Toxicology of Muscarinic Antagonists

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 Toxicology of Muscarinic Antagonists


Sources of Antimuscarinic Poisoning

Sources of poisoning include natural products (e.g., Atropa belladonna, Datura stramonium), selective antimuscarinic drugs (e.g., atropine, scopolamine), and other drugs with pronounced antimuscarinic properties (e.g., antihistamines, phenothiazines, tricyclic antidepressants).


Symptoms

Symptoms of antimuscarinic poisoning, which are the direct result of excessive muscarinic blockade, include dry mouth, blurred vision, photophobia (secondary to mydriasis), hyperthermia, CNS effects (hallucinations, delirium), and skin that is hot, dry, and flushed. Death results from respiratory depression secondary to blockade of cholinergic receptors in the brain.


Treatment

Treatment consists of (1) minimizing intestinal absorption of the antimuscarinic agent and (2) administering an antidote. Minimizing absorption is accomplished by administering activated charcoal, which will adsorb the poison within the intestine, thereby preventing its absorption into the blood. The most effective antidote to antimuscarinic poisoning is physostigmine, an inhibitor of acetylcholinesterase. By inhibiting cholinesterase, physostigmine causes acetylcholine to accumulate at all cholinergic junctions. As acetylcholine builds up, it competes with the antimuscarinic agent for receptor binding, thereby reversing excessive muscarinic blockade.


Warning

It is important to differentiate between antimuscarinic poisoning, which often resembles psychosis (hallucinations, delirium), and an actual psychotic episode. We need to make the differential diagnosis because some antipsychotic drugs have antimuscarinic properties of their own, and hence will intensify symptoms if given to a victim of antimuscarinic poisoning. Fortunately, because a true psychotic episode is not ordinarily associated with signs of excessive muscarinic blockade (e.g., dry mouth, hyperthermia, dry skin), differentiation is not usually difficult.

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