Question of the Week
November 29, 2010
Why does pralidoxime (2PAM) NOT work for patients poisoned with carbamates?
Carbamates are a class of central nervous system agents which bind to and inactivate acetylcholinesterase. Although we commonly think of them as insecticides and link them with organophosphates, they are also used in clinical medicine. Examples include neostigmine, pyridostigmine, and physostigmine. These are derivatives of carbamic acid, hence the name carbamates. There are other therapeutic agents that have a similar mechanism of action but are not carbamates. Examples include edrophonium.
Carbamates tend not the cross the blood brain barrier but can still cause a cholinergic crisis in the poisoned patient. Atropine is a mainstay of treatment. Carbamates have a different structure than organophosphates and thus pralidoxime does not bind to them. Thus, pralidoxime has no efficacy for a carbamate poisoned patient. The difficulty is that the cholinergic toxidrome looks similar to organophosphate poisoning and most patients can’t tell you which one is the causative agent. As a result, most patients with acute cholinergic poisoning from an undefined toxicant are treated with pralidoxime.
There is good news. The carbamate-acetylcholinesterase bond is not stable and the carbamate spontaneously will unbind. This reactivates acetylcholinesterase and resolution of the toxidrome occurs. No “aging” of the bond occurs.
Question prepared by: Saralyn Williams, MD Medical Toxicologist