Glycopyrrolate

INDICATIONS:

	Reversal of neuromuscular blockade (NMB), blockade of muscarinic effects of anticholinesterases.
	Anesthesia premedication (vagolysis).
	Reflex-mediated bradycardia.
	Adjunctive treatment of bronchospasm and peptic ulcer disease.

CLASS: Anticholinergic agent.

MODE OF ACTION:

	Semisynthetic quaternary ammonium anticholinergic.
	In contrast to atropine, glycopyrrolate is poorly lipid-soluble, has minimal ability to cross the blood-brain barrier and is devoid of sedative effects.
	Inhibits the action of acetylcholine by reversibly combining with muscarinic cholinergic receptors, reducing pharyngeal, tracheal and bronchial secretions, relaxing bronchial smooth muscle, reducing lower esophageal sphincter tone and raising intraocular pressure.
	Glycopyrrolate decreases gastric hydrogen ion secretion.

ONSET: IV < 1 min (peak 5 min); IM 15-30 min; PO within 50 min (peak 1 h), inhalation 3-5 min (peak 1-2 h).

DURATION: IV 2-3 h vagal blockade, 7 h antisialogogue effect.

CLEARANCE: Half-life 1.25 h (more rapid than atropine); biliary and renal elimination.

ADULT DOSE:

	Reversal of neuromuscular blockade (blocks adverse muscarinic effects): 0.005-0.015 mg/kg IV with neostigmine 0.025-0.07 mg/kg IV, or with 0.1-0.3 mg/kg pyridostigmine IV, administered simultaneously, or 0.2 mg IV for each 1 mg neostigmine and 0.2 mg IV for each 5 mg pyridostigmine.
	Preoperative: 4-6 µg/kg IV/IM/SC or 1 mg PO (injectable solution diluted), 30-60 min before procedure.
	Bronchospasm: 0.4-0.8 mg in NaCl 0.9% 2-3 mL, delivered with nebulizer every 8 h.

PEDIATRIC DOSE:

	Vagal blocking drugs are not routinely given to children preoperatively.
	Atropine is the preferred anticholinergic in children.
	Reversal NMB as adult dose above.
	Respiratory antisecretory: 4-10 µg/kg/dose IM/IV every 4-8 h, maximum 0.2 mg/dose or 0.8 mg/24 h.
	Preoperative IM: < 2 yr 4-8 µg/kg; > 2 yr 4 µg/kg.
	Intraoperative IV: 4 µg/kg, not to exceed 0.1 mg.

NEONATAL DOSE: N/A.

CAUTION: Impaired liver or renal function. Elderly. Asthma. Hyperthyroidism. Coronary artery disease, arrhythmias.

CONTRAINDICATIONS:

	Hypersensitivity to glycopyrrolate.
	Narrow-angle glaucoma.
	Gastrointestinal obstruction, paralytic ileus.
	Benign hypertrophy of prostate or obstructive uropathy.
	Acute GI hemorrhage, ulcerative colitis.

INTERACTIONS:

	Increased risk of anticholinergic effects with concomitant administration of primary anticholinergic drugs and amantidine, antihistamines, antiparkinsonian drugs, clozapine, disopyramide, inhaled ipratropium, haloperidol, orphenadrine, pethidine, phenothiazines, procainamide, quinidine, tricyclic antidepressants.
	Glycopyrrolate may increase the risk of digoxin toxicity by slowing bowel transit.

ADVERSE REACTIONS:

	CNS: headache, confusion, drowsiness, somnolence, dizziness, ataxia.
	Ocular: blurred vision, mydriasis, increased intraocular tension.
	CVS: tachycardia, bradycardia (low dose), orthostatic hypotension, palpitations.
	Pulmonary: dry mouth (xerostomia), dysphagia.
	GIT: nausea, vomiting, 'bloated' feeling, abdominal pain, constipation.
	GU: urinary retention and hesitancy.
	Other: anaphylaxis, anhidrosis, urticaria, fatigue, memory loss.

PREGNANCY: Category B. Unlike atropine, produces no change in fetal heart rate, due to limited placental transfer; this could be detrimental as neostigmine readily crosses the placental barrier.

COMMENTS:

	Glycopyrrolate may be administered before neostigmine if bradycardia is present.
	Glycopyrrolate, as an antisialagogue, is twice as potent as atropine, with a much longer duration and with less tachycardia. Its IV onset is slower compared with atropine.
	In the asthmatic patient, preanesthetic administration of anticholinergic drugs, while causing bronchial smooth muscle relaxation, could theoretically result in inspissation of secretions, leading to airway obstruction.
	Post-NMB effects on the parasympathetic nervous system control of heart rate are shorter for glycopyrrolate than for atropine.
	Small doses of glycopyrrolate, may produce a paradoxical bradycardia (similar to atropine), due to a weak muscarinic cholinergic agonist effect.
	When used as a premedicant, glycopyrrolate has the least effect on pupil diameter compared with other anticholinergics (relevant for glaucoma patients).
	Glycopyrrolate is unlikely to cause central anticholinergic syndrome because of poor penetration of the blood-brain barrier.
	H2 blockers have superceded the use of anticholinergics for gastric acid reduction.