A 28-year-old pesticide worker is brought unconscious with miosis, bradycardia, excessive salivation, and urinary incontinence. Blood cholinesterase is markedly reduced. Which of the following BEST explains why pralidoxime (2-PAM) becomes ineffective if delayed beyond 24–48 hours in organophosphorus poisoning?

• A The organophosphate is metabolized to non-toxic products
• B Atropine saturates all muscarinic receptors permanently
• C Pralidoxime is hepatically cleared before it can reach the synapse
• D Aging (irreversible phosphorylation with loss of alkyl group) occurs, making the enzyme-OP complex resistant to oxime regeneration ✓

Explanation

Aging refers to the time-dependent loss of an alkyl group from the phosphorylated serine of acetylcholinesterase, converting the enzyme-OP complex into a form that cannot be reactivated by oximes. Once aging occurs (typically 24–48 hours for most OPs, faster with soman), 2-PAM is ineffective and atropine alone must be continued. Atropine acts on muscarinic receptors but does not reactivate cholinesterase. Pralidoxime is renally excreted, not rapidly hepatically cleared.

Reference: The Essentials of Forensic Medicine and Toxicology (Narayan Reddy), 34th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.