Levobunolol (trade names AKBeta, Betagan, Vistagan, among others) is a non-selective

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...

. It is used

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

ly in the form of eye drops to manage

ocular hypertension Ocular hypertension is the presence of elevated fluid pressure inside the eye (intraocular pressure), usually with no optic nerve damage or visual field loss. For most individuals, the normal range of intraocular pressure is between 10 mmHg and ...

(high pressure in the eye) and open-angle

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

Contraindications

Like other non-selective beta blockers, levobunolol is contraindicated in patients with airway diseases such as

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

and severe

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...

(COPD), as well as heart problems such as

sinus bradycardia Sinus bradycardia is a sinus rhythm with a reduced rate of electrical discharge from the sinoatrial node, resulting in a bradycardia, a heart rate that is lower than the normal range (60–100 beats per minute for adult humans). Signs and sympt ...

, second- or third-degree

atrioventricular block Atrioventricular block (AV block) is a type of heart block that occurs when the electrical signal traveling from the atria, or the upper chambers of the heart, to ventricles, or the lower chambers of the heart, is impaired. Normally, the sinoatr ...

sick sinus syndrome Sinus node dysfunction (SND), also known as sick sinus syndrome (SSS), is a group of abnormal heart rhythms (arrhythmias) usually caused by a malfunction of the sinus node, the heart's primary pacemaker. Tachycardia-bradycardia syndrome is a varia ...

, and

cardiogenic shock Cardiogenic shock is a medical emergency resulting from inadequate blood flow to the body's organs due to the dysfunction of the heart. Signs of inadequate blood flow include low urine production (<30 mL/hour), cool arms and legs, and decreased ...

. on levobunolol. Combination with MAO-A inhibitors is also contraindicated because it could cause a dangerous rise in blood pressure. Levobunolol is not useful for the treatment of closed-angle glaucoma.

Side effects

The most common side effect is eye irritation felt as stinging or burning, which occurs in up to a third of patients.

Blepharoconjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...

occurs in up to 5% of patients. Rarer adverse effects include

keratitis Keratitis is a condition in which the human eye, eye's cornea, the clear dome on the front surface of the eye, becomes inflammation, inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following sy ...

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

and increased

lacrimation Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...

. Allergies are rare, but seem to be more common than under the related drug

timolol Timolol is a beta blocker medication used either by mouth or as eye drops. As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. By mouth it is used for high blood pressure, chest ...

. If the substance reaches the

nasal mucosa The nasal mucosa lines the nasal cavity. It is part of the respiratory mucosa, the mucous membrane lining the respiratory tract. The nasal mucosa is intimately adherent to the periosteum or perichondrium of the nasal conchae. It is continuous w ...

via the

tear duct The nasolacrimal duct (also called the tear duct) carries tears from the lacrimal sac of the eye into the nasal cavity. The duct begins in the eye socket between the maxillary and lacrimal bones, from where it passes downwards and backwards. The o ...

, it can be absorbed into the bloodstream and cause systemic side effects. These include

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

(low blood pressure) and other effects on the heart and circulatory system, breathing problems in people with asthma, and skin symptoms such as itching and aggravation of

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...

Interactions

Even in the form of eye drops, levebunolol may cause hypotension when combined with

alpha blocker Alpha blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors ( α-adrenoceptors). Historically, alpha-blockers were used as a tool for p ...

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

s, and other drugs that lower blood pressure. It can also cause severe

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

(''high'' blood pressure) when combined with sympathomimetic drugs or MAO-A inhibitors,

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

(low heart rate) when combined with

antiarrhythmic Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a class of drugs that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia. M ...

s or

mefloquine Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria. When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. It ...

, and

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

(low blood sugar) when combined with

antidiabetic drug Drugs used in diabetes treat types of diabetes mellitus by decreasing blood sugar level, glucose levels in the blood. With the exception of Insulin (medication), insulin, most GLP-1 receptor agonists (liraglutide, exenatide, and others), and pra ...

s such as

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

Pharmacology

Mechanism of action

Levobunolol is a non-cardioselective beta blocker, that is, it blocks beta-1 receptors as well as beta-2 receptors. The latter type dominates in the

ciliary body The ciliary body is a part of the eye that includes the ciliary muscle, which controls the shape of the lens, and the ciliary epithelium, which produces the aqueous humor. The aqueous humor is produced in the non-pigmented portion of the ciliary ...

, where it controls

aqueous humour The aqueous humour is a transparent water-like fluid similar to blood plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the po ...

production. Blocking this type of receptor reduces aqueous humour production, lowering

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

. The substance has no relevant

membrane stabilizing effect Membrane stabilizing effects involve the inhibition or total abolishing of action potentials from being propagated across the membrane. This phenomenon is common in nerve tissues as they are the carrier of impulses from the periphery to the central ...

intrinsic sympathomimetic activity Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention). ...

. Like other beta blockers, and unlike the anti-glaucoma medication

pilocarpine Pilocarpine, sold under the brand name Pilopine HS among others, is a lactone alkaloid originally extracted from plants of the Pilocarpus genus. It is used as a medication to reduce pressure inside the eye and treat dry mouth. As an eye drop ...

, levobunolol has no effect on accommodation and pupil size.

Pharmacokinetics

The substance quickly penetrates the

cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...

and reaches the aqueous humour. It is reduced to dihydrolevobunolol, which is equally active, in the eye's tissues. The drug starts to lower intraocular pressure within an hour, reaches its maximum effect after two to six hours, and remains effective for up to 16 hours. It has an

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

of six hours and is mainly excreted via the kidney.

Chemistry

Levobunolol is the pure L-

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

of bunolol and has more than 60 times the pharmacological activity of D-bunolol. It is used as the

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...

, which melts at and is soluble in water and

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

and slightly soluble in

ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

References

* * * {{Adrenergic receptor modulators Beta blockers N-tert-butyl-phenoxypropanolamines Ophthalmology drugs Tetralones