Treatment is aimed at reduction of IOP to minimize continued optic nerve head damage. the washout effect from instilling multiple drops, and a potential reduction in the side effects related to multiple doses of preservatives. strong class=”kwd-title” Keywords: brinzolamide, timolol, glaucoma, fixed combination therapy, ocular hypertension Introduction Glaucoma is the second leading cause of blindness in the world. It is estimated that approximately 60.5 million people suffer from glaucoma. In the United States, it is estimated that almost three million people VP3.15 have open-angle glaucoma. By the year 2020, it is predicted that 11.1 million people will be bilaterally VP3.15 blind from glaucoma worldwide.1 Glaucoma is a characteristic optic neuropathy for which the only known modifiable risk factor is intraocular pressure (IOP). Other risk factors for progression of open-angle glaucoma, cannot currently be altered. Therefore, therapeutic options focus on controlling the pressure inside the eye. As with the management of any chronic, asymptomatic disease, challenges exist for both the patient and the physician. Treatment for glaucoma is generally chronic and may last decades. Even after surgical intervention, further IOP-lowering may be VP3.15 required. Patients most often do not notice small or moderate loss of peripheral vision as occurs early in the course of the disease, so as with other asymptomatic diseases, convincing patients that medications are crucial to preserving their vision can be difficult. Long-term use of eye drops reduces patient quality of life, VP3.15 and the more drops required, the greater the difficulty with and reported worsening of compliance.2 Balancing quality of life with the need for medications can be difficult, and any decrease in the number of drops may improve that balance. Medications may be costly, troublesome to administer, and can cause side effects which range from irritating to dangerous. In choosing a drug regimen, the patient and RICTOR physician must decide which treatment is most acceptable to both parties. Major classes of medications include beta-blockers, alpha-adrenergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. As more drug classes have become available, fixed combinations of these classes are being formulated. The fixed combination therapies currently available in the United States include dorzolamide-timolol (Cosopt?, Merck Inc, Whitehouse Station, NJ) and brimonidine-timolol (Combigan?, Allergan Inc, Irvine, CA). In Europe, fixed combinations of latanoprost-timolol (Xalacom?, Pharmacia Inc, New York, NY), travoprost-timolol (Duotrav?, Alcon Inc, Fort Worth, TX), bimatoprost-timolol (Ganfort?, Allergan Inc) and brinzolamide-timolol (Azarga?, Alcon Inc) are also available. Combination drugs may provide benefits of improved patient adherence and potential of reduced cost. This article will focus on the fixed combination of brinzolamide-timolol. Pharmacology There are no published data on the pharmacokinetics of the brinzolamide-timolol fixed-dose combination, but the pharmacokinetics of each individual drug are known. Brinzolamide is a highly specific and reversible carbonic anhydrase inhibitor. It targets carbonic anhydrase II, the predominant isoenzyme in the ciliary processes. Carbonic anhydrase II is also found in many other tissues of the body, including the corneal endothelium. The formation of bicarbonate ions is blocked by brinzolamide. This prevents sodium transport through the ciliary epithelium and results in decrease of aqueous humor formation.3 Timolol is a nonselective beta-adrenergic (beta-1 and beta-2) receptor antagonist that blocks beta-adrenergic receptors in the ciliary body, which leads to a reduction of cyclic AMP-dependent aqueous humor formation. Beta antagonists were traditionally first-line treatment for IOP, but in recent years the prostaglandin analogs have generally replaced them as first-line therapy.4 Following ocular administration, systemic absorption of both medications does occur. VP3.15 The systemic effects of brinzolamide and timolol are discussed in the Safety section of this article. With the issues surrounding patient compliance and tolerability of treatment, new and more efficacious modes of drug delivery are needed. Contact lenses have been developed with high loading and controllable sustained release of medication and are.
