Glycopyrrolate

Glycopyrrolate (glycopyrronium bromide) is a synthetic quaternary ammonium antimuscarinic. It does not cross the blood brain barrier, so it dries secretions and blocks vagal effects without sedation or delirium. Main uses are as an antisialagogue, with neostigmine at reversal, for terminal respiratory secretions and for chronic drooling in children with neurological disease.

Classification. Antimuscarinic; quaternary ammonium; peripheral action only.

Mechanism. Competitive antagonist at muscarinic receptors in glands, heart and smooth muscle.

Pharmacodynamics. Potent antisialagogue, about five times atropine on a weight basis, with less tachycardia. IV onset about 1 minute; vagolytic effect 2 to 3 hours; antisialagogue effect up to 7 hours.

Pharmacokinetics. Oral bioavailability about 3%, further reduced by high fat food. IV elimination half life about 1 hour in adults. Excreted mostly unchanged in urine and bile, so it accumulates in kidney impairment.

Antisialagogue before anaesthesia, adult. 4 micrograms/kg IV or IM, usually 200 to 400 micrograms, given IM 30 to 60 minutes before induction or IV at induction. Children: 4 to 8 micrograms/kg IV or IM (maximum 200 micrograms).

Intraoperative vagal bradycardia, adult. 100 to 200 micrograms IV, repeated every 2 to 3 minutes as needed. Children: 4 micrograms/kg IV (maximum 100 micrograms) each dose. Atropine is preferred in unstable bradycardia because of faster peak effect.

With neostigmine for reversal. Glycopyrrolate 0.2 mg for each 1 mg neostigmine IV (equal to 10 to 15 micrograms/kg alongside neostigmine 0.05 mg/kg), mixed in the same syringe or given just before.

Terminal respiratory secretions, adult palliative care.

• 200 micrograms SC every 4 hours as needed.

• Continuous SC infusion 600 to 1200 micrograms over 24 hours.

• Maximum 1.2 mg in 24 hours.

• Start early; established secretions respond less well. Preferred over hyoscine hydrobromide in the conscious patient because it does not sedate.

Chronic severe drooling in children with neurological conditions, 3 to 16 years.

• Oral solution starting at 0.02 mg/kg three times daily.

• Increase by 0.02 mg/kg every 5 to 7 days to response and adverse effects.

• Maximum 0.1 mg/kg three times daily, not exceeding 1.5 to 3 mg each dose depending on weight.

• Review at least every 3 months; reduce if constipation, urinary retention or behavioural change occur.

Peptic ulcer. No longer used.

Contraindications. Angle closure glaucoma; obstructive uropathy; paralytic ileus; severe ulcerative colitis or toxic megacolon; myasthenia gravis (except when reversing cholinesterase inhibitors); unstable cardiac status with tachycardia.

Warnings. Tachyarrhythmia in coronary disease and thyrotoxicosis. Heat stroke from reduced sweating in hot climates. Constipation can progress to faecal impaction, especially in children with cerebral palsy. Oral use in children with severe constipation or urinary retention must stop.

Adverse effects. Dry mouth, constipation, urinary retention, flushing, tachycardia, blurred vision, reduced sweating, nasal congestion, irritability in children.

Interactions. Additive anticholinergic effects with tricyclic antidepressants, antihistamines, antipsychotics and hyoscine. Slower gut transit can raise absorption of digoxin (slow release forms) and delay others. Potassium chloride solid oral forms are contraindicated because slowed transit raises the risk of oesophageal and gut injury.

Special groups.

• Pregnancy: crosses the placenta less than atropine; acceptable for anaesthetic use.

• Breastfeeding: no human data; quaternary structure suggests low transfer; single doses compatible.

• Children: dose by weight; constipation is the dose limiting effect.

• Older adults: lower delirium risk than atropine or hyoscine; still watch for urinary retention.

• Kidney impairment: accumulates. eGFR 30 to 50 mL/min: reduce oral doses and lengthen intervals; eGFR under 30 mL/min: use lowest effective dose and avoid regular dosing where possible. Single anaesthetic doses need no change.

• Liver impairment: no adjustment.

Formulations. Injection 200 micrograms/mL; oral solution 1 mg/5 mL and 320 micrograms/mL (strengths differ by market, a source of error); tablets 1 mg and 2 mg.

Preparation and compatibility. Compatible with neostigmine, 0.9% sodium chloride and glucose 5% for SC infusion. Unstable at pH over 6; do not mix with sodium bicarbonate or thiopental.

Food. Give oral doses 1 hour before or at least 2 hours after meals, avoiding high fat meals.

Monitoring. Heart rate after IV doses. Palliative: secretion score every 4 hours. Paediatric drooling: drooling frequency, bowel habit, urine output, temperature in hot weather, behaviour, at each titration.

Common prescribing errors. Confusing the two oral solution strengths; giving antisialagogue doses to treat unstable bradycardia instead of atropine; continuing oral therapy in a constipated child.