Medications to treat glaucoma

Medical treatment of glaucoma began in the late 1800s with physostigmine and pilocarpine. In the United States, glaucoma treatment usually begins with topical medications.

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Description and Physiology

Treatment of glaucoma begins with the use of a standard therapeutic regimen, with the exception of very severe conditions, such as intraocular pressure above 40 mm Hg or a risk of central vision loss. Typically, one drug is prescribed in drops in one eye only, with a repeat examination to assess the effectiveness after 3-6 weeks. Efficacy is determined by comparing the difference in intraocular pressure in the two eyes before treatment and after primary therapy. For example, if before treatment the intraocular pressure was 30 mm Hg OD (oculus dexter - right eye) and 33 mm Hg OS (oculus sinister - left eye), and after primary therapy of the right eye the intraocular pressure became 20 mm Hg OD and 23 mm Hg OS, then the drug is considered ineffective. If after treatment the intraocular pressure is 25 mm Hg OD and 34 mm Hg OS, then the drug is effective.

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

All physicians are advised to carefully read the instructions included in the package when prescribing any medication. The numbers reflect the concentrations of solutions and dosages of drugs taken orally that are used in the United States.

Classes and examples of pharmacological drugs

Medicine	Dosage used
A-Agonists
Apraclonidine (iopidine)	0.5%, 1%
Brimonidine (alphagan)	0.2%
Beta Blockers
Betaxolol (betoptic)	0.5%
Carteolol (Okupress)	1%
Levobunolol (Betagan)	0.25%, 0.5%
Metipranolol (optiPranolol)	0.3%
Timolol polyhydrate (betimol)	0.25%, 0.5%
Timolol (Timoptic)	0.25%, 0.5%
Carbonic anhydrase inhibitors - oral
Acetazolamide (Diamox)	125-500 mg
Methazolamide (neptazan, glauctabs)	25-50 mg
Carbonic anhydrase inhibitors - local
Brinzolamide (azopt)	1%
Dorzolamide (trusopg)	2%
Hyperosmolar drugs
Glycerin (osmoglin)	50% solution
Isosorbide (ismotic)	4% solution
Mannitol (osmitrol)	5%-20% solution
Miotics
Physostigmine (eserine)	0.25%
Pilocarpine hydrochloride (pilocarpine, pilocar)	0.25%, 0.5%, 1%, 2%, 4%, 6%
Pilocarpine nitrate (pilagan)	1%, 2%, 4%
Prostaglandins
Bimatoprost (Lumigan)	0.03%
Latanoprost (xalatan)	0.005%
Travoprost (travatan)	0.004%
Unoprostone isopropyl (rescula)	0.15%
Sympathomimetics
Dipivefrine (propine)	0.1%
Epinephrine (epiphrine)	0.5%, 2%

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Alpha-adrenergic agonists

Mechanism of action: activation of a ₂ -adrenergic receptors 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 prescribed to children under 2 years of age due to the risk of apnea.

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

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Beta-blockers

Mechanism of action: blockade of beta-adrenergic receptors 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 heart block, bronchospasm, fatigue, mood swings, impotence, decreased sensitivity to hypoglycemia symptoms in insulin-dependent diabetes, worsening 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 in this group. Relatively cardioselective drugs may have fewer pulmonary side effects.

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

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

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Carbonic anhydrase inhibitors

Mechanism of action: inhibition of the enzyme carbonic anhydrase reduces the production of water in the ciliary body. When administered parenterally, carbonic anhydrase inhibitors also cause dehydration of the vitreous body.

Side effects

• Local (with local application): bitterness in the mouth.
• Systemic: When applied topically - increased urine output, lethargy, gastrointestinal disturbances, Stevens-Johnson syndrome, theoretical risk of developing aplastic anemia.
• In systemic treatment
  • hypokalemia and acidosis, kidney stones, paresthesia, nausea, cramps, diarrhea, malaise, drowsiness, depression, impotence, unpleasant taste in the mouth, aplastic anemia, Stevens-Johnson syndrome.

Contraindications: allergy to drugs with a sulfo group, hyponatremia or hypokalemia, recent history of kidney stones, taking thiazide diuretics or digitalis preparations.

Hyperosmolar drugs

Mechanism of action: dehydrate the vitreous body and reduce the volume of intraocular fluid by osmotic transition of fluid into the intravascular space. The drugs are administered orally or intravenously.

Side effects

• Mannitol. Congestive heart failure, urinary retention in men, back pain, myocardial infarction, headaches, mental disorders.
• Glycerol. Vomiting, development of congestive heart failure is less likely than with mannitol, other side effects are the same as with mannitol.
• Isosorbide mononitrate. Same as glycerin, except that isosorbide mononitrate may be safer to take if you have diabetes.

Contraindications: congestive heart failure, diabetic ketoacidosis (glycerol), subdural or subarachnoid hemorrhage, previous severe dehydration.

Miotics

Mechanism of action: Direct-acting cholinergics stimulate muscarinic receptors, and indirect-acting cholinergics block acetylcholinesterase. Miotics cause contraction of the pupillary sphincter, which is thought to open the trabecular meshwork and increase outflow through it.

Side effects

Direct acting cholinergics

• Local: pain in the eyebrow area, disruption of the blood-aqueous humor barrier with a closed angle (increases pupillary block and causes anterior displacement of the iridocrystalline diaphragm), decreased twilight vision, varying degrees of myopia, retinal tears and detachment, and possibly anterior subcapsular cataracts.
• Systemic: rare.

Indirect acting cholinergics

• Local: retinal detachment, cataract, myopia, severe miosis, angle closure, increased postoperative bleeding, punctate stenosis, increased formation of posterior synechiae in chronic uveitis.
• Systemic: diarrhea, intestinal spasms, enuresis, increased action of succinylcholine.

Contraindications

• Direct cholinergics: pathology of the retinal periphery, clouding of the central environment, young age (increases myopic effect), uveitis.
• Indirect cholinergics: administration of succinylcholine, predisposition to renal rupture, anterior subcapsular cataract, eye surgery, uveitis.

Prostaglandins

Mechanism of action: Prostaglandin F _2a analogues enhance uveoscleral outflow by increasing the exchange of 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 macular edema and anterior uveitis.
• Systemic: symptoms of systemic upper respiratory tract infection, back and chest pain, myalgia.

Contraindications: pregnancy, it is believed that it cannot be used in inflammatory conditions.

Sympathomimetics

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

Side effects

• Local: in aphakia, cystoid macular edema 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 anterior chamber angle, aphakia, pseudophagia, soft lenses, hypertension and heart disease.

Comments: dipivefrin must be taken for 2-3 months to achieve full effect. Epinephrine has mixed alpha- and beta-mimetic activity.

Combination drug

Currently, only one combination drug is available - cosopt (timolol with dorzolamide), which contains the beta-blocker timolol (0.5%) and the topical carbonic anhydrase inhibitor dorzolamide.

This drug shares the mechanism of action, side effects and contraindications of both beta-blockers and local carbonic anhydrase inhibitors.

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Target

The short-term goal of drug use is to reduce intraocular pressure. Long-term goals are to prevent symptomatic blindness and minimize side effects when using drugs.