Cholinergics Miotics

Cholinergic agents mimic the actions of the parasympathetic nervous system. One effect of the parasympathetic response is contraction of the iris sphincter, causing the pupil to get smaller (mio-sis). For this reason, the cholinergic drugs are commonly referred to as miotics. All miotics are additive to beta blockers and sympathomimetic agents. They may be direct acting or indirect acting.

The direct-acting agents decrease IOP by increasing the flow of aqueous out of the eye. When the muscarinic receptors in the ciliary body are stimulated, certain fibers of the ciliary body contract. This mechanically opens the drainage system of the trabecular meshwork and increases aqueous outflow. Pilocarpine and carbachol are the 2 direct-acting cholinergics currently available, though less commonly used today.

The indirect-acting cholinergics act in a slightly different way. Also known as anti-cholinesterase drugs, they work by preventing the "clean up" of the neurotransmitter at the receptor site. The neurotransmitter can then remain at the site and have a prolonged effect. Anti-cholinesterase drugs are classified as reversible or irreversible. If the drug is reversible, it has a short action (several hours). Irreversible anticholinesterase drugs have a prolonged action, sometimes lasting up to several days. There are 4 available anticholinesterase therapeutics. Physostig-mine and demercarium bromide are reversible, while echothiophate iodine and isoflurophate are irreversible.

Aside from glaucoma treatment, the miotic drugs are also used in cases of overcorrection (hyperopia) after refractive surgery. The agents most commonly used for this are pilocarpine and echothiophate iodine. Finally, though their miotic property can help to reverse the action of mydri-atic drops, this is not recommended because it may induce an acute angle-closure glaucoma attack.

Ocular side effects are reported frequently with cholinergic therapy. Though true allergic reactions are rare, these agents commonly sting on instillation. They also cause brow ache, headache, accommodative spasm, and induced myopia. These effects are more pronounced in younger patients. While these problems may be substantial when therapy is first instituted, they decrease over time.

The miotic nature of these drugs must be also be taken into account. In patients with cataracts, miosis can markedly decrease vision. Historically, miotics have been said to increase the risk of retinal detachment and cataracts, though this has not been conclusively established. Systemic adverse effects are similar with all cholinergic drugs and include sweating, salivation, stomach and digestive upset, and decreased heart rate. Miotic therapy has proven efficacy and is an inexpensive option. However, with the possible exception of the gel and sustained-release systems (to be discussed shortly), miotic therapy is usually associated with poor compliance—a result of patient discomfort and the frequent administration required (often 4 times a day).


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