Foundations · Year 1 · from Foundations
Case 3: Organophosphate Poisoning (Irreversible Enzyme Inhibition)
Clinical Image
Source: Wikipedia - Organophosphate poisoning - CC BY-SA 4.0
Case Presentation
A 32-year-old agricultural worker is brought to the emergency department after being found confused and salivating excessively in a field where pesticides were recently applied. His coworkers noted he was not wearing protective equipment. On examination, he has pinpoint pupils (miosis), profuse sweating, excessive salivation and lacrimation, bronchorrhea with audible wheezing, bradycardia (heart rate 48), and fasciculations of facial and limb muscles. He is also incontinent of urine. These findings represent the classic cholinergic toxidrome (SLUDGE/BBB: Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis, Bradycardia, Bronchospasm, Bronchorrhea). He is immediately treated with IV atropine to block muscarinic effects and pralidoxime (2-PAM) to reactivate acetylcholinesterase before irreversible "aging" of the enzyme occurs. Pralidoxime must be given within hours because after aging, the organophosphate-enzyme bond becomes permanent and no antidote can restore function. The patient improves over 48 hours with supportive care.
Key Learning Points
- Organophosphate pesticides and nerve agents are irreversible inhibitors of acetylcholinesterase, covalently phosphorylating the active site serine residue
- Unlike reversible inhibitors, irreversible inhibitors permanently inactivate enzymes; recovery requires synthesis of new enzyme molecules
- Pralidoxime can reactivate the enzyme only before "aging" (dealkylation of the organophosphate-enzyme complex), which occurs within hours; this time-sensitive treatment illustrates the clinical importance of understanding enzyme inhibition kinetics