Pigmentary Glaucoma Medication
- Author: Yaniv Barkana, MD; Chief Editor: Hampton Roy, Sr, MD more...
Despite the fact that glaucoma is not simply a disease of elevated intraocular pressure (IOP), current medical therapy is directed toward lowering IOP.
A rational approach to choosing antiglaucoma medication should minimize the number of medications and probability of significant adverse effects.
As mechanisms of axonal death by apoptosis become better understood, therapies may be developed to protect nerve fibers from ongoing damage and death. This has been termed neuroprotection.
Agents currently under investigation as neuroprotective include the following: glutamate receptor blockers, calcium channel blockers, inhibitors of nitric oxide synthase, free radical scavengers, and drugs to increase blood flow to the optic nerve.
Bimatoprost (Lumigan), travoprost (Travatan), and unoprostone (Rescula) are new ophthalmic prostaglandin analogs recently approved in the United States. Bimatoprost is a prostamide analog with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Travoprost and unoprostone are prostaglandin F2-alpha (ie, dinoprost) analogs similar to latanoprost. They are selective FP prostanoid receptor agonists believed to reduce IOP by increasing uveoscleral outflow. They are indicated for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension who are intolerant of other IOP-lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another IOP-lowering medication.
Bimatoprost and travoprost are each administered once daily at bedtime (ie, 1 gtt in affected eye[s] hs); whereas, unoprostone must be administered bid. They have not been studied in pediatric patients.
These medications are contraindicated if hypersensitivity has been documented. No drug interactions have been reported. All are classified as pregnancy category C (ie, safety for use during pregnancy has not been established).
Like latanoprost, all demonstrate the unusual adverse effect of permanent increase in pigment of the iris (ie, increases brown pigment) and eyelid, and they may increase eyelash growth. Bacterial keratitis may occur. Use is cautioned in uveitis or macular edema. They should not be used if inflammation is present.
Topical adrenergic agonists (sympathomimetics) decrease aqueous humor secretion.
Selective alpha2-receptor antagonist that reduces aqueous humor formation and possibly increases uveoscleral outflow.
Apraclonidine 0.5%, 1% (Iopidine)
Reduces IOP whether or not accompanied by glaucoma. Selective alpha-adrenergic agonist without significant local anesthetic activity. Has minimal cardiovascular effect.
Topical beta-adrenergic receptor antagonists decrease aqueous humor production by the ciliary body. Adverse effects are due to systemic absorption of drug (decreased cardiac output and bronchoconstriction). In susceptible patients, this may cause bronchospasm, bradycardia, heart block, or hypotension. Monitor patient's pulse rate and blood pressure; patients may be instructed to perform punctal occlusion after administering the drops. Depression or anxiety may be experienced in some patients, and sexual dysfunction may be initiated or exacerbated.
Levobunolol (Betagan) 0.25%, 0.5%
Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production.
May reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor or by outflow.
Betaxolol ophthalmic (Betoptic)
Beta1-selective adrenergic antagonist. Selectively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors. Reduces IOP by reducing production of aqueous humor.
Blocks beta1-receptors and beta2-receptors and has mild intrinsic sympathomimetic effects.
Beta-adrenergic blocker that has little or no intrinsic sympathomimetic effects and membrane stabilizing activity. Has little local anesthetic activity. Reduces IOP by reducing production of aqueous humor.
Nonselective beta-blocker. May reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor.
Sympathomimetics (epinephrine and dipivefrin)
These agents increase the outflow of aqueous humor through trabecular meshwork and possibly through uveoscleral outflow pathway, probably by a beta2-agonist action. As many as one third of patients do not respond to these drugs.
Lower IOP by increasing outflow and reducing production of aqueous humor. Used as adjunct to miotic or beta-blocker therapy. Combination of miotic and sympathomimetic will have additive effects in lowering IOP.
Dipivefrin (AKPro, Propine)
Prodrug of epinephrine, designed to lower incidence of adverse effects.
Carbonic anhydrase inhibitors
Reduce secretion of aqueous humor by inhibiting carbonic anhydrase (CA) in the ciliary body. In acute angle-closure glaucoma, administer systemically; apply topically in patients with open-angle glaucoma. These drugs are less effective, and their duration of action is shorter than many other classes of drugs. Adverse effects are relatively rare but include superficial punctate keratitis, acidosis, paresthesias, nausea, depression, and lassitude.
Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than 1 ophthalmic drug is being used, administer the drugs at least 10 min apart. Reversibly inhibits CA, reducing hydrogen ion secretion at renal tubule, and increases renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor.
Catalyzes reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. May use concomitantly with other topical ophthalmic drug products to lower IOP. If more than 1 topical ophthalmic drug is being used, administer drugs at least 10 min apart.
CA inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably slows bicarbonate ion formation with subsequent reduction in sodium and fluid transport.
Timolol is a nonselective beta-adrenergic receptor blocker that decreases IOP by decreasing aqueous humor secretion. Both agents administered together bid may result in additional IOP reduction compared with either component administered alone, but reduction is not as much as when dorzolamide tid and timolol bid are administered concomitantly.
Miotic agents (parasympathomimetics)
These drugs contract the ciliary muscle, tightening trabecular meshwork and allowing increased outflow of aqueous. Miosis results from action of these drugs on the pupillary sphincter. Adverse effects include brow ache, induced myopia, and decreased vision in low light.
Also available as Pilogel, a naturally occurring alkaloid, pilocarpine mimics muscarinic effects of acetylcholine at postganglionic parasympathetic nerves. Stimulates salivary glands and smooth muscle, decreasing aqueous production and increasing outflow.
Prostaglandin analogs increase uveoscleral outflow of aqueous. One mechanism of action may be through the induction of metalloproteinases in the ciliary body, which breaks down the extracellular matrix, reducing resistance to outflow through the ciliary body. They can be used in conjunction with beta-blockers, alpha-agonists, or topical CA inhibitors. Many patients respond well to these agents; others do not respond at all. Adverse effects include iris pigmentation, cystoid macular edema, and uveitis.
May decrease IOP by increasing outflow of aqueous humor.
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