Topical Ophthalmic β‐Adrenergic Blockade for the Treatment of Glaucoma and Ocular Hypertension

Abstract

Since the late 1970s, topical beta-adrenergic blockers have been the drugs of choice in treating ocular hypertension and associated glaucoma. The currently available drugs are timolol, betaxolol, levobunolol, metipranolol, and carteolol. All reduce intraocular pressure by decreasing the production of aqueous humor. Although these drugs are applied locally in the eye, they may enter the general circulation and reach concentrations high enough to cause systemic effects, including alterations in heart rate and rhythm, bronchoconstriction, dyslipidemia, and central nervous system abnormalities. Interactions with other drugs may also occur. Ocular beta- blockers differ in beta 1-selectivity (betaxolol is beta 1-selective, whereas the other drugs are nonselective) and in intrinsic sympathomimetic activity (ISA) or partial agonist properties (only carteolol possesses ISA). These differences give betaxolol and carteolol potential advantages in minimizing certain side effects. The advantage of betaxolol vis-à-vis systemic side effects is more clearly established than that of carteolol. Further systematic study is needed to determine what advantages, if any, are conferred by the presence of ISA.

Effect of Betaxolol, Timolol and Nimodipine on Human and Pig Retinal Arterioles

“…The most commonly used class of antiglaucoma agents are the β-adrenergic antagonists which are thought to lower IOP, the greatest risk factor for glaucoma, by reducing the rate of aqueous humor formation, which is under the control of a β-adrenergic mechanism in the ciliary epithelium (Neufeld and Bartels, 1982 ;Brubaker, 1991 ;Collignon-Brach, 1992 ;Frishman, Fuksbrumer and Tannenbaum, 1994). It has long been debated whether these agents also act directly on the retinal circulation to change retinal blood flow.…”

The Effects of a Timolol Maleate Gel-Forming Solution on Normotensive Beagle Dogs

“…68(6): 631-633, 2006 Glaucoma is a painful disease and is characterized by retinal ganglion cell death, optic nerve damage that is usually associated with elevated intraocular pressure (IOP), and progressive loss of vision that could result in blindness. Glaucoma therapy aims to lower IOP in order to preserve ocular function and reduce pain [1].Timolol maleate (TM) is a nonselective beta-adrenergic that substantially reduces the volume of aqueous humor and thereby reduces IOP [1,3,20]. TM ophthalmic solution is widely used to treat glaucoma in humans and dogs.…”

“…Timolol maleate (TM) is a nonselective beta-adrenergic that substantially reduces the volume of aqueous humor and thereby reduces IOP [1,3,20]. TM ophthalmic solution is widely used to treat glaucoma in humans and dogs.…”

Pharmacoydnamics of Beta-Blocker Modulation of Aqueous Humor Production

“…Reduction of aqueous humor production, which can be elicited by topical administration of a variety of beta-adrenergic antagonists (Hurvitz et al, 1991 ;Frishman et al, 1994), is an effective means of reducing IOP. The mechanism underlying the reduction of aqueous humor production by betaadrenergic blockade has yet to be elucidated (Chiou et al, 1985 ;Ross et al, 1979 ;Brubaker et al, 1984 ;Mittag, 1996), although actions on arterioles (Bartels et al, 1980) as well as blockade of beta receptors in the ciliary body (Brubaker et al, 1991 ;Kaufman, 1996) have been proposed.…”