3 Clinical psychopharmacology3.3 Pharmacodynamics
3.3.6.1 Antimuscarinics
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Written by Resident Doctor Committee · Published
Muscarinic blockade
Procyclidine, trihexyphenidyl and benzatropine competitively block muscarinic receptors, not nicotinic channels.
Blockade produces the opposite of cholinergic stimulation, and poor subtype selectivity brings both peripheral and central harms.
Site | Effect of blockade |
|---|---|
Eye | Mydriasis, cycloplegia (loss of near focus) |
Salivary glands | Dry mouth |
Gut | Constipation, ileus |
Bladder | Urinary retention |
Heart | Sinus tachycardia |
Sweat glands | Absent sweating, hot dry skin, hyperthermia |
Brain | Poor attention and memory, then delirium |
Narrow-angle glaucoma risks acute angle closure.
Extrapyramidal side effects
Striatal D2 blockade leaves a relative cholinergic excess, which centrally acting antimuscarinics damp.
Acute dystonia responds to procyclidine 5 to 10 mg intramuscularly or intravenously, often within minutes.
Antimuscarinics can worsen tardive dyskinesia and are not routine treatment for akathisia.
Antihistamines
First-generation antihistamines (promethazine, diphenhydramine) are poorly selective and have substantial central antimuscarinic activity.
They can therefore counter extrapyramidal effects, but they readily cause delirium in older people.
Second-generation antihistamines are highly H1-selective and largely lack this activity.
Anticholinergic delirium
Oxybutynin carries a high central anticholinergic burden and is the drug most likely to cause delirium, especially in older or cognitively vulnerable patients.
Older age, dementia, Parkinson's disease, prior delirium and polypharmacy increase vulnerability.
Total burden adds up across tricyclics, antihistamines, bladder drugs and over-the-counter sleep remedies.
Management starts with stopping the causative antimuscarinics, not adding medication, and physostigmine needs specialist toxicology advice first.