Carbonic anhydrase inhibitors are diuretics that are not used as diuretics or diuretics. Indication for the appointment of these drugs is glaucoma. Consider in more detail the most popular of them.
Acetazolamide (Acetazolamide)
Has diuretic properties. It stops carbonic anhydrase of the proximal renal tubules, reduces the reverse absorption of K, Na and water ions (causes an increase in diuresis), leads to a decrease in bcc and metabolic acidosis. It inhibits the carbonic anhydrase of the ciliary body and leads to a decrease in intraocular pressure, and also reduces the secretion of aqueous humor, and causes antiepileptic activity in the brain. It has good absorption from the digestive tract, in the blood Cmax after two hours. The action can last up to 12 hours. It reduces IOP by 40-60% and reduces the production of intraocular fluid.
Indications and dosage
The main indications: ophthalmic hypertension, glaucoma. With glaucoma, they take 0.125-0.25 g 1-3 times a day every other day for 5 days, after which a two-day break is needed.
Side effects: nausea, loss of appetite, diarrhea, allergies, impaired touch, paresthesia, tinnitus, drowsiness. All this can trigger carbonic anhydrase inhibitors. Drugs also have contraindications. This is excessive sensitivity (including sulfonamides), Addison's disease, a tendency to acidosis, acute liver and kidney disease, pregnancy, diabetes mellitus, uremia.
Restrictions on the use: pulmonary embolism, emphysema (possibly increased acidosis).
Preparation: Polish-made tablets of Polpharma Diacarb, 0.5 g each
Dorzolamide (dorzolamide)
Inhibits isoenzyme II carbonic anhydrase activity (triggers a reversible hydration reaction of carbon dioxide and carbonic acid dehydration) of the ciliary eye body. The secretion of intraocular moisture is reduced by 50%, the formation of ion bicarbonate slows down, and the transport of water and sodium is partially reduced. The production of intraocular fluid is reduced by 38%, which does not affect the outflow.
It penetrates the eyeball mainly through the limb, sclera or cornea. Partially absorbed into the vascular system from the mucous membrane of the eye (the occurrence of diuretic and other effects characteristic of sulfonamides is likely). After the substance has entered the bloodstream, it penetrates rapidly into red blood cells, which contain a large amount of carbonic anhydrase II. At 33%, dorzolamide is associated with plasma proteins. It exhibits the maximum antihypertensive effect after instillation after 2 hours and retains it for 12 hours. When instilled up to 2 times a day by 9-21% it reduces intraocular pressure, and when instilled 3 times a day - by 14-24%. The decrease in intraocular pressure when using a 2% solution can be as high as 4.5-6.1 mmHg. A solution of 3% will be less effective, since it will be more quickly washed out of the conjunctival cavity, as it causes severe lacrimation. In combination with the appointment of timolol has an additional pronounced effect from 13 to 21%. Carboanhydrase inhibitors have a minimal effect on blood pressure and heart rate. Diuretics of this group are not used for their intended purpose. About it further.
Indications and dosage
Indications: primary and secondary open-angle glaucoma, ophthalmic hypertension. The drug is indicated for 1 drop 2-3 times a day.
Side effects: paresthesia, weight loss, depression, skin rashes, aplastic anemia, agranulocytosis, increased fatigue, headache, toxic epidermal necrolysis, bitterness in the mouth, nausea, increased thickness of the cornea, iridocyclitis, blepharitis, keratitis, conjunctivitis, fogging itching and tingling in the eyes, discomfort, Stevens-Johnson syndrome, burning, lacrimation.
This carbonic anhydrase inhibitor (eye drops) has the following contraindications: excessive sensitivity (including sulfonamides), childhood, acute liver and kidney disease, pregnancy and breastfeeding.
Preparation: Trusopt eye drops containing 20 mg of dorzolamide hydrochloride in 1 ml of solution. The capacity of the bottle is 5 ml. Made in the Netherlands by Merck Sharp & Dohme.
Carbonic Anhydrase Inhibitors: Brinzolamide (Brinzolamide)
The latest carbonic anhydrase blocker, with 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 effectively penetrate the inside of the eye. When compared with dorzolamide and acetosolamide, it was revealed that brinzolamide is the most powerful substance in the carbonic anhydrase group of inhibitors. There is evidence that local or intravenous administration of brinzolamide leads to an improvement in optic disc graft. And it reduces the average IOP by 20%. Not all carbonic anhydrase inhibitors work this way. The mechanism of action of brinzolamide is unique.
Indications and dosages
Indications for use: ophthalmic hypertension, open-angle glaucoma. Use 2 times a day drop by drop.
Side effects: taste perversion, foreign body feeling, after instillation blurred vision (temporary) and burning sensation. Locally tolerated better than dorzolamide.
Contraindications: excessive sensitivity to the components of the drug (including sulfonamides), childhood, pregnancy and breastfeeding.
Preparation: Azopt eye drops containing 10 mg of brinzolamide in 1 ml of suspension. The capacity of the bottle is 5 ml. It is made in the USA by the Alcon company.
What other carbonic anhydrase inhibitors are there?
Derivatives of prostaglandins
Latanoprost (latanoprost) is a selective agonist of prostaglandin receptors. It increases the outflow of intraocular fluid through the choroid of the eyeball, which leads to a decrease in intraocular pressure. No effect on the production of aqueous humor. May change pupil size, but slightly. When instilled, it penetrates in the form of isopropyl ether through the cornea and there hydrolyzes to the state of a biologically active acid, which can be determined in the first 4 hours in intraocular fluid and in plasma within the first hour. 0.16l / kg is the volume of distribution. Two hours after joining, the highest concentration of the substance in aqueous humor is achieved, after which it is distributed to begin with in the anterior segment, that is, the eyelids and conjunctiva, and then falls into the posterior segment (in small quantities). The active form in the tissues of the eye is practically not metabolized, mainly biotransformation occurs in the liver. Mostly metabolites are excreted in the urine. Consider some more carbonic anhydrase inhibitors.
Unoprostone
Isopropyl unoprostone is a derivative of docosanoid, which rapidly reduces intraocular pressure (IOP) using the latest pharmacological mechanism. Without changing the time of intraocular fluid production, it facilitates its outflow. Studies have shown that, compared to 0.5% timolol maleate, isopropyl unoprostone has a similar or even higher activity with respect to lower IOP. The drug does not affect accommodation and does not cause a decrease in blood flow in the eye tissues, myosis or mydriasis; a delay in corneal regeneration was also not detected. After topical administration, unchanged isotropyl unoprostone was not detected in plasma.
Inhibitors of carbonic anhydrase in glaucoma should be prescribed only by a doctor, self-medication is unacceptable.