A farm worker with organophosphate insecticide poisoning reached the hospital 30 hours after exposure. Pralidoxime is administered but produces no improvement in neuromuscular function. The most likely explanation is:

• A Pralidoxime cannot cross the blood-brain barrier to reach central receptors
• B The neuromuscular weakness is now due to nicotinic receptor desensitization alone
• C Pralidoxime is inactivated by the circulating organophosphate before reaching the enzyme
• D The phosphorylated acetylcholinesterase has undergone aging and can no longer be reactivated ✓

Explanation

Organophosphates phosphorylate the serine hydroxyl of acetylcholinesterase. Over hours the conjugate loses an alkyl group, a process called aging, after which the enzyme-phosphate bond becomes resistant to oxime attack. Once aging is complete, pralidoxime is useless regardless of dose. Option C is wrong because pralidoxime is not destroyed by the poison; it simply has no substrate left to reactivate.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.