyme from hydrolyzing acetylcholine, leading to its toxic accumulation. ### Cholinergic Crisis — Muscarinic vs. Nicotinic Effects Organophosphate poisoning produces a **cholinergic crisis** characterized by excessive stimulation at both receptor types: | Effect Type | Receptor | Clinical Manifestations | |---|---|---| | **Muscarinic** | M1–M5 | Miosis, bronchospasm, bronchorrhea, bradycardia, hypersalivation, lacrimation, urination, defecation | | **Nicotinic** | Skeletal muscle | Fasciculations, muscle weakness, paralysis, respiratory failure | | **CNS** | Cholinergic neurons | Anxiety, tremor, confusion, seizures, coma | **High-Yield:** In organophosphate poisoning, **cholinergic effects (both muscarinic AND nicotinic) predominate**, not anticholinergic effects. The clinical picture is one of cholinergic excess, not deficiency. ### Aging of the Enzyme Complex 1. **Initial phosphorylation** — reversible with oximes (pralidoxime) if given early (within 24–48 hours) 2. **Aging** — the phosphate-enzyme bond undergoes conformational change, becoming irreversible 3. **After aging** — oximes cannot reactivate the enzyme; only supportive care and atropine (for muscarinic blockade) remain effective **Clinical Pearl:** The window for oxime efficacy is narrow. Delayed presentation or severe poisoning may show aged enzyme, rendering oximes ineffective. **Mnemonic:** **SLUDGE** = Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis — all **muscarinic** effects of cholinergic excess. ### Why Option 2 is Wrong The question states "anticholinergic effects predominate." This is **false**. Organophosphate poisoning is a state of **cholinergic excess**, not anticholinergic effect. Anticholinergic drugs (like atropine) are used as *treatment* to block the excess acetylcholine, but the poisoning itself is fundamentally cholinergic in nature. [cite:Parikh Textbook of Forensic Medicine Ch 14]
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.