Anticholinergic

Anticholinergic refers to the property of a medicine that blocks the action of acetylcholine - one of the body's most important neurotransmitters - at muscarinic receptors. Acetylcholine drives parasympathetic nervous system activity ('rest and digest'), so blocking it produces a characteristic set of effects: dry mouth, blurred vision, dilated pupils, urinary retention, constipation, decreased sweating, tachycardia, and at higher doses confusion, agitation, and delirium. Memorized in medical training as 'dry as a bone, red as a beet, hot as a hare, blind as a bat, mad as a hatter,' this toxidrome captures the systemic impact of muscarinic blockade.

Anticholinergic medicines include those intentionally designed for this effect - atropine for bradycardia, ipratropium and tiotropium for COPD, oxybutynin and tolterodine for overactive bladder, scopolamine for motion sickness, and glycopyrrolate to reduce secretions. But many other commonly used medicines have anticholinergic side effects as an incidental property: tricyclic antidepressants (amitriptyline, nortriptyline), first-generation antihistamines (diphenhydramine, hydroxyzine), some antipsychotics (olanzapine, clozapine), antiparkinsonian agents (benztropine), and many over-the-counter sleep and cold remedies.

Clinically, the anticholinergic burden is a critical concept in geriatrics. Older adults are particularly sensitive to anticholinergic effects because of age-related decline in cholinergic neurons and increased blood-brain barrier permeability. Cumulative anticholinergic exposure increases the risk of falls, cognitive impairment, delirium, and even dementia. The Beers Criteria explicitly recommends avoiding strong anticholinergics in patients over 65, and clinical tools such as the Anticholinergic Cognitive Burden (ACB) scale help quantify this risk.

A common misconception is that only medicines labeled 'anticholinergic' carry this risk. Patients often take multiple medications - each with mild anticholinergic activity - which together produce significant cumulative impact. Another misconception is that the effects are limited to a dry mouth. Severe anticholinergic toxicity can produce hyperthermia, seizures, urinary retention with bladder rupture, and life-threatening tachycardia, especially in overdose with tricyclic antidepressants or diphenhydramine.

Management of toxicity is largely supportive - cooling, fluids, benzodiazepines for agitation, and monitoring. Physostigmine, a cholinesterase inhibitor, can reverse severe central anticholinergic delirium but carries its own risks. Prescribers should review the anticholinergic burden of every patient over 65, deprescribe where possible, and counsel patients to avoid stacking OTC antihistamines on top of prescription anticholinergics.

Deprescribing strategies for anticholinergic burden focus on identifying medicines that can be substituted with safer alternatives - mirabegron instead of oxybutynin for overactive bladder, second-generation antihistamines instead of diphenhydramine for allergies, melatonin or trazodone instead of antihistamines for insomnia, citalopram or sertraline instead of paroxetine (which has significant anticholinergic activity) for depression in the elderly. The Beers Criteria, STOPP/START criteria, and the Anticholinergic Burden Scale provide frameworks for this work. Beyond individual medicines, the cumulative anticholinergic burden over years of polypharmacy is increasingly recognized as a modifiable contributor to age-related cognitive decline, falls, and functional loss.