Antimuscarinic Drugs

Antimuscarinic drugs competitively block acetylcholine at muscarinic receptors and so reduce parasympathetic effects. They are used for bradycardia, secretion control, gut spasm, overactive bladder, parkinsonism and drug-induced dystonia, motion sickness, and eye examination.

Classification. Tertiary amines that enter the brain (atropine, hyoscine hydrobromide, benzatropine, trihexyphenidyl, oxybutynin, tolterodine). Quaternary amines with little central effect (hyoscine butylbromide, glycopyrronium, ipratropium, tiotropium, trospium, propantheline). Eye agents: tropicamide, cyclopentolate. Bladder-selective agents: solifenacin, darifenacin (more M3 selective), fesoterodine.

Mechanism. Reversible competitive blockade at M1 to M5. Blocking M2 on the heart removes vagal tone and raises heart rate. M3 blockade reduces secretions, smooth muscle tone and pupil constriction. Very low atropine doses can slow the heart briefly, probably through central or presynaptic M1 effects.

Organ effects. Tachycardia, mydriasis, cycloplegia, dry mouth, reduced bronchial secretions and mild bronchodilation, reduced gastric and gut motility, urinary retention, reduced sweating with raised body temperature, and in the brain confusion, agitation and amnesia.

Pharmacokinetics. Atropine has a half-life of about 2 to 4 hours, and effects on the eye persist for days. Quaternary agents are poorly absorbed orally. Oxybutynin undergoes extensive first pass metabolism to an active metabolite that causes dry mouth. Transdermal hyoscine releases drug steadily over 72 hours.

• Atropine: nonselective; intravenous for bradycardia and organophosphate poisoning; ophthalmic for cycloplegia and uveitis.
• Hyoscine butylbromide: antispasmodic for colic; does not enter the brain; poor oral absorption.
• Hyoscine hydrobromide: motion sickness and terminal secretions; sedating; amnesic.
• Glycopyrronium: antisialagogue before anaesthesia; no central effects; also used in COPD by inhalation.
• Ipratropium, tiotropium: inhaled bronchodilators.
• Oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine, trospium: overactive bladder. Trospium and darifenacin have the least central penetration; oxybutynin the most.
• Benzatropine, trihexyphenidyl: parkinsonism and acute dystonia.
• Tropicamide, cyclopentolate: short-acting mydriatics for examination.

• Symptomatic bradycardia: atropine 500 micrograms intravenously, repeated every 3 to 5 minutes to a total of 3 mg. Some schedules start with 1 mg. Ineffective in heart transplant recipients and may worsen infranodal block.
• Intestinal or biliary colic: hyoscine butylbromide 20 mg intravenously, intramuscularly or subcutaneously, repeated after 30 minutes if needed, to a maximum of 100 mg in 24 hours.
• Terminal respiratory secretions: hyoscine butylbromide 20 mg subcutaneously, then 60 to 120 mg over 24 hours by syringe driver. Glycopyrronium is an alternative.
• Antisialagogue premedication: glycopyrronium 4 to 5 micrograms/kg intravenously.
• Overactive bladder: solifenacin 5 mg daily, increased to 10 mg; oxybutynin 5 mg 2 to 3 times daily, maximum 5 mg 4 times daily. Prefer agents with less central penetration in older adults. A beta-3 agonist is an alternative where anticholinergic burden is a concern.
• Acute dystonia: benzatropine 1 to 2 mg intravenously or intramuscularly, with response expected within minutes.
• Eye: tropicamide 0.5% to 1% gives mydriasis for 4 to 6 hours. Atropine 1% gives cycloplegia that can last 7 to 14 days.
• Motion sickness: hyoscine hydrobromide patch applied several hours before travel.

Contraindications. Narrow-angle glaucoma, urinary retention or prostatic obstruction, paralytic ileus, toxic megacolon, severe ulcerative colitis, myasthenia gravis, tachyarrhythmia, gastro-oesophageal obstruction and gastroparesis. Hyoscine butylbromide is avoided in unrecognised tachycardia or glaucoma.

Adverse effects. Dry mouth, blurred vision, photophobia, constipation, urinary retention, tachycardia, flushing, hyperthermia, confusion, delirium and memory impairment. Long-term anticholinergic burden is associated with cognitive decline.

Toxidrome. Hot, dry, flushed skin, dilated pupils, tachycardia, urinary retention, absent bowel sounds, agitation and delirium, with seizures and arrhythmia in severe cases. Management is cooling, benzodiazepines for agitation, and supportive care. Physostigmine 0.5 to 2 mg intravenously given slowly is used for severe delirium or tachycardia when tricyclic co-ingestion and QRS widening are absent.

Interactions. Additive effect with tricyclic antidepressants, first generation antihistamines, antipsychotics and other anticholinergics. Reduced efficacy of cholinesterase inhibitors and prokinetics. Slow gastric emptying alters absorption of other drugs.

Monitoring. Heart rate, urinary symptoms, bowel function, intraocular pressure risk, cognition and temperature, especially in older adults.

Special groups. Older adults: avoid strongly anticholinergic agents in dementia or delirium risk. Children: high risk of hyperthermia. Down syndrome: increased pupil sensitivity. Renal impairment: reduce trospium to 20 mg once daily at night if creatinine clearance is under 30 mL/min. Breastfeeding: may reduce milk supply. Hot climates: heat illness risk is higher.