Parasympathomimetic agents, or miotics, have been used in the treatment of glaucoma for more than 100 years. Traditionally, they are divided into direct-acting cholinergic agonists and indirect-acting anticholinesterase agents.
The direct-acting agent pilocarpine continues to be used in certain circumstances, although it is not commonly prescribed for long-term use. In patients with pigmentary glaucoma, pilocarpine is effective in blunting the IOP spike that can occur with jarring physical activities such as running. This drug is also useful in the management of elevated IOP in aphakic eyes and in patients whose drainage angles are persistently occludable despite laser iridotomy (plateau iris syndrome). It has been associated with poor patient adherence to the treatment regimen because of its adverse effect profile and because of its 3- or 4-times-daily dosing schedule; therefore, it is infrequently used. Lower concentrations and dosing frequencies may be acceptable for management of angles with persistent iridotrabecular contact with a patent peripheral iridotomy.
Indirect-acting agents fell out of favor because of their ocular and systemic adverse effects. They can, however, be very effective and well tolerated in aphakic eyes with glaucoma, but they are rarely used.
Mechanism of Action
Parasympathomimetic agents reduce IOP by causing the longitudinal ciliary muscle fibers that insert into the scleral spur, trabecular meshwork, and inner wall of Schlemm canal to contract, thereby improving outflow facility by causing an unfolding of the trabecular meshwork and widening of the Schlemm canal. Direct-acting agents affect the motor end plates in the same way as acetylcholine, which is transmitted at postganglionic parasympathetic junctions, as well as at other autonomic, somatic, and central synapses. Pilocarpine can reduce IOP by 15%–25%. Indirect-acting agents inhibit the enzyme acetylcholinesterase, thereby prolonging and enhancing the action of naturally secreted acetylcholine.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.