Levobunolol

Last updated
Levobunolol
Levobunolol.svg
Clinical data
Trade names AKBeta, Betagan, Vistagan, others
AHFS/Drugs.com Monograph
MedlinePlus a686011
Pregnancy
category
  • C
Routes of
administration
Topical eye drop
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 7.5% (rabbit eye)
Metabolites dihydrolevobunolol (equally active)
Onset of action ≤ 1 hour
Elimination half-life 6 hours [2]
Duration of action up to 16 hours
Excretion mostly renal
Identifiers
  • (S)-5-{[3-(tert-Butylamino)-2-hydroxypropyl]oxy}-3,4-dihydronaphthalen-1(2H)-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C17H25NO3
Molar mass 291.391 g·mol−1
3D model (JSmol)
Melting point 209 to 211 °C (408 to 412 °F) (hydrochloride)
Solubility in water soluble (hydrochloride)
  • O=C2c1cccc(OC[C@@H](O)CNC(C)(C)C)c1CCC2
  • InChI=1S/C17H25NO3/c1-17(2,3)18-10-12(19)11-21-16-9-5-6-13-14(16)7-4-8-15(13)20/h5-6,9,12,18-19H,4,7-8,10-11H2,1-3H3/t12-/m0/s1 Yes check.svgY
  • Key:IXHBTMCLRNMKHZ-LBPRGKRZSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Levobunolol (trade names AKBeta, Betagan, Vistagan, among others) is a non-selective beta blocker. It is used topically in the form of eye drops to manage ocular hypertension (high pressure in the eye) and open-angle glaucoma. [3]

Contents

Contraindications

Like other non-selective beta blockers, levobunolol is contraindicated in patients with airway diseases such as asthma and severe chronic obstructive pulmonary disease (COPD), as well as heart problems such as sinus bradycardia, second- or third-degree atrioventricular block, sick sinus syndrome, and cardiogenic shock. [3] [4] Combination with MAO-A inhibitors is also contraindicated because it could cause a dangerous rise in blood pressure. [2]

Levobunolol is not useful for the treatment of closed-angle glaucoma. [2]

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 occurs in up to 5% of patients. Rarer adverse effects include keratitis, edema and increased lacrimation. [3] [4] Allergies are rare, but seem to be more common than under the related drug timolol. [2]

If the substance reaches the nasal mucosa via the tear duct, it can be absorbed into the bloodstream and cause systemic side effects. These include orthostatic hypotension (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. [2]

Interactions

Even in the form of eye drops, levebunolol may cause hypotension when combined with alpha blockers, calcium channel blockers, tricyclic antidepressants, and other drugs that lower blood pressure. It can also cause severe hypertension (high blood pressure) when combined with sympathomimetic drugs or MAO-A inhibitors, bradycardia (low heart rate) when combined with antiarrhythmics or mefloquine, and hypoglycemia (low blood sugar) when combined with antidiabetic drugs such as insulin. [2]

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, where it controls aqueous humour production. Blocking this type of receptor reduces aqueous humour production, lowering intraocular pressure. The substance has no relevant membrane stabilizing effect or intrinsic sympathomimetic activity. Like other beta blockers, and unlike the anti-glaucoma medication pilocarpine, levobunolol has no effect on accommodation and pupil size. [3] [5]

Pharmacokinetics

Dihydrolevobunolol, the metabolite, which has equal activity to levobunolol Dihydrolevobunolol.svg
Dihydrolevobunolol, the metabolite, which has equal activity to levobunolol

The substance quickly penetrates 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 of six hours and is mainly excreted via the kidney. [2] [3]

Chemistry

Levobunolol is the pure L-enantiomer of bunolol and has more than 60 times the pharmacological activity of D-bunolol. [3] It is used as the hydrochloride, which melts at 209 to 211 °C (408 to 412 °F) and is soluble in water and methanol and slightly soluble in ethanol. [2]

Related Research Articles

<span class="mw-page-title-main">Glaucoma</span> Group of eye diseases

Glaucoma is a group of eye diseases that result in damage to the optic nerve and cause vision loss. The most common type is open-angle glaucoma, in which the drainage angle for fluid within the eye remains open, with less common types including closed-angle glaucoma and normal-tension glaucoma. Open-angle glaucoma develops slowly over time and there is no pain. Peripheral vision may begin to decrease, followed by central vision, resulting in blindness if not treated. Closed-angle glaucoma can present gradually or suddenly. The sudden presentation may involve severe eye pain, blurred vision, mid-dilated pupil, redness of the eye, and nausea. Vision loss from glaucoma, once it has occurred, is permanent. Eyes affected by glaucoma are referred to as being glaucomatous.

<span class="mw-page-title-main">Pilocarpine</span> Medication used to treat glaucoma and dry mouth

Pilocarpine is a medication used to reduce pressure inside the eye and treat dry mouth. As eye drops it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to bring about constriction of the pupil following its dilation. However, due to its side effects it is no longer typically used in the long term management. Onset of effects with the drops is typically within an hour and lasts for up to a day. By mouth it is used for dry mouth as a result of Sjögren syndrome or radiation therapy.

<span class="mw-page-title-main">Aqueous humour</span> Fluid in the anterior segment of the eye

The aqueous humour is a transparent water-like fluid similar to 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 posterior chambers of the eye, and is not to be confused with the vitreous humour, which is located in the space between the lens and the retina, also known as the posterior cavity or vitreous chamber. Blood cannot normally enter the eyeball.

Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery. It is generally administered as an ophthalmic solution.

<span class="mw-page-title-main">Ciliary body</span> Part of the eye

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 body. The ciliary body is part of the uvea, the layer of tissue that delivers oxygen and nutrients to the eye tissues. The ciliary body joins the ora serrata of the choroid to the root of the iris.

<span class="mw-page-title-main">Intraocular pressure</span> Fluid pressure inside the eye

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 to measure pressure in millimeters of mercury (mmHg).

<span class="mw-page-title-main">Trabecular meshwork</span> Area of tissue in the eye

The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber.

<span class="mw-page-title-main">Betaxolol</span> Chemical compound

Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and angina. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronchospasm as timolol may. Betaxolol also shows greater affinity for beta1 receptors than metoprolol. In addition to its effect on the heart, betaxolol reduces the pressure within the eye. This effect is thought to be caused by reducing the production of the liquid within the eye. The precise mechanism of this effect is not known. The reduction in intraocular pressure reduces the risk of damage to the optic nerve and loss of vision in patients with elevated intraocular pressure due to glaucoma.

<span class="mw-page-title-main">Latanoprost</span>

Latanoprost, sold under the brand name Xalatan among others, is a medication used to treat increased pressure inside the eye. This includes ocular hypertension and open angle glaucoma. It is applied as eye drops to the eyes. Onset of effects is usually within four hours, and they last for up to a day.

<span class="mw-page-title-main">Timolol</span> Chemical compound

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 pain due to insufficient blood flow to the heart, to prevent further complications after a heart attack, and to prevent migraines.

<span class="mw-page-title-main">Brimonidine</span> Chemical compound

Brimonidine is a medication used to treat open-angle glaucoma, ocular hypertension, and rosacea. In rosacea it improves the redness. It is used as eye drops or applied to the skin.

<span class="mw-page-title-main">Brinzolamide</span>

Brinzolamide is a carbonic anhydrase inhibitor used to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

<span class="mw-page-title-main">Dorzolamide</span> Chemical compound

Dorzolamide, sold under the brand name Trusopt among others, is a medication used to treat high pressure inside the eye, including in cases of glaucoma. It is used as an eye drop. Effects begin within three hours and last for at least eight hours. It is also available as the combination dorzolamide/timolol.

<span class="mw-page-title-main">Bimatoprost</span> Chemical compound

Bimatoprost, sold under the brand name Lumigan among others, is a medication used to treat high pressure inside the eye including glaucoma. Specifically it is used for open angle glaucoma when other agents are not sufficient. It may also be used to increase the size of the eyelashes. It is used as an eye drop and effects generally occur within four hours.

<span class="mw-page-title-main">Levobetaxolol</span> Chemical compound

Levobetaxolol is a drug used to lower the pressure in the eye in treating conditions such as glaucoma. It is marketed as a 0.25 or 0.5% ophthalmic solution of levobetaxolol hydrochloride under the trade name Betaxon. Levobetaxolol is a beta-adrenergic receptor inhibitor.

<span class="mw-page-title-main">Ibopamine</span> Chemical compound

Ibopamine is a sympathomimetic drug, designed as a prodrug of epinine, used in ophthalmology. It induces mydriasis. It also has been investigated for use in the treatment of congestive heart failure.

Brimonidine/timolol, sold under the brand name Combigan among others, is a fixed-dose combination medication eye drop used for the treatment of glaucoma. It is a combination of brimonidine and timolol.

<span class="mw-page-title-main">Tafluprost</span>

Tafluprost is a prostaglandin analogue. It is used topically to control the progression of open-angle glaucoma and in the management of ocular hypertension, alone or in combination with other medication. It reduces intraocular pressure by increasing the outflow of aqueous fluid from the eyes.

Bimatoprost/timolol, sold under the brand name Ganfort, is a medication for the treatment of certain conditions involving high pressure in the eyes, specifically open angle glaucoma and ocular hypertension. It is available as eye drops.

<span class="mw-page-title-main">Secondary glaucoma</span>

Secondary glaucoma is a collection of progressive optic nerve disorders associated with a rise in intraocular pressure (IOP) which results in the loss of vision. In clinical settings, it is defined as the occurrence of IOP above 21 mmHg requiring the prescription of IOP-managing drugs. It can be broadly divided into two subtypes: secondary open-angle glaucoma and secondary angle-closure glaucoma, depending on the closure of the angle between the cornea and the iris. Principal causes of secondary glaucoma include optic nerve trauma or damage, eye disease, surgery, neovascularization, tumours and use of steroid and sulfa drugs. Risk factors for secondary glaucoma include uveitis, cataract surgery and also intraocular tumours. Common treatments are designed according to the type and the underlying causative condition, in addition to the consequent rise in IOP. These include drug therapy, the use of miotics, surgery or laser therapy.

References

  1. "Archived copy" (PDF). Archived (PDF) from the original on 2022-09-06. Retrieved 2022-09-06.{{cite web}}: CS1 maint: archived copy as title (link)
  2. 1 2 3 4 5 6 7 8 9 Dinnendahl, V; Fricke, U, eds. (2011). Arzneistoff-Profile (in German). Vol. 6 (25 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN   978-3-7741-9846-3.
  3. 1 2 3 4 5 6 Haberfeld, H (ed.). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  4. 1 2 FDA Professional Drug Information on levobunolol.
  5. Mutschler, Ernst (2012). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 781. ISBN   978-3-8047-2898-1.