Glycopyrrolate - Drug Monograph

Introduction

Glycopyrrolate is an anticholinergic medication that belongs to the class of quaternary ammonium compounds. It is a synthetic antimuscarinic agent that inhibits the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the central nervous system. First approved by the FDA in 1961, glycopyrrolate has established itself as an important therapeutic agent in various clinical settings due to its potent antisecretory properties and limited central nervous system penetration.

Mechanism of Action

Glycopyrrolate competitively inhibits the action of acetylcholine at muscarinic receptors, particularly M1, M2, and M3 subtypes. As a quaternary ammonium compound, it carries a permanent positive charge, which limits its ability to cross the blood-brain barrier and results in minimal central nervous system effects. The drug reduces secretions from salivary, bronchial, sweat, and gastric glands, and decreases gastrointestinal motility. It also produces mydriasis and cycloplegia when applied topically to the eye.

Indications

• Preoperative medication: Reduction of salivary, tracheobronchial, and pharyngeal secretions
• Intraoperative administration: Counteraction of intraoperative bradycardia and hypotension caused by vagal stimulation
• Peptic ulcer disease: Adjunctive therapy for reducing gastric acid secretion
• Chronic drooling: Management of pathological hypersalivation in neurological conditions
• Hyperhidrosis: Control of severe sweating
• Off-label uses: Treatment of asthma, COPD, and as a reversal agent for neuromuscular blockade

Dosage and Administration

• Preoperative: 0.004 mg/kg IM 30-60 minutes before anesthesia
• Intraoperative: 0.1 mg IV as needed for bradycardia
• Peptic ulcer: 1-2 mg PO 2-3 times daily

• Preoperative: 0.004-0.008 mg/kg IM (maximum 0.1 mg)
• Chronic drooling: 0.02-0.1 mg/kg PO 2-3 times daily (maximum 6 mg/day)

• Renal impairment: Dose reduction required (CrCl <30 mL/min)
• Hepatic impairment: Use with caution
• Geriatric: Start with lower doses due to increased sensitivity

Pharmacokinetics

• Absorption: Poor oral bioavailability (10-25%) due to quaternary ammonium structure
• Distribution: Limited tissue penetration; does not cross blood-brain barrier effectively
• Metabolism: Minimal hepatic metabolism
• Elimination: Primarily renal excretion (80-90% unchanged); elimination half-life 0.5-1.2 hours
• Protein binding: Minimal protein binding

Contraindications

• Hypersensitivity to glycopyrrolate or other anticholinergics
• Glaucoma (particularly narrow-angle)
• Obstructive uropathy
• Obstructive gastrointestinal disorders
• Severe ulcerative colitis
• Myasthenia gravis
• Acute hemorrhage with cardiovascular instability
• Toxic megacolon complicating ulcerative colitis

Warnings and Precautions

• Cardiovascular effects: May cause tachycardia; use with caution in patients with cardiac disease
• Heat prostration: Risk of heat stroke in hot environments due to decreased sweating
• Mental status changes: Although CNS penetration is limited, elderly patients may experience confusion
• Gastrointestinal disorders: May precipitate paralytic ileus
• Renal impairment: Requires dose adjustment due to renal elimination
• Pregnancy: Category B - use only if clearly needed
• Lactation: Excreted in breast milk; use with caution

Drug Interactions

• Other anticholinergics: Additive effects (antihistamines, tricyclic antidepressants)
• Ketoconazole: Reduced absorption of ketoconazole
• Metoclopramide: Antagonizes gastrointestinal effects
• Digoxin: Increased serum digoxin levels possible
• Potassium chloride: Increased risk of GI mucosal lesions
• CNS depressants: Enhanced sedative effects

Adverse Effects

• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Tachycardia
• Drowsiness

• Anaphylaxis
• Angioedema
• Paralytic ileus
• Acute urinary retention
• Hyperthermia
• Psychiatric disturbances

Monitoring Parameters

• Heart rate and rhythm
• Blood pressure
• Urinary output
• Bowel sounds and function
• Intraocular pressure in patients at risk for glaucoma
• Mental status, particularly in elderly patients
• Electrolytes and renal function with long-term use

Patient Education

• Take exactly as prescribed; do not exceed recommended dosage
• May cause drowsiness or blurred vision - avoid driving or operating machinery
• Maintain adequate hydration, especially in hot weather
• Use sugar-free candies or gum to relieve dry mouth
• Report immediately: difficulty urinating, eye pain, palpitations, or severe constipation
• Inform all healthcare providers about glycopyrrolate use
• Store at room temperature away from moisture and heat

References

1. American Society of Health-System Pharmacists. AHFS Drug Information. Glycopyrrolate monograph. 2023. 2. Lexicomp Online. Glycopyrrolate: Drug information. UpToDate; 2023. 3. Pharmaceuticals M. Robinul (glycopyrrolate) prescribing information. 2022. 4. Das S, Kumar P, Kiran U, et al. Glycopyrrolate: its current status as a perioperative medication. Anesth Essays Res. 2017;11(2):297-302. 5. Mato A, Limeres J, Tomás I, et al. Management of drooling in disabled patients with scopolamine patches. Br J Clin Pharmacol. 2010;69(6):684-688. 6. FDA Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations.