What is glycopyrrolate (glycopyronium)?

Glycopyrrolate (Glycopyrronium): A Comprehensive Overview

Glycopyrrolate is a quaternary ammonium anticholinergic medication that effectively blocks muscarinic receptors with minimal central nervous system effects due to its limited ability to cross the blood-brain barrier, making it particularly valuable for reducing secretions and blocking vagal responses in various clinical settings. 1

Pharmacology and Mechanism of Action

• Glycopyrrolate is a synthetic anticholinergic agent that acts as a competitive antagonist at muscarinic acetylcholine receptors 1
• As a quaternary ammonium compound, glycopyrrolate has limited passage across lipid membranes such as the blood-brain barrier, unlike tertiary amines like atropine and scopolamine 1
• The cardio-vagal blocking action of glycopyrrolate is approximately twice that of atropine, while its inhibition of salivation is 5-6 times greater 2
• Glycopyrrolate has poor oral absorption due to its quaternary nature and does not penetrate placental barriers 2

Clinical Applications

Anesthesia and Perioperative Care

• Used for reduction of secretions and minimization of vagal response, particularly in infants and neonates 3
• Recommended dose for preanesthetic medication: 0.004 mg/kg intramuscularly, given 30-60 minutes before anesthesia induction 1
• Can be administered intravenously during surgery to counteract drug-induced or vagal reflexes and associated arrhythmias at doses of 0.1 mg, repeated as needed at 2-3 minute intervals 1
• Recommended for reversal of neuromuscular blockade at a dose of 0.2 mg for each 1.0 mg of neostigmine 1, 4

Management of Excessive Secretions in Palliative Care

• Effectively reduces excessive secretions associated with dyspnea in palliative care patients 3
• Preferred over other anticholinergics for patients with respiratory congestion at the end of life due to minimal central nervous system effects 5, 6
• Typical dosage for managing respiratory congestion: 0.2-0.4 mg IV every 4 hours as needed or 0.2 mg subcutaneously every 4 hours 6
• Particularly valuable for patients with PPS 20 (end-of-life stage) experiencing respiratory congestion 6

Other Clinical Uses

• Treatment of peptic ulcer disease at a dose of 0.1 mg administered at 4-hour intervals, 3-4 times daily intravenously or intramuscularly 1
• Management of clozapine-induced sialorrhea (excessive salivation) 7
• Used as an adjunct to ketamine anesthesia to attenuate increased upper airway secretions 3
• Available in topical formulations for treatment of hyperhidrosis (excessive sweating) 8

Advantages Over Other Anticholinergics

• Less likely to cause delirium compared to scopolamine or atropine due to minimal central nervous system penetration 3, 5
• Provides more stable hemodynamic effects when used with neostigmine for neuromuscular blockade reversal compared to atropine 4
• Optimal intramuscular dose of 0.2 mg provides effective antisialogogue effects with minimal subjective discomfort 9
• Intravenous administration causes minimal changes in cardiovascular stability 9

Adverse Effects and Precautions

• Common anticholinergic side effects include: xerostomia (dry mouth), urinary hesitancy/retention, blurred vision, mydriasis, tachycardia, decreased sweating, constipation 1
• Less common but serious adverse events include: cardiac arrhythmias, hypertension, hypotension, seizures, respiratory arrest, and allergic reactions 1
• Contains benzyl alcohol, which has been associated with serious adverse events in pediatric patients, particularly neonates and low-birth-weight infants 1
• Elderly patients may be more susceptible to anticholinergic effects and should generally receive lower doses 1
• Post-marketing reports have included cases of heart block and QTc interval prolongation when used with anticholinesterases 1

Clinical Pearls and Considerations

• For management of excessive secretions in palliative care, glycopyrrolate should be started early when congestion is first noted rather than waiting until secretions become severe 6
• Anticholinergics like glycopyrrolate are more effective at preventing new secretion formation than eliminating existing secretions 6
• In nerve agent intoxication, glycopyrrolate can be used to counteract cholinomimetic activity and reduce salivation or bronchial secretions 3
• When used with ketamine, glycopyrrolate can attenuate the increased upper airway secretions that might otherwise lead to severe dyspnea or sense of "suffocation" 3
• For anticholinergic overdose, a quaternary ammonium anticholinesterase such as neostigmine methylsulfate may be given intravenously in increments of 0.25 mg in adults 1

Dosing Considerations

• For preanesthetic medication: 0.004 mg/kg intramuscularly 1
• For intraoperative use: 0.1 mg IV, repeated as needed at 2-3 minute intervals 1
• For neuromuscular blockade reversal: 0.2 mg for each 1.0 mg of neostigmine 1
• For management of excessive secretions in palliative care: 0.2-0.4 mg IV or subcutaneously every 4 hours as needed 6
• For peptic ulcer treatment: 0.1 mg IV or IM every 4 hours, 3-4 times daily 1