Question of the Week
November 22, 2010
Why is pralidoxime used for organophosphate poisonings?
Organophosphates are class of xenobiotics which are available as insecticides; however, certain organophosphates are considered chemical warfare agents. “Nerve agents” are extremely potent organophosphates and examples include sarin, tabun, soman, and VX. The mechanism of action of these compounds is the same. They bind to acetylcholinesterase which is the enzyme responsible for breaking down acetylcholine. Acetylcholine is the neurotransmitter for muscarinic and nicotinic cholinergic receptors. As a result of the binding of the organophosphate, acetylcholinesterase is disabled and the resulting clinical effect is the cholinergic toxidrome.
In addition to adequate decontamination of the exposed patient, the mainstay of therapy is the drying of the secretions from the cholinergic effects. Atropine which is an antimuscarinic agent is given intravenously until the secretions (particularly bronchial secretions) are improved; however, atropine does not treat the nicotinic effects, nor does it reverse the binding of the organophosphate to the acetylcholinesterase. Pralidoxime is able to reactivate the acetylcholinesterase by essentially removing the organophosphate from the enzyme. This regenerates the enzyme and its function; however, pralidoxime must be administered early, as the bond between the organophosphate and the acetylcholinesterase can become permanent (known as “ageing”). Once the “ageing” occurs, pralidoxime is not beneficial and the patient will continue to have a cholinergic toxidrome until neurons are regenerated (weeks to months).
Question prepared by: Saralyn Williams, MD Medical Toxicologist