Drops from glaucoma

Drops from glaucoma are represented by different groups of drugs.

[1], [2], [3], [4], [5], [6],

Beta-blockers

Adrenergic neurons secrete noradrenaline in sympathetic postganglionic nerve endings.

Adrenergic receptors have 4 types:

1. Alpha-1 are located in small arteries, the dilator pupil and the muscle of Muller. Excitation causes hypertension, mydriasis and retraction of the eyelid;
2. alpha-2 - inhibitors of the receptorone located in the ciliary epithelium. Excitation causes oppression of the secretion of aqueous humor and a partial increase in uveoscleral outflow;
3. beta-1 are located in the myocardium, with stimulation cause tachycardia;
4. Beta-2 are located in the bronchi and ciliary epithelium. Their excitement leads to bronchospasm and increased secretion of watery moisture.

Beta-blockers neutralize the effect of catecholamines in beta receptors, reduce intraocular pressure, inhibiting the production of aqueous humor. Applied for all types of glaucoma, but about 10% of the population are not sensitive to them. Beta-blockers can be non-selective and selective. Non-selective beta-blockers equally block beta-1 and beta-2 receptors, and how selective beta-blockers are more sensitive to beta-1 receptors. Theoretically, the bronchospastic effect of blockade of beta-2 receptors is minimal. Betaxolol is the only selective drug used in the treatment of glaucoma.

Contraindications: marked violations of cardiac activity, antrioventricular blockade of 2 and 3 degrees, bradycardia, bronchial asthma and obstructive diseases of the respiratory system.

[7], [8], [9], [10], [11]

Timolol

Preparations

• Timptol 0.25% and 0.5% 2 times a day.
• Timothol-LA 0.25% and 0.5% I once a day.
• Neogel-LA 0.1% once a day.

Local side effects: allergic reaction, pinpoint erosion of the cornea, decreased production of tears.

Systemic side effects often occur within the first week, and they are serious enough.

• Bradycardia and hypotension due to blockade of beta-1 receptors and severe heart pathology in a history are a contraindication to the appointment of beta-blockers.
• Control of the patient's pulse before the appointment of beta-blockers is mandatory!
• Bronchospasm can be caused by the blocking of beta-2 receptors and be fatal in asthma and chronic pulmonary pathology in history.

Other side effects: sleep disturbance, hallucinations, anxiety, depression, fatigue, headache, nausea, dizziness, decreased libido and a reduction in high-density plasma lipoprotein.

Reduction of the systemic action of beta-blockers:

• After installation of the preparation with closed eyes, press the area of the lower lacrimal point for 3 minutes. It also prolongs its contact with the tissues of the eye and increases the therapeutic effect.
• Simple closing of eyes for 3 minutes after instillation will reduce systemic uptake up to 50%.

Other beta blockers

1. Betaxolol (Betoptik) 0,5% 2 times a day. The hypotensive effect is less than in timolol, but it has a stabilizing effect on visual functions (visual fields). Betaxolol enhances the retinal blood flow, increasing perfusion pressure;
2. Levobunolol (betagan) 0.5%, for hypotensive efficacy is not inferior to timolol. Often, a single instillation per day is sufficient.
3. Carotenol (theoptical) 1% and 2% is not inferior to timolol, it has an additional sympathomimetic effect, which affects selectively the eyes, and not the cardiopulmonary system, causing bradycardia to a lesser degree than timolol.
4. Metipranolol 0.1% and 0.3% 2 times a day. The action is similar to timolol, it is produced without preservative. Usually used in patients with an allergic reaction to preservatives or when wearing soft contact lenses that contain benzalkonium hydrochloride. Sometimes it can cause anterior uveitis.

Alpha-2 agonists

Drugs reduce intraocular pressure by reducing the secretion of watery moisture and increasing the out-scleral outflow.

1. Brimonidine (alfagan) 0.2% 2 times a day is a highly selective alpha-2-agonist with an additional neuroprotective effect. Its effectiveness is less than that of timolol, but higher than betaxolol. There is additivity with beta-blockers. The most frequent local side effect is allergic conjunctivitis, which can manifest even a year after the start of therapy. Systemic side effects: dry mouth, drowsiness and fatigue.
2. Aproclonidine (lopidin) 0.5% and 1% are used after laser surgery of the anterior segment to prevent acute ophthalmic hypertension. The drug is not suitable for long-term use because of tachyphylaxis (loss of therapeutic effect) and a high percentage of local side effects.

[12], [13], [14], [15]

Analogues of beta2-alpha prostaglandins

Decrease intraocular pressure, increasing the out-scleral outflow.

[16], [17], [18], [19]

Laganoprost

1. Apply latanoprost (xalatan) 0.005% once a day.
2. It is superior to timolol in effectiveness, but some patients are resistant to prostaglandin analogues.
3. Local side effects: conjunctival hyperemia, lengthening of eyelashes, hyperpigmentation of the iris and periorbital zone. Rarely, if there is a risk factor, there may be anterior uveitis and macular edema. Assign with caution in postureal glaucoma.
4. Systemic side effects: headaches and upper respiratory tract disorders.

Other drugs

1. Travoprost (travatan) 0.004% is similar to latanoprost, but sometimes more effective.
2. Bimatoprost (lumigan) 0.3% - prostamide. In addition to improving uveoscleral outflow may improve trabecular outflow.
3. Unoprostone isopropyl (res) 0.15% 2 times a day.

The hypotensive effect is not as pronounced as that of latapoprost, and the drug is not sufficient for monotherapy. Sometimes a combination with latanoprost is possible.

Parasympathomimetics

This parasympatomimetiki, stimulating muscarin-like receptors of the sphincter of the pupil and ciliary body.

Indications for use:

• With primary open-angle glaucoma, intraocular pressure is reduced by contraction of the ciliary muscle, increasing the outflow of watery moisture through the trabecular network.
• With primary closed-angle glaucoma, the reduction in the pupil sphincter and miosis allows the peripheral part of the iris to move away from the trabecular area, opening the CCP. It is necessary to reduce intraocular pressure using systemic drugs before miotics act.

Pilocarpine

Indications

• Pilocarpine 1%, 2%, 3%, 4% up to 4 times a day as a monotherapy. In combination with beta-blockers, two-fold instillation is sufficient.
• Pilocarpine gel (pialogel) consists of pilocarpine adsorbed on the gel. Apply once before bedtime to cause myopia and miosis caused by the drug at night. The main disadvantage is the development of a superficial edema of the cornea in 20% of cases, but it rarely affects the eyesight.

The effectiveness is not inferior to beta-blockers.

Local side effects: miosis, pain in the region of the superciliary arches, myopilation and cataractogenicity. The visual disturbances seem more pronounced.

Systemic side effects are minor.

Inhibitors of carbonic anhydrase

Inhibitors of carbonic anhydrase are classified by chemical composition as sulfanilamides. The mechanism of reducing intraocular pressure is associated with the suppression of watery moisture production.

• Dorzolamide (trusopt) 2% 3 times a day. In terms of effectiveness, it is comparable with betaxolode, but weaker than timolol. The main local side effect is allergic conjunctivitis.
• Brinzolamide (azopt) 1% 3 times a day. It is similar to dorzolamide, but has a less pronounced local response.

Combined preparations

Combined drugs enhance the hypotensive effect, are more effective and convenient, making compliance with the regime real. They include:

• Kosopt (timolol + dorzolamide) 2 times a day.
• Xalacom (timolol + latanoprost) 1 time per day.
• TimPilo (timolol + pilocarpine) 2 times a day.

[20], [21], [22], [23], [24],

Systemic inhibitors of carbonic anhydrase

Assign a short course, long-term use is justified only at a high risk of reducing visual function, caused by a long-lasting high level of intraocular pressure.

Preparations

• Acetazolamide tablets of 250 mg. The daily dose of 250-1000 mg. The onset of action after 1 hour, the maximum effect after 4 hours, the duration of up to 12 hours.
• Acetazolamide capsules 250 mg each. The daily dose of 250-500 mg, the duration of the action up to 24 hours.
• Acetazolamide for injection of 500 mg. The onset of action is almost immediate, peak action in 30 minutes, duration up to 4 hours. This is the only form used for an acute attack of glaucoma.
• Dichlorophenamide tablets of 50 mg. The daily dose of 50-100 mg (2 times daily). The beginning of the action within 1 hour, peak action after 3 hours, duration up to 12 hours.
• Metazolamide tablets of 50 mg. The daily dose of 50-100 mg (2-3 times daily). The onset of action after 3 hours, the maximum effect after 1 hour, the duration of the action is up to 10-11 hours. This is a good alternative to acetazolamide for the duration of the action.

Systemic side effects

Long-term use of carbonic anhydrase inhibitors is often accompanied by systemic side effects, which should be reported to the patient.

Frequent

• paresthesia (tingling in the fingers, toes, and sometimes - in the mucocutaneous junctions) are frequent and usually safe. Further treatment is possible if the patient agrees and denies the intolerance of possible manifestations.
• general malaise in the form of weakness, fatigue, depression, weight loss and decreased libido. An additional 2-week course of sodium acetate will completely relieve these symptoms.

Rare

• gastrointestinal tract: gastric discomfort. Abdominal cramps, diarrhea and nausea. They arise regardless of the discomfort and do not lead to a change in the chemical composition of the blood;
• nephrolithiasis.
• Stevens-Johnson syndrome is a characteristic reaction to sulfanylamide derivatives;
• violations of hematopoiesis extremely rare:
  • Dose-dependent effects on the hematopoietic function of the bone marrow, which is usually restored after the drug is discontinued.
  • Specific aplastic anemia, not associated with a dose at which a lethal outcome is possible in 50% of cases. This may occur after a single dose, but more often in the first 2-3 months and very rarely - 6 months after the start of treatment.

Side effects of carbonic anhydrase inhibitors

• Malaise, fatigue, depression, anorexia, weight loss, decreased libido
• Gastrointestinal complex: abdominal hypersecretion, spasms, diarrhea
• Stevens-Johnson syndrome (hematopoiesis)

Osmotic preparations

The osmotic pressure depends on the number of particles in the solution, and not on their size, so low molecular weight solutions are characterized by a large osmotic effect. Osmotic drugs remain in the intravascular bed, increasing the osmolarity of the blood. They lower the intraocular pressure and create an osmotic gradient between the blood and the vitreous body, dehydrating the latter. The higher the gradient, the greater the decrease in intraocular pressure. To achieve this effect, the hyperosmotic agent should not penetrate the hemato-ophthalmic barrier. With its destruction, the effect of further use is lost, so hyperosmotic agents are limited in post-glaucoma, which is characterized by a violation of the hemato-ophthalmic barrier.

Clinical use

Applied with insufficient hypotensive effect of local therapy at the maximum mode,

• Acute attack of glaucoma,
• Preoperative preparation, when with high intraocular pressure there is a risk of lens dislocation in the anterior chamber.

This preparation should be fast enough, after it a patient should refrain from taking fluids when thirst occurs.

Preparations

• Glycerol is used orally, it has a sweet taste and can cause nausea. Adding lemon (not orange) juice allows it to be avoided. The dose is calculated depending on the weight: 1 g / kg body weight or 2 ml / kg body weight (50% solution). The maximum of action occurs in 1 hour and lasts up to 3 hours. Glycerol should be used with caution in patients with compensated diabetes.
• Isosorbide is used orally, it has a mint flavor and does not affect glucose metabolism, so it can be used for diabetes without insulin support. The dose is the same as when taking glycerol.
• Mannitol is widely used intravenously and as a hyperosmotic drug. The dose is calculated as a function of weight: 1 g / kg or 5 ml / kg (20% aqueous solution). The maximum action is achieved within 30 minutes and lasts up to 6 hours.

Side effects

1. Cardiovascular decompensation due to an increase in extracellular volume, so these drugs should be administered with caution to patients with chronic cardiac and renal pathologies.
2. Retention of urination in elderly men after intravenous administration. It is necessary to catheterize the bladder in case of prostate disease.
3. Other side effects: headache, back pain, nausea and impaired consciousness.

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