Anticholinergic Drugs: Uses and Side Effects

What Are They?

• M1 - CNS, autonomic ganglia, gastric parietal cells
• M2 - Cardiac (SA node, AV node)
• M3 - Smooth muscle and glands
• Morgan & Mikhail's Clinical Anesthesiology, 7e, p. 431

Common Anticholinergic Drugs

• Morgan & Mikhail's Clinical Anesthesiology, 7e, p. 430-435

Clinical Uses

1. Anesthesia / Premedication

• Antisialagogue: Reduce secretions before intubation or airway procedures (glycopyrrolate preferred; scopolamine most potent)
• Bradycardia reversal: Atropine is the drug of choice for vagal bradyarrhythmias (dose: 0.4-2 mg IV)
• Prevention of reflex bradycardia: oculocardiac reflex, peritoneal traction, baroreceptor reflex

2. Respiratory

• COPD / Asthma: Ipratropium bromide (inhaled) causes bronchodilation by relaxing bronchial smooth muscle; ipratropium (0.5 mg in 2.5 mL) is especially effective in acute COPD when combined with albuterol
• Increased anatomic dead space - exploited therapeutically

3. Overactive Bladder (OAB) / Urology

• Gold standard for OAB treatment - reduce uninhibited detrusor contractions, increase functional bladder capacity
• Approved agents in the US: darifenacin, oxybutynin, solifenacin, tolterodine, trospium
• Useful in neurogenic bladder, incontinence, bladder spasm
• Campbell Walsh Wein Urology, p. 141-142

4. Gastrointestinal

• Reduce GI motility and secretions (used in peptic ulcer disease historically, irritable bowel)
• Pirenzepine (M1-selective) - reduces gastric acid secretion

5. Ophthalmology

• Mydriasis and cycloplegia: used for fundoscopic exam and refraction (cyclopentolate, tropicamide, atropine eye drops)
• Treatment of uveitis (prevent posterior synechiae)

6. Neurology / Psychiatry

• Parkinson's disease: Benztropine and trihexyphenidyl as adjunctive therapy (reduce tremor and rigidity)
• Drug-induced EPS (extrapyramidal symptoms): anticholinergics counteract the EPS caused by antipsychotics
• Motion sickness: Scopolamine (transdermal patch)

7. Toxicology / Emergencies

• Organophosphate / nerve agent poisoning: Atropine (large doses) to counteract excessive cholinergic stimulation

Side Effects

"Dry as a bone, blind as a bat, red as a beet, hot as a hare, mad as a hatter"

• Katzung's Basic and Clinical Pharmacology, 16th Edition, p. 1623

System-by-System Side Effects

• Tachycardia (sinus tachycardia, most common)
• Paradoxical bradycardia at low IV doses of atropine (<0.4 mg)
• Atrial arrhythmias, nodal rhythms
• Atropine flush (cutaneous vasodilation with large doses)

• Drying and thickening of secretions (can worsen mucus plugging)
• Bronchodilation (usually therapeutic, but can increase dead space)

• Excitation, restlessness, hallucinations (stimulation phase)
• Sedation, amnesia (especially with scopolamine)
• Delirium, confusion - "mad as a hatter"
• Toxic psychosis (especially scopolamine patches in elderly and children)
• At high doses: depression, coma, respiratory failure

• Mydriasis (pupillary dilation) - "blind as a bat"
• Cycloplegia (inability to accommodate near vision)
• Risk of precipitating acute angle-closure glaucoma (contraindicated in narrow-angle glaucoma)

• Dry mouth (xerostomia) - most common complaint
• Constipation
• Decreased GI motility, prolonged gastric emptying
• Reduced lower esophageal sphincter pressure

• Urinary retention - especially dangerous in elderly men with benign prostatic hyperplasia (BPH)

• Hyperthermia ("atropine fever") - from impaired sweating
• Decreased sweating - "dry as a bone"

• Flushing - "red as a beet"
• Dry skin (anhidrosis)
• Local reactions with transdermal patches (skin erythema, pruritus)

Special Considerations

Glycopyrrolate vs. Atropine

Oxybutynin and Cognition

• Campbell Walsh Wein Urology, p. 146-148

Vulnerable Populations

• Elderly: Much more susceptible to urinary retention, constipation, delirium, falls
• Children: Especially sensitive to toxic effects; cases reported from ophthalmic drops absorbed systemically
• BPH patients: High risk of urinary retention

Anticholinergic Toxidrome and Antidote

• Symptoms: Dilated pupils, hyperthermia, dry flushed skin, tachycardia, urinary retention, delirium/coma
• Antidote: Physostigmine (cholinesterase inhibitor that crosses BBB) - 0.5-1 mg IV slowly; reverses both peripheral and central effects
• Benzodiazepines for agitation/seizures
• Do NOT use physostigmine in tricyclic antidepressant overdose - can precipitate heart block or asystole
• Katzung's Basic and Clinical Pharmacology, 16th Edition, p. 1623-1624

Summary Table of Side Effects by Mnemonic