Carboanhydrase inhibitors are diuretics that are not used as diuretics or diuretics. The indication for the appointment of these drugs will be glaucoma. Let's take a closer look at the most popular of them.
Acetazolamide (Acetazolamide)
Has diuretic properties. It stops carbonic anhydrase of the proximal renal tubules, reduces the reabsorption of K, Na and water ions (causes an increase in diuresis), leads to a decrease in BCC and metabolic acidosis. Inhibits carbonic anhydrase of the ciliary body and leads to a decrease in intraocular pressure, and also reduces the secretion of aqueous humor, causes antiepileptic activity in the brain. It has good absorption from the gastrointestinal tract, in the blood Cmax after two hours. The action can last up to 12 hours. Reduces IOP by 40-60% and reduces the production of intraocular fluid.
Indications and dosage
Main indications: ophthalmohypertension, glaucoma. In case of glaucoma, 0.125-0.25 g is taken orally 1-3 times a day every other day for 5 days, after which it is necessarytwo-day break.
Side effects: nausea, loss of appetite, diarrhea, allergies, impaired sense of touch, paresthesia, tinnitus, drowsiness. All this can be provoked by inhibitors of carbonic anhydrase. The drugs also have contraindications. These are hypersensitivity (including to sulfonamides), Addison's disease, a tendency to acidosis, acute liver and kidney disease, pregnancy, diabetes mellitus, uremia..
Drug: Polish-produced Polpharma "Diakarb" tablets, 0.5 g each.
Dorzolamide (dorzolamide)
Inhibits isoenzyme II carbonic anhydrase activity (starts the reversible hydration reaction of carbon dioxide and carbonic acid dehydration) of the ciliary eye body. The secretion of intraocular moisture decreases by 50%, the formation of bicarbonate ions slows down, and the transport of water and sodium is partially reduced. The production of intraocular fluid decreases by 38%, which does not affect the outflow.
Penetrates into the eyeball mainly through the limbus, sclera or cornea. Partially absorbed into the vascular system from the mucous membrane of the eye (probably the occurrence of diuretic and other effects characteristic of sulfonamides). After the substance has entered the blood, it quickly penetrates into erythrocytes, which contain a large amount of carbonic anhydrase II. Dorzolamide is 33% bound to plasma proteins. It shows the maximum hypotensive effect after instillation after 2 hours and retains it for 12 hours. Atinstillation up to 2 times a day reduces intraocular pressure by 9-21%, and when instilled 3 times a day - by 14-24%. The decrease in intraocular pressure when using a 2% solution can reach a maximum of 4.5-6.1 millimeters of mercury. A 3% solution will be less effective because it will be washed out of the conjunctival cavity faster, as it causes severe lacrimation. In combination with the appointment of timolol, it has an additional pronounced effect from 13 to 21%. Carbonic anhydrase inhibitors have a minimal effect on blood pressure and heart rate. Diuretics of this group are not used for their intended purpose. More on that later.
Indications and dosage
Indications: primary and secondary open-angle glaucoma, ophthalmohypertension. The drug is indicated 1 drop 2-3 times a day. Side effects: paresthesia, weight loss, depression, skin rashes, aplastic anemia, agranulocytosis, fatigue, headache, toxic epidermal necrolysis, bitterness in the mouth, nausea, increase in the thickness of the cornea, iridocyclitis, blepharitis, keratitis, conjunctivitis, photophobia, blurred vision, itching and tingling in the eyes, discomfort, Stevens-Johnson syndrome, burning, lacrimation.
This carbonic anhydrase inhibitor (eye drops) has the following contraindications: hypersensitivity (including sulfonamides), childhood, acute liver and kidney disease, pregnancy and breastfeeding. Drug: eye drops"Trusopt", containing 20 mg of dorzolamide hydrochloride in 1 ml of a solution. Bottle capacity - 5 ml. Manufactured in the Netherlands by Merck Sharp & Dohme.
Carboanhydrase inhibitors: Brinzolamide (brinzolamide)
The newest carbonic anhydrase blocker that has the ability, when applied topically, to significantly reduce and control IOP. Brinzolamide has a high selectivity for carbonic anhydrase II and the most suitable physical properties to penetrate effectively into the eye. When compared with dorzolamide and acetozolamide, it was found that brinzolamide is the most potent substance in the carbonic anhydrase inhibitor group. There is evidence that local or intravenous application of brinzolamide leads to an improvement in the ONH. It also lowers IOP by an average of 20%. Not all carbonic anhydrase inhibitors work this way. Brinzolamide has a unique mechanism of action.
Indications and dosages
Indications for use: ophthalmohypertension, open-angle glaucoma. Used 2 times a day, drop by drop.
Side effects: taste perversion, foreign body sensation, blurred vision after instillation (temporary) and burning sensation. Better locally tolerated than dorzolamide. Contraindications: hypersensitivity to the components of the drug (including sulfonamides), childhood, pregnancy and breastfeeding.
Drug: Azopt eye drops containing 10 mg of brinzolamide in 1 ml of suspension. Capacityvial is 5 ml. Manufactured in the USA by Alcon.
What other carbonic anhydrase inhibitors are there?
Prostaglandin derivatives
Latanoprost (latanoprost) is a selective prostaglandin receptor agonist. Increases the outflow of intraocular fluid through the choroid of the eyeball, which leads to a decrease in intraocular pressure. Does not affect the production of aqueous humor. May change pupil size, but only slightly. When instilled, it penetrates in the form of isopropyl ether through the cornea and is hydrolyzed there to the state of a biologically active acid, which can be determined in the first 4 hours in intraocular fluid and in plasma during the first hour. 0.16l/kg – volume of distribution. Two hours after attachment, the highest concentration of the substance in the aqueous humor is reached, after which it is distributed first in the anterior segment, that is, the eyelids and conjunctiva, and then enters the posterior segment (in a small amount). The active form in the tissues of the eye is practically not metabolized, mainly biotransformation occurs in the liver. Metabolites are predominantly excreted in the urine. Consider some more carbonic anhydrase inhibitors.
Unoprostone
Isopropyl unoprostone is a docosanoid derivative that rapidly lowers intraocular pressure (IOP) through a novel pharmacological mechanism. Without changing the time of intraocular fluid production, it facilitates its outflow. Studies have shown that compared to 0.5% maleatetimolol, isopropyl unoprostone has a similar or even higher activity in relation to lowering IOP. The drug does not affect accommodation and does not cause a decrease in blood flow in the eye tissues, miosis or mydriasis; delay in corneal regeneration was also not detected. After topical application, unchanged isotropil unoprostone was not detected in plasma.
Carboanhydrase inhibitors for glaucoma should only be prescribed by a doctor, self-medication is unacceptable.
