5.20 : Cholinergic Antagonists: Pharmacokinetics

Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations, while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and the conjunctiva. However, when inhaled, quaternary antimuscarinics are less lipid soluble and have limited systemic absorption.

Antimuscarinics are distributed throughout the body, with tertiary antimuscarinics penetrating the blood-brain barrier, while quaternary compounds are excluded from the brain. Antimuscarinics undergo hepatic metabolism, and elimination with atropine rapidly metabolizing in the liver and excreted unchanged in the urine. Most swallowed ipratropium and tiotropium are excreted via feces. Elimination of quaternary compounds is generally slower.

Based on their duration of action, antimuscarinics are categorized as either short-acting antimuscarinics (e.g., ipratropium) or long-acting (e.g., glycopyrrolate, tiotropium, and aclidinium). Antimuscarinics also interact with other drug classes, including tricyclic antidepressants, antihistamines, antianxiety and antipsychotic agents, which can exacerbate antimuscarinic side effects. Antacids can increase the stomach pH and form complexes with antimuscarinics, reducing their absorption.