A patient with organophosphate poisoning is treated with atropine plus pralidoxime. The primary biochemical reason pralidoxime must be given within 24–48 hours of poisoning is:
- A Pralidoxime loses its ability to penetrate the blood–brain barrier after 24 hours
- B Organophosphate is fully excreted by 48 hours, making pralidoxime redundant
- C Acetylcholinesterase undergoes 'aging' — irreversible dealkylation — rendering oxime-mediated reactivation impossible ✓
- D Pralidoxime is metabolised to a toxic aldehyde after 48 hours of storage in plasma
Correct answer: C. Acetylcholinesterase undergoes 'aging' — irreversible dealkylation — rendering oxime-mediated reactivation impossible
Explanation
After organophosphate binds acetylcholinesterase, the phosphorylated enzyme undergoes 'aging' — spontaneous dealkylation that converts the P–O bond to one that is no longer susceptible to nucleophilic attack by oximes such as pralidoxime. This process is time-dependent (within 24–48 hours for most OP compounds), hence early administration of pralidoxime is essential. Atropine counters muscarinic excess but does not reactivate the enzyme. Pralidoxime does not appreciably enter the CNS and addresses peripheral NMJ effects primarily.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.