Glaucoma drops

Glaucoma drops are represented by various groups of drugs.

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Beta blockers

Adrenergic neurons secrete norepinephrine at sympathetic postganglionic nerve endings.

There are 4 types of adrenergic receptors:

1. alpha-1 are located in the small arteries, dilator pupillae and Müller's muscle. Excitation causes hypertension, mydriasis and eyelid retraction;
2. alpha-2 - inhibitors of receptors located in the ciliary epithelium. Excitation causes inhibition of aqueous humor secretion and a partial increase in uveoscleral outflow;
3. beta-1 are located in the myocardium and when stimulated cause tachycardia;
4. beta-2 are located in the bronchi and ciliated epithelium. Their excitation leads to bronchospasm and increased secretion of aqueous humor.

Beta blockers neutralize the effect of catecholamines in beta receptors, reduce intraocular pressure, inhibiting the production of aqueous humor. They are used 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 as selective beta blockers are more sensitive to beta-1 receptors. Theoretically, the bronchospastic effect of beta-2 receptor blockade is minimal. Betaxolol is the only selective drug used in the treatment of glaucoma.

Contraindications: severe cardiac dysfunction, atrioventricular block of 2 and 3 degrees, bradycardia, bronchial asthma and obstructive respiratory diseases.

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Timolol

Preparations

• Timoptol 0.25% and 0.5% 2 times a day.
• Timoptol-LA 0.25% and 0.5% once a day.
• Neogel-LA 0.1% 1 time per day.

Local side effects: allergic reaction, pinpoint corneal erosions, decreased tear production.

Systemic side effects most often occur during the first week and are quite serious.

• Bradycardia and hypotension due to beta-1 receptor blockade and a history of severe cardiac pathology are contraindications to the use of beta-blockers.
• Monitoring the patient's pulse before prescribing beta-blockers is mandatory!
• Bronchospasm can be caused by beta-2 receptor blockade and can be fatal in patients with a history of asthma and chronic lung disease.

Other side effects include sleep disturbances, hallucinations, anxiety, depression, fatigue, headache, nausea, dizziness, decreased libido and decreased plasma high-density lipoprotein levels.

Decreased systemic effect of beta-blockers:

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

Other beta blockers

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

Alpha-2 agonists

The drugs reduce intraocular pressure by reducing the secretion of aqueous humor and increasing uveoscleral outflow.

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

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Beta2-alpha prostaglandin analogs

Reduce intraocular pressure by increasing uveoscleral outflow.

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Laganoprost

1. Latanoprost (xalatan) 0.005% is used once a day.
2. It is more effective than timolol, but some patients are resistant to prostaglandin analogues.
3. Local side effects: conjunctival hyperemia, eyelash elongation, hyperpigmentation of the iris and periorbital area. Rarely, if there are risk factors, anterior uveitis and macular edema may occur. Prescribed with caution in uveal glaucoma.
4. Systemic side effects: headaches and upper respiratory tract dysfunction.

Other drugs

1. Travoprost (Travatan) 0.004% is similar to latanoprost, but is sometimes more effective.
2. Bimatoprost (Lumigan) 0.3% - prostamide. In addition to improving uveoscleral outflow, it can improve trabecular outflow.
3. Unoprostone isopropyl (Rescula) 0.15% 2 times a day.

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

Parasympathomimetics

These are parasympathomimetics that stimulate muscarinic receptors of the sphincter of the pupil and ciliary body.

Indications for use:

• In primary open-angle glaucoma, intraocular pressure is reduced by contracting the ciliary muscle, increasing the outflow of aqueous humor through the trabecular meshwork.
• In primary angle-closure glaucoma, contraction of the pupillary sphincter and miosis allow the peripheral iris to move away from the trabecular zone, opening the angle-closure glaucoma. It is necessary to reduce the intraocular pressure with systemic drugs before miotics take effect.

Pilocarpine

Indications

• Pilocarpine 1%, 2%, 3%, 4% up to 4 times a day as monotherapy. In combination with beta-blockers, two instillations are sufficient.
• Pilocarpine gel (Pilogel) consists of pilocarpine adsorbed on a gel. It is used once before bedtime so that the myopia and miosis caused by the drug occur at night. The main inconvenience is the development of superficial corneal edema in 20% of cases, but it rarely affects vision.

It is as effective as beta blockers.

Local side effects: miosis, pain in the superciliary arch, myopization and cataractogenicity. Visual disturbances seem more pronounced.

Systemic side effects are minor.

Carbonic anhydrase inhibitors

Carbonic anhydrase inhibitors are classified as sulfonamides by chemical composition. The mechanism of intraocular pressure reduction is associated with inhibition of aqueous humor production.

• Dorzolamide (Trusopt) 2% 3 times a day. Comparable in effectiveness to betaxolol, but weaker than timolol. The main local side effect is allergic conjunctivitis.
• Brinzolamide (Azopt) 1% 3 times daily. Similar to dorzolamide, but has a less pronounced local reaction.

Combination drugs

Combined drugs enhance the hypotensive effect, are more effective and convenient, making compliance with the regimen realistic. These include:

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

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Systemic carbonic anhydrase inhibitors

Prescribed in short courses; long-term use is justified only in cases of high risk of visual impairment caused by long-term high intraocular pressure.

Preparations

• Acetazolamide tablets 250 mg. Daily dose 250-1000 mg. Onset of action after 1 hour, maximum effect after 4 hours, duration up to 12 hours.
• Acetazolamide capsules 250 mg. Daily dose 250-500 mg, duration of action up to 24 hours.
• Acetazolamide injection 500 mg. Onset of action is almost immediate, peak action after 30 min, duration up to 4 h. This is the only form used in acute attack of glaucoma.
• Dichlorphenamide tablets 50 mg. Daily dose 50-100 mg (2 times daily). Onset of action within 1 hour, peak action after 3 hours, duration up to 12 hours.
• Methazolamide tablets 50 mg. Daily dose 50-100 mg (2-3 times daily). Onset of action after 3 hours, maximum effect after 1 hour, duration of action up to 10-11 hours. This is a good alternative to acetazolamide in terms of duration of 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) is common and usually safe. Further treatment is possible if the patient expresses consent and denies intolerance to 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 eliminate these symptoms.

Rare

• Gastrointestinal tract: stomach discomfort, abdominal cramps, diarrhea and nausea. Occur independently of the malaise and do not lead to changes in the chemical composition of the blood;
• nephrolithiasis.
• Stevens-Johnson syndrome is a characteristic reaction to sulfonamide derivatives;
• Hematopoietic disorders are extremely rare:
  • Dose-dependent effect on the hematopoietic function of the bone marrow, which is usually restored after discontinuation of the drug.
  • Specific aplastic anemia, not related to the dose, which is fatal in 50% of cases. This can occur even after a single dose of the drug, but is more often observed in the first 2-3 months and very rarely after 6 months of treatment.

Side effects of carbonic anhydrase inhibitors

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

Osmotic drugs

Osmotic pressure depends on the number of particles in the solution, not their size, so low-molecular solutions are characterized by a greater osmotic effect. Osmotic drugs remain in the intravascular bed, increasing the osmolarity of the blood. They lower 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. When it is destroyed, the effect of further use is lost, so hyperosmotic agents are limited in uveitic glaucoma, which is characterized by a violation of the hemato-ophthalmic barrier.

Clinical application

It is used when the hypotensive effect of local therapy at the maximum regimen is insufficient,

• Acute attack of glaucoma,
• Preoperative preparation when high intraocular pressure poses a risk of lens dislocation into the anterior chamber.

This preparation should be fairly quick, after which the patient should refrain from drinking liquids if thirst occurs.

Preparations

• Glycerol is taken orally, it has a sweet taste and can cause nausea. Adding lemon (not orange) juice helps to avoid it. The dose is calculated depending on weight: 1 g / kg of body weight or 2 ml / kg of body weight (50% solution). The maximum effect occurs after 1 hour and lasts up to 3 hours. Glycerol should be prescribed with caution to patients with compensated diabetes.
• Isosorbide is taken 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 as a hyperosmotic drug. The dose is calculated depending on weight: 1 g / kg or 5 ml / kg (20% aqueous solution). The maximum effect is achieved within 30 minutes and lasts up to 6 hours.

Side effects

1. Cardiovascular decompensation due to increased extracellular volume, so such drugs should be administered with caution to patients with chronic cardiac and renal pathologies.
2. Urinary retention in elderly men after intravenous administration. Urinary catheterization is necessary for prostate disease.
3. Other side effects include headache, lower back pain, nausea and impaired consciousness.

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