Pharmacological Therapy for Glaucoma

Abstract

For some time the medical treatment of glaucoma has consisted of topical beta-blockers, adrenergic agents, miotics and oral carbonic anhydrase inhibitors (CAIs). However, the therapeutic arsenal available for the medical treatment of glaucoma has recently extended with new classes of ocular hypotensive agents i.e. prostaglandins, local CAIs and alpha2-adrenergic agents. Beta-blockers are still the mainstay in glaucoma treatment and are first line drugs. However, even if they are applied once daily, as with timolol in gel forming solution and levobunolol, the possible cardiopulmonary adverse effects of beta-blockers remain a cause for concern. When monotherapy with beta-blockers is ineffective in reducing intraocular pressure (IOP) or is hampered by adverse effects, a change of monotherapy to prostaglandins, local CAIs, alpha2-adrenergic agonists (brimonidine) or to dipivalyl epinephrine is advised. Prostaglandins, local CAIs and alpha2-adrenergic agonists, such as brimonidine, may in time become first line drugs because they reduce IOP effectively and until now systemic adverse effects have rarely been reported with these agents. The development of a pro-drug of either a local CAI or an alpha2-adrenergic agonist with a sustained and continuous effect on IOP level, which could be applied once a day is suggested. Because of these new developments, miotics, i.e. pilocarpine and carbachol, are recommended as second or third line drugs. The cholinesterase inhibitors are considered third line drugs as better agents with fewer local and systemic adverse effects have become available. Oral CAIs may be used temporarily in patients with elevated IOPs e.g. postsurgery or post-laser, or continuously in patients with glaucoma resistant to other treatment. Combining ocular hypotensive drugs is indicated when the target pressure for an individual patient cannot be reached with monotherapy. Combination therapy of beta-blockers is additive with prostaglandins, topical CAIs and miotics. Prostaglandins such as latanoprost can be combined with beta-blockers, adrenergic agents, local CAIs and miotics. Combinations with brimonidine or local CAIs need further investigation. Treatment of glaucoma with the new ocular hypotensive agents, either in monotherapy or combination therapy, may provide lower IOPs and delay or postpone the need for surgery.

Comparison of Travoprost and Bimatoprost plus Timolol Fixed Combinations in Open-Angle Glaucoma Patients Previously Treated with Latanoprost plus Timolol Fixed Combination

“…The use of combination therapy frequently is necessary at any stage of the disease, 8,9 as it has been reported in the Ocular Hypertension Treatment Study 9 and in the Collaborative Initial Glaucoma Treatment Study, 10 where up to 50% and 75% of patients, respectively, required 2 or more drugs to reach their target pressure. When 2 drugs are required to control the IOP, there are a number of potential advantages in using a fixed combination rather than separate drugs, including no risk of drug washout, 11 reduced exposure to preservatives, and ultimately better patient compliance and quality of life.…”

Novel drug delivery systems for glaucoma

“…24 It reduces IOP by increasing the outflow of the aqueous. As a drop, it requires four doses a day to maintain a reduced IOP.…”

“…With the advent of other medications in the late 1970's and 1980's, pilocarpine use has declined steadily and is currently utilized after others have been tried. 24 However, it was one of the first drugs used in a sustained release implant in the 1970's to circumvent the need for repeated daily dosing and reduce the side effects as the Ocusert implant, described further below.…”

“…Several studies indicate that both the IOP-lowering medications and potential neuroprotective agents have a low enough effective concentration to be suitable for sustained delivery. 24 Second, one must consider the drug's stability and its interaction with, what is most likely, a hydrophobic polymer environment. Stronger association between a drug and polymer increases the likelihood for long-term, sustained delivery.…”

Pharmacogenetics of Ophthalmic Topical β-Blockers

“…They are prescribed for the treatment of a number of vascular (e.g., coronary artery disease) and nonvascular (e.g., glaucoma) diseases. In the treatment of glaucoma, when applied topically, nonselective β-blockers, such as timolol maleate, reduce IOP by 27-35% [19]. β-blockers reduce IOP by inhibition of aqueous humor production [20] and not by increasing aqueous humor outflow [21,22].…”