When treating glaucoma, the doctor uses all methods to reduce increased intraocular pressure. This, in turn, helps reduce the amount of damage to the optic nerve. As a rule, in the initial stages of the disease, eye drops are used that eliminate intraocular hypertension. An important condition for effective treatment is regular use according to the instructions written by the doctor. If monotherapy is not effective enough, the ophthalmologist usually prescribes eye drops from a different chemical group. These drugs may potentiate each other's effects.
Since all eye drops that are used to treat glaucoma are absorbed into the choroidal vessels, they can penetrate into the systemic circulation in small quantities. Some components of antiglaucoma medications negatively affect the functioning of the heart, blood vessels, and respiratory system. Therefore, it is very important for the doctor to know if the patient has any systemic chronic diseases. If the patient for some reason (health status, low adherence) is not able to regularly instill glaucoma medications, then it is better to choose an alternative method of treatment.
Types of drops that reduce intraocular pressure
Drops for the treatment of glaucoma are produced in large quantities. Each of them contains certain drugs, which can be divided into several groups:
- Based on the active component, beta blockers, prostaglandins, cholinomimetics, etc. are distinguished.
- According to the mechanism for eliminating intraocular hypertension, there are drugs that reduce the synthesis of aqueous humor, drugs that improve its outflow, and combined drugs.
Prostaglandin analogues
Prostaglandins are the safest and most effective agents for the treatment of glaucoma. 2 hours after instillation of this group of medications, the pressure inside the eye begins to decrease, and the maximum effect is observed after 12 hours.
This group of drugs includes Travatan, Tafluprost, Xalatan. All of them appeared relatively recently, but due to their high efficiency and duration of action (up to 24 hours), these drugs have become very popular in the treatment of patients with glaucoma.
Prostaglandins help restore the outflow of aqueous humor through additional pathways. However, these drugs also have some side effects. These include:
- Temporary redness of the eyes as a result of an increase in the diameter of the superficial arteries;
- Changes in the color of the iris due to pigment accumulation;
- Stimulates the growth of eyelash hairs; they also darken and become thicker (this effect is sometimes beneficial and can be used for cosmetic purposes).
Beta blockers
The mechanism of action of beta blockers is to reduce the synthesis of aqueous humor. They begin to act half an hour after instillation, and the effect reaches its maximum after about 2 hours. The frequency of use is higher than that of prostaglandins (usually 2 times a day), which is less convenient for the patient. Often, beta blockers for the treatment of glaucoma are combined with prostaglandins to increase the effectiveness of therapy.
There are a large number of eye drops belonging to this group (Timolol, Okumol, Arutimol, Okumed, Okupress, etc.). The active substance used in the drops is usually the same, so they are all interchangeable.
Beta blockers can have negative effects on body systems, such as causing bradycardia or bronchospasm. Therefore, this group of drugs is not used in patients with concomitant pulmonary emphysema, heart or vascular diseases, or bronchial asthma.
Highly selective beta blockers, which have significantly fewer side effects, include Betoptik.
Carbonic anhydrase inhibitors
Carbonic anhydrase inhibitors include Azopt and Trusopt. The mechanism of their action is associated with inhibition of intraocular moisture production. These medications are quite effective and, at the same time, safe, since there are practically no side effects when using them. The only thing is that patients with certain diseases of the excretory system need to be careful. Typically, carbonic anhydrase inhibitors are prescribed for double use; they are often combined with other groups of drugs (beta blockers, prostaglandins).
Diacarb tablets have a similar effect to Azopt, so it can also be prescribed to patients with glaucoma, especially during an acute attack of intraocular hypertension.
Cholinomimetics
The drugs Pilocarpine and Carbocholine are used to normalize the outflow of aqueous humor through the drainage system. They lead to narrowing of the pupillary opening and contraction of other muscle fibers, as a result of which the angle of the anterior chamber is freed from obstructions. Most often, cholinomimetics are prescribed to patients with angle-closure (narrow-angle) glaucoma to increase the size of the angle. The frequency of use is 1-2 times a day. These drugs are combined with drugs from other pharmacological groups (beta blockers, prostaglandins, carbonic anhydrase inhibitors).
Due to the pronounced narrowing of the pupillary opening, when using these medications, the field of vision may narrow and pain may appear in the temporal, frontal and superciliary areas.
Combination drugs
For the convenience of patients, several eye drops have been developed, consisting of active substances from different groups. This allows you to reduce the number of vials with medications, and sometimes the frequency of instillation.
Most often, ophthalmologists prescribe the following combination drops:
- Xalacom, which includes Timolol and Xalatan;
- Cosopt, consisting of Timolol Trusopt;
- Fotil, which contains Pilocarpine and Timolol.
Azarga
Brinzolamide is a carbonic anhydrase II inhibitor. Due to inhibition of carbonic anhydrase II, the formation of bicarbonate ions is slowed down with a subsequent decrease in sodium and fluid transport, which leads to a decrease in the production of intraocular fluid in the ciliary body of the eye. As a result, intraocular pressure (IOP) decreases.
Timolol is a non-selective beta-adrenergic receptor blocker without sympathomimetic activity, does not have a direct depressive effect on the myocardium, and does not have membrane-stabilizing activity. When applied topically, it reduces intraocular pressure by reducing the formation of aqueous humor and slightly increasing its outflow.
The combined effect of brinzolamide and timolol exceeds the effect of each substance separately.
Pharmacokinetics
When applied topically, brinzolamide and timolol penetrate into the systemic circulation. Brinzolamide is absorbed into erythrocytes as a result of selective binding predominantly to carbonic anhydrase II. Cmax of brinzolamide in erythrocytes is about 18.4 μM. Plasma protein binding is about 60%.
The metabolism of brinzolamide occurs through N-dealkylation, O-dealkylation and oxidation of the N-propyl side chain. The main metabolite is N-desethylbrinzolamide; in the presence of brinzolamide, it binds predominantly to carbonic anhydrase I and also accumulates in erythrocytes. In vitro studies show that the metabolism of brinzolamide is mainly responsible for the CYP3A4 isoenzyme, as well as the CYP2A6, CYP2B6, CYP2C8 and CYP2C9 isoenzymes. Brinzolamide is excreted mainly by the kidneys unchanged - about 60%. About 20% is excreted as metabolites: the main metabolite (N-desethylbrinzolamide) and trace concentrations of other metabolites (N-desmethoxypropyl and O-desmethyl).
Cmax of timolol in blood plasma is about 0.824 ng/ml and remains up to the detection threshold for 12 hours. T1/2 of timolol is 4.8 hours after topical application of Azarga. The metabolism of timolol occurs in two ways: with the formation of an ethanolamine side chain on the thiadiazole ring and with the formation of an ethanol side chain at the morpholine nitrogen and a similar side chain with a carbonyl group connected to the nitrogen. Timolol is metabolized mainly by the CYP2D6 isoenzyme. Timolol and the resulting metabolites are mainly excreted by the kidneys. About 20% of timolol is excreted unchanged, the rest - in the form of metabolites.
Neuroprotectors in the treatment of glaucoma
In the treatment of glaucoma, drugs that have a neuroprotective effect stand out. They help improve microcirculation in the optic nerve area and improve the nutrition of nerve cells. A number of studies have shown the high effectiveness of this group of drugs, which improve the prognosis and course of glaucoma. It is especially advisable to prescribe neuroprotectors in advanced forms of the disease and in advanced cases.
Interestingly, some antiglaucoma drops (beta blockers, prostaglandins) also have a slight neuroprotective effect.
The main groups of neuroprotectors are presented below:
1. Medicines to improve microcirculation (trental, ginkgo biloba, dicynon). 2. Drugs to improve the regeneration of nervous tissue (cinnarizine, picamelon, nootropil, fezam). 3. Substances to activate the nutrition of nerve cells (Semax, Cortexin, retinalamine, Noben, Cerebrolysin). 4. Vitamins and antioxidants (mexidol, emoxipin, aevit, ascorbic acid, vitamins B and E, lutein complex, riboxin, histochrome, mertilen forte, erisod).
Neuroprotectors should definitely be prescribed in the combined treatment of glaucoma. Drugs from different groups combine well with each other and even potentiate the effect. To select the optimal treatment regimen with neuroprotectors, you need to contact an experienced ophthalmologist.
Azarga, 1 piece, 5 ml, eye drops
Systemic effects
Brinzolamide and timolol may be subject to systemic absorption.
Timolol, when applied topically, can cause the same side effects from the cardiovascular system and respiratory system, as well as other undesirable reactions, like systemic beta-blockers.
Hypersensitivity reactions, characteristic of all sulfonamide derivatives, may develop when using the drug AZARGA due to systemic absorption. If serious adverse reactions or hypersensitivity reactions occur, discontinue use of the drug.
Heart disorders
In patients with cardiovascular disease (including ischemic heart disease, Prinzmetal's angina, heart failure) and hypotension, therapy with beta-blockers should be critically evaluated and the possibility of treatment with other active substances considered. Patients with cardiovascular disease should be closely monitored for signs of exacerbation of disease and adverse reactions.
Vascular disorders
Caution should be used in patients with severe impairment/disorder of peripheral circulation (Raynaud's disease or severe Raynaud's syndrome).
Hyperthyroidism
β-blockers may mask the symptoms of hyperthyroidism.
Muscle weakness
β-blockers have been reported to increase muscle weakness that occurs with some symptoms of myasthenia gravis (including diplopia, ptosis and general weakness).
Respiratory system disorders
Respiratory reactions, including death from bronchospasm, have been reported in patients with asthma after taking topical beta-blockers.
Hypoglycemia/diabetes
β-blockers should be prescribed with caution to patients with a tendency to spontaneous hypoglycemia or patients suffering from labile diabetes, since these drugs may mask the symptoms of acute hypoglycemia.
Acid-base imbalance
The development of acid-base imbalance with the use of oral forms of carbonic anhydrase inhibitors has been described. In patients at risk of renal failure, the drug should be used with caution due to the possible risk of metabolic acidosis.
Concentration of attention
Oral carbonic anhydrase inhibitors may affect the ability to perform activities requiring increased alertness and/or physical coordination in elderly patients. These phenomena can be observed because brinzolamide penetrates into the systemic circulation when applied topically.
Anaphylactic reactions
Patients with atopy or a history of severe anaphylactic reactions to various allergens who are receiving beta-blockers may react more strongly to exposure to these allergens and may also be resistant to normal doses of epinephrine for the treatment of anaphylactic reactions.
Choroidal detachment of the eye
Cases of detachment of the choroid have been described when using drugs that prevent the formation of intraocular fluid (including timolol, acetazolamide) after filtering operations.
Surgical anesthesia
The action of β-blockers in ophthalmic preparations can block the systemic effect of β-agonists, incl. adrenaline. The anesthesiologist should be informed that the patient is taking timolol.
Concomitant therapy
When using the drug AZARGA in patients taking systemic α, β-blockers, it is necessary to take into account the possible mutual enhancement of the pharmacological action of the drugs, both in relation to the known systemic effects of β-blockers and in relation to the reduction of IOP. Careful monitoring of such patients is necessary.
The combined use of two local β-blockers is not recommended. There is a potential for increased systemic effects resulting from carbonic anhydrase inhibition in patients taking oral carbonic anhydrase inhibitors and AZARGA. The simultaneous administration of AZARGA and oral carbonic anhydrase inhibitors is not recommended.
Effects on the organ of vision
The effect of brinzolamide on corneal endothelial function in patients with corneal disorders (especially in patients with low endothelial cell counts) has not been studied. In patients wearing contact lenses, it is necessary to carefully monitor the condition of the cornea when using brinzolamide, because Carbonic anhydrase inhibitors may affect corneal hydration. Close monitoring of patients with corneal disorders, such as patients with diabetes mellitus or corneal dystrophy, is recommended.
Benzalkonium chloride
Benzalkonium chloride, which is part of the drug AZARGA, can cause eye irritation and also change the color of soft contact lenses. Contact with soft contact lenses should be avoided.
Before using the drug, contact lenses should be removed and put back no earlier than 15 minutes after using the drug.
AZARGA contains benzalkonium chloride, which can cause punctate keratopathy and/or toxic ulcerative keratopathy. With long-term use of the drug, patients should be carefully monitored.
Liver dysfunction
AZARGA should be used with caution in patients with severe hepatic impairment.
Influence on the ability to drive vehicles and operate machinery. The drug AZARGA has a slight effect on the ability to drive and operate machinery. If the patient experiences temporary blurred vision after using the drug, it is not recommended to drive a car or engage in activities that require increased attention and reaction until they recover. Carbonic anhydrase inhibitors may impair the ability to perform tasks requiring concentration and/or coordination.
