Pralidoxime is most effective in organophosphate poisoning only when administered within hours of exposure. The reason for this narrow window is:

• A Pralidoxime undergoes rapid hepatic metabolism to inactive metabolites
• B The organophosphate-enzyme complex undergoes aging, becoming resistant to reactivation ✓
• C Atropine competitively displaces pralidoxime from the active site
• D Regenerated acetylcholinesterase is rapidly degraded by proteases

Explanation

Organophosphates phosphorylate the serine hydroxyl group of acetylcholinesterase. Initially this bond can be cleaved by pralidoxime, regenerating active enzyme. With time one alkyl group is lost from the phosphorylated enzyme, a process called aging, which makes the bond irreversible and refractory to oximes. Aging is fastest with soman, hence pralidoxime is useless there if delayed. Option A is wrong because pralidoxime is largely excreted unchanged by the kidney; the limitation is chemical, not kinetic.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.