Chapter 7: Cholinergic Receptor Antagonists

Cholinergic Receptor Antagonists agents function by inhibiting parasympathetic nerve stimulation, resulting in clinical effects such as tachycardia, bronchodilation, reduced exocrine secretions, and smooth muscle relaxation in the gastrointestinal and urinary tracts. The pharmacokinetics of these drugs are explored, noting that tertiary amines like atropine can cross the blood-brain barrier to cause central nervous system effects ranging from sedation to delirium, whereas quaternary amines like ipratropium and tiotropium are poorly absorbed systemically and are therefore ideal for localized treatment of obstructive lung diseases like asthma and COPD. Significant attention is given to the therapeutic applications of antimuscarinics, including the use of tropicamide for ocular mydriasis and cycloplegia, dicyclomine for irritable bowel syndrome, and uroselective blockers like solifenacin and oxybutynin for managing overactive bladder and incontinence. The chapter also outlines the dose-dependent toxicity of atropine, characterized by the mnemonic describing dry skin, hyperthermia, blurred vision, and confusion, alongside the use of the cholinesterase inhibitor physostigmine as an antidote. The discussion then shifts to nicotinic receptor antagonists, specifically the neuromuscular blocking agents used in anesthesia. These are categorized into nondepolarizing (curariform) agents, such as rocuronium, vecuronium, and cisatracurium, and the single depolarizing agent, succinylcholine. The mechanism of nondepolarizing blockers involves competitive antagonism at the skeletal muscle motor end plate, a blockade that can be reversed by cholinesterase inhibitors like neostigmine or the selective encapsulating agent sugammadex. In contrast, succinylcholine mimics acetylcholine to cause persistent depolarization and fasciculations followed by paralysis, making it useful for rapid sequence intubation despite risks like hyperkalemia and malignant hyperthermia. Special consideration is given to the unique elimination pathways of these paralytics, such as the Hofmann degradation of cisatracurium, which is advantageous in patients with organ failure.