Drugs for the treatment of glaucoma

Medical treatment of glaucoma began in the late 1800s, using physostigmine and pilocarpine. In the US, the treatment of glaucoma usually begins with the appointment of local drugs.

[1], [2]

Description and Physiology

Treatment of glaucoma begins with the use of a standard therapeutic regimen, except for very severe conditions, when, for example, intraocular pressure is above 40 mm Hg. Or there is a risk of loss of central vision. Usually, one drug is prescribed in drops only in one eye with a second examination to evaluate the efficacy in 3-6 weeks. Efficacy is determined by comparing the difference in intraocular pressure on the two eyes before the treatment and after the initial therapy. For example, if prior to treatment, intraocular pressure was 30 mm Hg. OD (oculus dexter - right eye) and 33 mmHg. OS (oculus sinister - left eye), and after primary therapy of the right eye, intraocular pressure became 20 mm Hg. OD and 23 mm Hg. OS, it is considered that the drug is ineffective. If after treatment, intraocular pressure is 25 mm Hg. OD and 34 mm Hg. OS, then the drug is effective.

There are several different classes of medicines. All these drugs reduce the level of intraocular pressure by various mechanisms. The magnitude of intraocular pressure is determined by the balance between secretion and outflow of aqueous humor. Drugs either inhibit the secretion, or increase the outflow. The following chapters describe the mechanisms of action, the frequent side effects and contraindications for different classes of drugs.

All doctors are recommended, when prescribing a drug, carefully read the instructions enclosed in the package. The figures reflect the concentrations of solutions and dosages of drugs taken orally that are used in the US.

Classes and examples of pharmacological drugs

Medicine	Used dosage
A-Agonists
Apraclonidine (yopidine)	0.5%, 1%
Brimonidine (alfa)	0.2%
Beta-Blockers
Betaxolol (Betoptik)	0.5%
Carotenol (Ocupress)	1%
Levobunolol (betagan)	0.25%, 0.5%
Metipranolol (optPranolol)	0.3%
Timolol polyhydrate (betimol)	0.25%, 0.5%
Timolol (Timothy)	0.25%, 0.5%
Carbonic anhydrase inhibitors - oral
Acetazolamide (diamox)	125-500 mg
Metazolamide (neptazan, glauktabs)	25-50 mg
Carbonic anhydrase inhibitors - local
Brinzolamide (azopt)	1%
Dorzolamide (trusopg)	2%
Hyperosmolar preparations
Glycerin (Osmoglin)	50% solution
Isosorbide (ismatik)	4% solution
Mannitol (osmithrol)	5% -20% solution
Myotics
Physostigmine (eserine)	0.25%
Pilocarpine hydrochloride (pilocarpine, pilocar)	0.25%, 0.5%, 1%, 2%, 4%, 6%
Pilocarpine nitrate (Pylaganum)	1%, 2%, 4%
Prostaglandins
Bimatoprost (lumigan)	0.03%
Latanoprost (xalatan)	0.005%
Travoprost (travatan)	0.004%
Unoprostone isopropyl (resula)	0.15%
Sympathomimetics
Dipivefrin (propyne)	0.1%
Epinephrine (epifrine)	0.5%, 2%

[3], [4], [5], [6], [7], [8], [9]

Alpha-adrenoagonists

Mechanism of action: activation of a _2- adrenoreceptors of the ciliary body inhibits the secretion of aqueous humor.

Side effects: local irritation, allergy, mydriasis, dry mouth, dry eyes, arterial hypotension, lethargy.

Contraindications: taking monoamine oxidase inhibitors, brimonidine should not be administered to children younger than 2 years due to the threat of apnea.

Note: apraklonidine is intended for short-term use and prevention of intraocular pressure jumps after laser treatment.

[10], [11], [12],

Beta-blockers

The mechanism of action: blockade of beta-adrenoreceptors of the ciliary body reduces intraocular pressure by reducing the production of aqueous humor.

Side effects.

• Local: blurred vision, corneal anesthesia and superficial punctate keratitis.
• Systemic: bradycardia or blockade of the heart, bronchospasm, fatigue, mood swings, impotence, decreased sensitivity to symptoms of hypoglycemia in insulin-dependent diabetes, aggravation of myasthenia gravis.

Contraindications: asthma, severe chronic obstructive pulmonary diseases, bradycardia, heart block, congestive heart failure, myasthenia gravis.

Comments: There are non-selective and relatively cardioselective drugs of this group. Relatively cardioselective drugs can give fewer side effects from the lungs.

Relative receptor selectivity of various drugs from the group of beta-blockers

• Preparation / Relative specificity of action on receptors
• Betaxolol / Relatively cardioselective
• Carotenol / Non-selective, has intrinsic sympathomimetic activity
• Levobunolol / Non-selective, long half-life
• Metipranolol / Nonselective
• Timolol polyhydrate / Nonselective
• Timolola Maleate / Nonselective

[13], [14], [15], [16], [17]

Inhibitors of carbonic anhydrase

Mechanism of action: inhibition of the enzyme carbonic anhydrase reduces the production of moisture in the ciliary body. In parenteral administration, carbonic anhydrase inhibitors also cause dehydration of the vitreous.

Side effects

• Local (with topical application): bitterness in the mouth.
• Sitemnie: With topical application - an increase in the volume of excreted urine, lethargy, gastrointestinal disorders, Stevens-Johnson syndrome, the theoretical risk of developing aplastic anemia.
• With systemic treatment
  • hypokalemia and acidosis, formation of kidney stones, paresthesia, nausea, convulsions, diarrhea, malaise, drowsiness, depression, impotence, bad taste in the mouth, aplastic anemia, Stevens-Johnson syndrome.

Contraindications: allergy to drugs with sulfo-group, hyponatremia or hypokalemia, kidney stones in anamnesis recently, the use of thiazide diuretics or digitalis preparations.

Hyperosmolar preparations

The mechanism of action: dehydrates the vitreous body and reduces the volume of intraocular fluid by osmotic transfer of fluid into the intravascular space. Preparations are administered orally or intravenously.

Side effects

• Mannitol. Congestive heart failure, urinary retention in men, back pain, myocardial infarction, headaches, mental disorders.
• Glycerol. Vomiting, the development of congestive heart failure is less likely than with the administration of mannitol, the other side effects, like mannitol.
• Isosorbide mononitrate. Same as glycerin, except that perhaps the intake of isosorbide mononitrate is safer in diabetes.

Contraindications: congestive heart failure, diabetic ketoacidosis (glycerol), subdural or subarachnoid hemorrhage, which had previously been severe dehydration.

Myotics

Mechanism of action: direct-acting cholinergetics stimulate muscarinic receptors, and cholinergics of indirect action block acetylcholinesterase. Myotics cause a reduction in the sphincter of the pupil, which is believed to contribute to the discovery of the trabecular network and increases the outflow through it.

Side effects

Cholinergics of direct action

• Local: pain in the eyebrows, violation of the barrier "blood-watery moisture", with a closed angle (enhances the pupillary block and causes the displacement of the iris-lens diaphragm anteriorly), a decrease in twilight vision, various degrees of myopia, ruptures and detachment of the retina, and possibly the anterior subcapsular cataracts.
• System: rarely.

Cholinergics of indirect action

• Local: retinal detachment, cataract, myopia, strong miosis, angle closure, increased post-operative bleeding, pinpoint stenosis, reinforced posterior synechia formation in chronic uveitis.
• Systemic: diarrhea, intestinal spasms, enuresis, increased action of succinylcholine.

Contraindications

• Direct cholinergetics: pathology of the periphery of the retina, turbidity of the central environment, young age (increased myopic effect), uveitis.
• Indirect cholinergetics: administration of succinylcholine, predisposition to rupture of the kidney, anterior subcapsular cataract, eye surgery, uveitis.

Prostaglandins

Mechanism of action: prostaglandin F _2a analogues enhance uveoscleral outflow, increasing the exchange of the extracellular matrix on the surface of the ciliary body.

Side effects

• Local: increased melanin pigmentation of the iris, blurred vision, redness of the eyelids, there are reports of cystic edema of the macula and anterior uveitis.
• Systemic: symptoms of systemic upper respiratory tract infection, pain in the back and chest, myalgia.

Contraindications: pregnancy, believe that it can not be used in inflammatory conditions.

Sympathomimetics

Mechanism of action: in the ciliary body, the reaction of various beta-adrenostimulation increases the production of moisture, and a-stimulation reduces its production); in the trabecular network, beta-adrenostimulation causes an increase in outflow along the traditional and alternative routes. In general, reduce intraocular pressure.

Side effects

• Local: with aphakia, cystic edema of the macula is possible (more likely for epinephrine than for dipivefrin), mydriasis, withdrawal syndrome in the form of hyperemia, blurred vision, adrenochromic deposits, allergic blepharoconjunctivitis.
• Systemic: tachycardia / extrasystole, arterial hypertension, headache.

Contraindications: narrow and closed angle of the anterior chamber, aphakia, pseudophagia, soft lenses, hypertension and heart diseases.

Comments: dipivephrine should be taken 2-3 months before the full effect is achieved. Epinephrine has a mixed alpha and beta-mimetic activity.

Combined drug

Currently, only one combined preparation is available - a Kosopt (timolol with dorzolamide), which contains a beta-adrenoblocker timolol (0.5%) and a local inhibitor of carbonic anhydrase dorzolamide.

For this preparation, the mechanism of action, side effects and contraindications of both beta-blockers and local inhibitors of carbonic anhydrase are characteristic.

[18], [19], [20]

Goal

The short-term goal of using drugs is to reduce intraocular pressure. Long-term goals - prevention of symptomatic blindness and minimization of side effects when using medicines.