Pralidoxime

This is the oxime commonly used in Australia to reactivate acetylcholinesterase inhibition caused by organophosphates (OPs). There is a significant debate regarding the effectiveness of pralidoxime in OP and carbamate poisoning and it probably relates to timing, dosing and the OP/Carbamate involved. If you are giving pralidoxime please consult your toxicologist for the latest evidence.

Mechanism of action:

Pralidoxime reactivates acetylcholinesterase only if irreversible binding to the OP has not already occurred (“ageing”). The acetylcholinesterase enzyme has two parts to it.  In organophosphate poisoning, an organophosphate binds to just one end of the acetylcholinesterase enzyme (the esteric site), blocking its activity. Pralidoxime is able to attach to the other half (the unblocked, anionic site) of the acetylcholinesterase enzyme. It then binds to the organophosphate, the organophosphate changes conformation, and loses its binding to the acetylcholinesterase enzyme. The conjoined poison / antidote then unbinds from the site, and thus regenerates the enzyme, which is now able to function again.

Administration:

• Administer the initial dose of 2 g pralidoxime in 100 ml of 0.9% saline IV over 15 minutes (rapid administration can cause neuromuscular blockade and laryngospasm). Then….
• Commence pralidoxime infusion at 500 mg/hour (pralidoxime 6 g in 500 ml of 0.9% saline at 42 ml/hour).
• Occasionally higher infusion rates will be required.
• Paediatric dose = initial dose of 25-50 mg/kg followed by an infusion of 10-20 mg/kg/hour.
• The infusion can be discontinued after 24 hours if the patient is well. The patient will require close observation for 24 hours and if toxicity reoccurs they will need another 24 hours of therapy.
• Alternatively if red cell anticholinesterase activity assays can be done then these can be tested 4 hours post cessation of the infusion. If activity is maintained, pralidoxime is no longer required.

References

• Buckley NA. Eddleston M. Szinicz L. Oximes for acute organophosphate pesticide poisoning. Cochrane Database of Systematic Reviews 2005(1):CD005085.
• Eddleston M, Eyer P, Worek F et al.  Pralidoxime in acute organophosphorus insecticide poisoning – a randomised controlled trial.  PLoS Med. 2009 June; 6(6):e1000104. Published online 2009 June 30.