An 82-year-old woman taking diphenhydramine nightly for sleep is brought in with confusion, dry flushed skin, dilated pupils and urinary retention. The toxidrome and its underlying pharmacological basis are:

• A Cholinergic crisis due to acetylcholinesterase inhibition
• B Extrapyramidal reaction due to dopamine receptor blockade
• C Serotonin syndrome due to 5-HT2A agonism
• D Anticholinergic delirium due to central muscarinic receptor blockade ✓

Explanation

First-generation H1 antihistamines such as diphenhydramine cross the blood-brain barrier and block central muscarinic receptors, producing the classic anticholinergic toxidrome: mydriasis, dry skin, urinary retention, tachycardia and delirium, summarised as blind as a bat, hot as a hare, dry as a bone, mad as a hatter. Elderly patients are especially susceptible. Physostigmine reverses the central features. Serotonin syndrome and extrapyramidal reactions are not produced by muscarinic antagonism.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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Written and medically reviewed by the StethoPrep medical team.