A patient is on an irreversible cholinesterase inhibitor. Which feature of the resulting cholinesterase inhibition is MOST important in determining the duration of toxic effects?

• A The half-life of circulating acetylcholine
• B The rate of synthesis of new acetylcholinesterase ✓
• C The renal excretion rate of the organophosphate metabolite
• D The rate of spontaneous reactivation of the enzyme

Explanation

Irreversible cholinesterase inhibitors (organophosphates) permanently phosphorylate the serine at the active site of AChE; recovery depends entirely on the synthesis of new enzyme molecules, which takes weeks. Spontaneous reactivation (option D) is negligible with aged phosphorylated enzyme. Renal clearance of metabolites matters for duration of exposure but not for enzyme recovery. ACh half-life is a consequence, not a determinant.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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