Bethanechol

Mechanism

Mechanism of Action

Synthetic choline ester that acts as a selective agonist of muscarinic cholinergic receptors (M₁, M₂, M₃), with minimal or no activity on nicotinic receptors in the ganglion or neuromuscular plate. It is highly resistant to hydrolysis mediated by the enzyme acetylcholinesterase, which significantly prolongs its duration of action. By selectively binding to M₃ receptors located in the detrusor muscle of the urinary bladder, it activates the α_q subunit of the G protein, stimulating phospholipase C and causing coordinated contraction of the detrusor muscle with concomitant relaxation of the trigone and the internal bladder sphincter. Likewise, it increases peristalsis and contractile tone of the gastrointestinal tract.

Pharmacokinetics

Key Pharmacokinetics

• Routes: Oral. Once administered subcutaneously (a route currently banned due to imminent risk of severe systemic cholinergic crisis); its IM or IV administration is contraindicated.
• Oral absorption: Poor and highly variable. It should always be administered on an empty stomach (1 hour before or 2 hours after meals) to avoid induced postprandial nausea or vomiting.
• Onset of effect: Between 30 to 90 minutes after oral intake.
• Duration: About 1 to 6 hours depending on dose.
• Metabolism: Metabolism in vivo unknown. It is not hydrolyzed by cholinesterase.
• Excretion: Renal in a presumed unchanged form.

Indicators and dose

Approved and Off-label Indications

Approved: Treatment of acute non-obstructive postoperative, postpartum or neurogenic etiology urinary retention (flaccid or hypotonic neurogenic bladder).

Off-label: Refractory severe gastroesophageal reflux to increase basal tonic pressure of the lower esophageal sphincter; moderate xerostomia induced by psychotropic drugs.

Dosage and Adjustments

Urinary Retention (Oral): 10 to 50 mg orally three to four times a day in a scheduled manner. It is advisable to start with a test dose of 5-10 mg to assess tolerance and individual clinical response.

Renal/hepatic adjustment: No dose adjustment guidelines based on specific analytical scales have been described, but close monitoring of excretory function is recommended.

Security

Contraindications

Absolute: Mechanical obstruction of the bladder outlet tract (eg, severe prostatic hyperplasia, urethral stricture) or gastrointestinal tract (pyloric stenosis, fecal impaction); active bronchial asthma or COPD (risk of severe bronchospasm); active peptic ulcer; decompensated hyperthyroidism (can trigger atrial fibrillation); extreme basal bradycardia, active coronary artery disease or severe hypotension.

Relative: Decompensated epilepsy, long-standing Parkinson's disease.

Adverse Effects (ADR)

Common: Deep diaphoresis, sialorrhea (excessive salivation), lacrimation, skin flushing, nausea, diffuse abdominal cramps, urgent diarrhea, bladder frequency, mild headache, pupillary miosis with blurred vision.

Serious: Severe refractory bronchospasm, extreme bradycardia with cardiovascular syncope, acute generalized cholinergic crisis.

Interactions

Anticholinergics (atropine, first generation antihistamines): Direct mutual antagonism of the muscarinic effect.

Acetylcholinesterase inhibitors: Additive additive effect with imminent risk of severe systemic cholinergic toxicity.

Pregnancy and Breastfeeding

FDA Classification: Category C. Its use is discouraged due to the induction of increased uterine tone that can trigger spontaneous abortion or preterm delivery. There is no comprehensive safety data available on its presence in breast milk.