Brinzolamide is a carbonic anhydrase inhibitor (CAI) used to lower intraocular pressure (IOP) in patients with open-angle glaucoma (POAG) or ocular hypertension (OH).
Brinzolamide is commonly available as a 1% suspension. It can be used in patients unresponsive to beta-blockers or in whom beta-blockers are contraindicated.
Pharmacodynamics:
Pharmacologically, brinzolamide is a highly specific, non-competitive, reversible, and effective inhibitor of carbonic anhydrase II (CA-II). It is able to suppress the formation of aqueous humor in the eye presumably by reducing the rate of formation of bicarbonate ions with subsequent reduction in sodium and fluid transport; and thus, decrease IOP.
Brinzolamide can be added to beta-blockers and prostaglandins. In the latter combination, prostaglandin derivatives improve the uveoscleral outflow but also increase the activity of CA in ciliary epithelium which may lead to a secondary increase in aqueous humor secretion. This may slightly reduce the efficacy of prostaglandin analogues. Topical CAIs inhibit CA-II, thus overcoming the increased ciliary body activity of prostaglandin analogues, and indirectly improving prostaglandin efficacy.
Brinzolamide could have a secondary possible effect on ocular flow too. Some clinical studies have shown a mild improvement of ocular blood flow.
Pharmacokinetics:
The recommended frequency for topical application is two to three times per day. As monotherapy in patients with POAG or OH, brinzolamide 1% demonstrated IOP-lowering efficacy that was significantly greater than placebo, equivalent to three-times-daily dorzolamide 2% but significantly lower than twice-daily timolol 0.5%.
Phase III trials have reported that brinzolamide 1% twice- and thrice-daily produced statistically significant IOP reductions from baseline, and that both treatments were clinically equivalent to one another.
Both regimens produce diurnal mean IOP reductions from baseline in the range of 13.2-21.8%.
Side effects:
In clinical trials, brinzolamide 1% was well tolerated causing only non-serious adverse effects that were generally local, transient and mild to moderate in severity. The incidence of the most common adverse events associated with the use of brinzolamide 1% was either similar to (blurred vision and abnormal taste) or significantly lower than (ocular discomfort) with dorzolamide 2%.
Common, but mild side effects: blurred vision; bitter, sour, or unusual taste; itching, pain, watering, or dryness of the eyes; feeling that something is in the eye; headache; runny nose
Rare, but serious: fast or irregular heartbeat; fainting; skin rash, hives, or itching; severe eye irritation, redness, or swelling; swelling in the face, lips, or throat; wheezing or trouble breathing
Precautions:
- Hypersensitivity to other sulfonamides
- Acute angle-closure glaucoma
- Concomitant administration of oral carbonic anhydrase inhibitors
- Moderate-to-severe chronic kidney disease or liver disease.
Corneal decompensation:
In the corneal endothelium, CA-II plays a role in the pumping mechanism, which helps to maintain the relatively dehydrated state of the corneal stroma. Inhibition of this mechanism can cause corneal decompensation and edema, which leads to impaired vision.
In a randomized, double-blind clinical trial, 372 glaucomatous and OH patients received brinzolamide 1% or timolol 0.5%. After 18 months of treatment, no significant change was found in corneal thickness and corneal endothelium cell density. However, in this study only subjects with healthy corneas were included. Some concern remained in patients with compromised corneas, because in 2 published case reports corneal decompensation has been described in patients with keratopathy after treatment with dorzolamide.
ALSO SEE= "FIXED DRUG COMBINATIONS":
https://ourgsc.blogspot.com/2019/10/fixed-drug-combinations-in-glaucoma.html
