A patient with organophosphate poisoning is treated with atropine and pralidoxime. Which statement best explains why pralidoxime must be given within 24–48 hours of exposure?
- A Aging of the organophosphate-AChE complex results in loss of the phosphoryl group's nucleophilic susceptibility, making reactivation impossible ✓
- B After 48 hours, pralidoxime itself becomes toxic and causes irreversible acetylcholinesterase inhibition
- C Pralidoxime is rapidly metabolised by plasma cholinesterase within 24 hours and loses its efficacy
- D Acetylcholinesterase undergoes proteolytic degradation after 48 hours and cannot be reactivated regardless of treatment
Correct answer: A. Aging of the organophosphate-AChE complex results in loss of the phosphoryl group's nucleophilic susceptibility, making reactivation impossible
Explanation
Aging refers to a secondary reaction in which the organophosphate-AChE adduct undergoes dealkylation, converting the phosphorylated enzyme into a stable, oxime-resistant form. Once aging occurs (within 24–48 hours for most organophosphates), pralidoxime cannot regenerate the active enzyme. Pralidoxime itself is not toxic in this context, and the enzyme is not proteolytically degraded.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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