5.8 : Direct-Acting Cholinergic Agonists: Pharmacokinetics

Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral administration and unable to cross the blood-brain barrier. In contrast, alkaloids are tertiary amines readily absorbed into the body and can cross the blood-brain barrier. Notably, the quaternary amine-containing alkaloid muscarine is poorly absorbed and induces toxic effects in the central nervous system.

The pharmacokinetics of direct-acting cholinergic drugs play a crucial role in their therapeutic application. Acetylcholine is used as a pharmacological agent during eye surgeries to induce miosis, and it is administered as ophthalmic or eye drops. Similarly, carbachol is topically applied as an eye drop in the treatment of glaucoma. In addition, pilocarpine, another alkaloid, is delivered to the eye through an ocular insert to induce miosis. Bethanechol has limited absorption and is taken orally multiple times daily; it primarily acts on the urinary and gastrointestinal tracts, commonly used for postoperative urinary retention. Renal excretion is the main route of elimination for choline esters and alkaloids. Carbachol, bethanechol, muscarine, and pilocarpine are not hydrolyzed by acetylcholinesterase, and their removal from the body is expedited by acidifying the urine.