Inhibitors of carbonic anhydrase: the mechanism of action of eye drops in glaucoma

Carbonic anhydrase inhibitors refer to diuretics that are not used as diuretics or diuretics. Indications for the appointment of these drugs will be glaucoma. Let's consider in more detail the most popular of them.

Acetazolamide (Acetazolamide)

Has diuretic properties. It stops the carboanhydrase of the proximal renal tubules, reduces the inverse absorption of K, Na and water ions (causes an increase in diuresis), leading to a decrease in bcc and metabolic acidosis. Oppresses the 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. Has a good absorption from the digestive tract, in the blood of Cmax after two hours. The action can last up to 12 hours. At 40-60% reduces IOP and reduces the production of intraocular fluid.

Indications and dosage

The main indications: ophthalmohypertension, glaucoma. When glaucoma inside take 0,125-0,25 g 1-3 times a day every other day for 5 days, after which a two-day break is necessary.

Side effects: nausea, loss of appetite, diarrhea, allergy, impaired touch, paresthesia, tinnitus, drowsiness. All this can provoke inhibitors of carbonic anhydrase. Preparations also have contraindications. This is an excessive sensitivity (to sulfonamides including), Addison's disease, a tendency to acidosis, acute liver and kidney disease, pregnancy, diabetes, uremia.

Restrictions on the use: pulmonary embolism, emphysema of the lung (possibly strengthening acidosis).

Preparation: Polish tablets Polpharma "Diakarb" for 0.5 g.

Dorzolamide (dorzolamide)

Inhibits isoenzyme II carbonic anhydrase activity (Triggers the hydration reaction of reversible carbon dioxide and carbonic acid dehydration) of the eye's ciliary 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. Reduces the production of intraocular fluid by 38%, which does not affect the outflow. Penetrates the eyeball mainly through the limbus, sclera or cornea. Absorbed partially into the vascular systemic channel from the mucous membrane of the eye (probably the emergence of diuretic and other effects inherent in sulfonamides). After the substance has got into the blood, it penetrates quickly into the red blood cells, which contain a large amount of carbonic anhydrase II. By 33% dorzolamide is associated with plasma proteins. It shows the maximum hypotensive effect after instillation after 2 hours and retains it for 12 hours. When instilled up to 2 times a day by 9-21% reduces intraocular pressure, and when instilled 3 times a day - by 14-24%. Decrease in intraocular pressure at use of 2% of a solution as much as possible can make 4,5-6,1 millimeters of a mercury column. A solution of 3% will be less effective, because it will quickly wash out of the conjunctival cavity, as it causes severe lacrimation. In combination with the appointment of timolol has an additional pronounced effect of 13 to 21%. The minimum effect on blood pressure and heart rate is inhibited by carbonic anhydrase. Diuretics of this group are not used for their intended purpose. About this further.

Indications and dosage

Indication: primary and secondary open-angle glaucoma, ophthalmic hypertension. The drug is shown 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, increased corneal thickness, iridocyclitis, blepharitis, keratitis, conjunctivitis, photophobia, blurred vision, Itching and tingling in the eyes, a feeling of discomfort, Stevens-Johnson syndrome, burning, lacrimation.

This inhibitor of carbonic anhydrase (eye drops) has the following contraindications: excessive sensitivity (to sulfonamides including), childhood, acute liver and kidney disease, pregnancy and breastfeeding.

Preparation: eye drops "Trusopt", containing in 1 ml of a solution of 20 mg of dorzolamide hydrochloride. The capacity of the bottle is 5 ml. Produced in the Netherlands by Merck Sharp & Dohme.

Carbonic anhydrase inhibitors: Brinzolamide (Brinzolamide)

The newest blocker of carbonic anhydrase, which has the ability, when applied locally, 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 interior of the eye. When compared with dorzolamide and acetosolamide, it was found that brinzolamide is the most potent substance of the group of carbonic anhydrase inhibitors. There is evidence that local or intravenous use of Brinzolamide leads to an improvement in the DZN. And it reduces on average by 20% IOP. So not all inhibitors of carbonic anhydrase work. The mechanism of action of Brinzolamide is unique.

Indications and dosages

Indications for use: ophthalmohypertension, open-angle glaucoma. Use 2 times a day by drop.

Side effects: perversion of taste, the feeling of a foreign body, after instillation misting of vision (temporary) and burning sensation. It is transferred locally better than dorzolamide.

Contraindications: excessive sensitivity to the components of the drug (for sulfonamides including), childhood, pregnancy and breastfeeding.

Preparation: eye drops "Azopt", containing in 1 ml of a suspension of 10 mg of Brinzolamide. The capacity of the vial is 5 ml. Produced in the US by Alcon.

What are the inhibitors of carbonic anhydrase?

Derivatives of prostaglandins

Latanoprost (latanoprost) is a selective agonist of prostaglandin receptors. Increases the outflow of intraocular fluid through the vascular membrane of the eyeball, which leads to a decrease in intraocular pressure. Effects on the production of watery moisture does not have. Can change the size of the pupil, but slightly. When instilled, it penetrates in the form of isopropyl ether through the cornea and there it is hydrolyzed to the state of a biologically active acid, which can be determined in the first 4 hours in the intraocular fluid and in the plasma during the first hour. 0,16 l / kg - the volume of distribution. Two hours after the attachment, the maximum concentration of the substance in the aqueous humor is reached, after which it is distributed for the beginning in the anterior segment, i.e., 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. Mainly metabolites are excreted in the urine. Let's consider some more inhibitors of carbonic anhydrase.

Unoprostone (unoprostone)

Isopropyl unoprostone is a docosanoid derivative that rapidly reduces intraocular pressure (IOP) with the help of the latest pharmacological mechanism. Without changing the time of development of intraocular fluid, it facilitates its outflow. Studies have shown that compared to 0.5% maleate timolol, isopropyl unoprostone has a similar or even higher activity with respect to IOP decrease. The drug does not affect accommodation and does not cause a decrease in blood flow in the eye tissues, miosis or mydriasis; The delay in the regeneration of the cornea is also not detected. After topical application, unmodified isotropy of unoprostone in plasma was not detected.

Inhibitors of carbonic anhydrase in glaucoma should be prescribed only by a doctor, self-medication is unacceptable.