Bethanechol

Bethanechol is a synthetic choline ester that acts as a selective muscarinic agonist with minimal nicotinic effect and resistance to cholinesterase hydrolysis. It contracts the bladder detrusor and increases gut tone and motility. Its main use is postoperative or postpartum nonobstructive urinary retention and neurogenic bladder atony.

Classification. Direct acting cholinergic agonist; carbamic acid ester of beta methylcholine.

Mechanism. Stimulates M3 receptors on detrusor smooth muscle, raising intravesical pressure, and on gut smooth muscle, increasing peristalsis and lower oesophageal sphincter tone.

Pharmacodynamics. Detrusor contraction, increased gastric and intestinal motility, increased secretions, miosis, sweating. Cardiovascular effects are minor after oral dosing.

Pharmacokinetics. Quaternary ammonium compound, so oral absorption is poor and variable and it does not cross the blood brain barrier. Onset 30 to 90 minutes, peak about 1 hour, duration up to 6 hours after large oral doses. Not hydrolysed by cholinesterase; the route of elimination is poorly characterised.

Acute postoperative or postpartum nonobstructive urinary retention and neurogenic atony, adult.

• Starting dose: 5 to 10 mg orally, repeated every hour until satisfactory voiding or a total of 50 mg is reached; this finds the minimum effective dose.

• Maintenance: 10 to 50 mg orally three or four times daily.

• Maximum: 50 mg each dose; 200 mg daily.

• Duration: continue only while retention persists; review at 48 to 72 hours and stop once residual volumes are acceptable.

Children. Safety and dose are not established; use only on specialist advice.

Practice point. Mechanical obstruction, including benign prostatic enlargement and urethral stricture, must be excluded before starting. Catheterisation remains first line for acute retention; bethanechol is an adjunct.

Contraindications. Mechanical obstruction of the bladder neck or gut; recent bladder or bowel surgery or anastomosis; peritonitis; active peptic ulcer; asthma; marked bradycardia or hypotension; coronary artery disease; epilepsy; parkinsonism; hyperthyroidism; vagotonia.

Warnings. In hyperthyroidism it can provoke atrial fibrillation. If the sphincter fails to relax, detrusor contraction against a closed outlet can cause vesicoureteric reflux and upper tract infection.

Adverse effects. Abdominal cramps, diarrhoea, nausea, belching, salivation, sweating, flushing, urinary urgency, headache, blurred vision, bronchospasm, bradycardia and hypotension.

Interactions. Additive cholinergic effects with neostigmine, pyridostigmine and other cholinesterase inhibitors. Ganglion blockers given together can cause a severe fall in blood pressure. Anticholinergic drugs, including tricyclic antidepressants, antihistamines and antipsychotics, oppose its effect.

Special groups.

• Pregnancy: no adequate human data; avoid unless benefit is clear.

• Breastfeeding: no data; abdominal colic and diarrhoea in the infant are possible; prefer catheterisation.

• Older adults: start at 5 mg; watch for orthostatic hypotension and bradycardia.

• Kidney and liver impairment: no specific dose change; start low and titrate.

Overdose and reversal. Cholinergic excess (sweating, salivation, colic, bradycardia, bronchospasm) is reversed with atropine 0.6 to 1.2 mg IV in adults, repeated as needed.

Formulation. Oral tablets, commonly 5, 10, 25 and 50 mg.

Food. Give on an empty stomach, 1 hour before or 2 hours after meals, to reduce nausea and vomiting.

Route. Oral only. Never give intravenously or intramuscularly; parenteral use causes a severe cholinergic reaction with circulatory collapse.

Baseline. Bladder scan or catheter residual volume, pulse, blood pressure, and exclusion of obstruction.

Monitoring. Post void residual after each attempt at voiding; heart rate and blood pressure in the first hours; wheeze in patients with airway disease.

Stopping. Stop if no improvement after several days at maximum tolerated dose, if residual volumes stay high, or if bradycardia or bronchospasm develops.