Timolol

Last updated

    Timolol
    Timolol structure.svg
    Timolol ball-and-stick.png
    Clinical data
    Trade names Betimol, Blocadren, Istalol, Timoptic, others [1]
    AHFS/Drugs.com Maleate Monograph
    eent Monograph
    MedlinePlus a684029
    License data
    Pregnancy
    category
    • AU:C
    Routes of
    administration         		By mouth, topical (eye drop)
    Drug class Beta blocker
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 60%
    Metabolism Liver (80%, mainly CYP2D6 [2] )
    Onset of action 15–30 min [3]
    Elimination half-life 2.5–5 hours
    Duration of action 24 hours [3]
    Excretion Kidney
    Identifiers
    • (S)-1-(tert-Butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard 100.043.651 OOjs UI icon edit-ltr-progressive.svg
    Chemical and physical data
    Formula C13H24N4O3S
    Molar mass 316.42 g·mol−1
    3D model (JSmol)
    • CC(C)(C)NCC(O)COc1nsnc1N1CCOCC1
    • InChI=1S/C13H24N4O3S/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17/h10,14,18H,4-9H2,1-3H3/t10-/m0/s1 Yes check.svgY
    • Key:BLJRIMJGRPQVNF-JTQLQIEISA-N Yes check.svgY
       (verify)

    Timolol is a beta blocker medication used either by mouth or as eye drops. [3] [4] As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. [3] 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. [4]

    Contents

    Common side effects with the drops is irritation of the eye. [3] Common side effects by mouth include tiredness, slow heart beat, itchiness, and shortness of breath. [4] Other side effects include masking the symptoms of low blood sugar in those with diabetes. [3] Use is not recommended in those with asthma, uncompensated heart failure, or COPD. [3] It is unclear if use during pregnancy is safe for the baby. [5] Timolol is a non-selective beta blocker. [3]

    Timolol was patented in 1968, and came into medical use in 1978. [6] It is on the World Health Organization's List of Essential Medicines. [7] Timolol is available as a generic medication. [3] [8] In 2020, it was the 143rd most commonly prescribed medication in the United States, with more than 4 million prescriptions. [9] [10]

    Medical uses

    By mouth

    In its by mouth or oral form, it is used:

    The combination of timolol and the alpha-1 blocker prazosin has sedative effects. [12]

    Eye drops

    In its eye drop form it is used to treat open-angle and, occasionally, secondary glaucoma. [3] [13] The mechanism of action of timolol is probably the reduction of the formation of aqueous humor [3] in the ciliary body in the eye. It was the first beta blocker approved for topical use in treatment of glaucoma in the United States (1978). [14] When used by itself, it depresses intraocular pressure (IOP) 18–34% below baseline within first few treatments. However, there are short-term escape and long-term drift effects in some people. That is, tolerance develops. It may reduce the extent of the daytime IOP curve up to 50%. The IOP is higher during sleep. Efficacy of timolol in lowering IOP during the sleep period may be limited. [15] [16] [17] It is a 5–10× more potent beta blocker than propranolol. Timolol is light-sensitive; it is usually preserved with 0.01% benzalkonium chloride (BAC), but also comes BAC-free. It can also be used in combination with pilocarpine, carbonic anhydrase inhibitors [18] or prostaglandin analogs. [19]

    A Cochrane review compared the effect of timolol versus brimonidine in slowing the progression of open angle glaucoma in adults but found insufficient evidence to come to conclusions. [20]

    On the skin

    In its gel form it is used on the skin to treat infantile hemangiomas. [21]

    Contraindications

    The medication should not be taken by individuals with: [22]

    Side effects

    The most serious possible side effects include cardiac arrhythmias and severe bronchospasms. [22] Timolol can also lead to fainting, congestive heart failure, depression, confusion, worsening of Raynaud's syndrome and impotence. [22]

    Side effects when given in the eye include: burning sensation, eye redness, superficial punctate keratopathy, corneal numbness. [24] [13]

    Formulations

    It is available in tablet and liquid formulations. [22] [24]

    For ophthalmic use, timolol is also available combined:

    Brand names

    Timolol is marketed under many trade names worldwide. [1] Timolol eye drops are marketed under the brand name Istalol among others. [25] [26]

    Related Research Articles

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

    Glaucoma is a group of eye diseases that lead to damage of the optic nerve, which is important for transmitting visual information from the eye to the brain. This damage is often caused by increased pressure within the eye, known as intraocular pressure (IOP) and may cause vision loss if left untreated. The word glaucoma originated from the Greek word ΓλαύV̇ξ (glaukos), which means "to glow". Glaucoma has been called the "silent thief of sight" because the loss of vision usually occurs slowly over a long period of time. It is associated with old age, a family history of glaucoma, and certain medical conditions or medications.

    <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 an eye drop it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to constrict the pupil after dilation. However, due to its side effects it is no longer typically used for 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">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">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> Chemical compound

    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.

    Ocular hypertension is the presence of elevated fluid pressure inside the eye, usually with no optic nerve damage or visual field loss.

    Dorzolamide/timolol, sold under the brand name Cosopt among others, is a medication used to treat high pressure inside the eye including glaucoma. It is a combination of dorzolamide hydrochloride and timolol maleate. It may be used when a beta blocker, like timolol, is not sufficient alone. It is used as an eye drop.

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

    Brimonidine is an α2 agonist 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">Apraclonidine</span> Chemical compound

    Apraclonidine (INN), also known under the brand name Iopidine, is a sympathomimetic used in glaucoma therapy. It is an α2 adrenergic receptor agonist and a weak α1 adrenergic receptor agonist.

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

    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.

    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> Chemical compound

    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.

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

    Netarsudil, sold under the brand name Rhopressa among others, is a medication for the treatment of glaucoma. In the United States, in December 2017, the Food and Drug Administration (FDA) approved a 0.02% ophthalmic solution for the lowering of elevated intraocular pressure in people with open-angle glaucoma or ocular hypertension. The European Medicines Agency approved it in 2019 for the same uses under the brand name Rhokiinsa.

    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.

    Netarsudil/latanoprost, sold under the brand name Rocklatan among others, is a fixed-dose combination medication use to treat elevated intraocular pressure (IOP) in people with open-angle glaucoma or ocular hypertension. It contains netarsudil mesylate and latanoprost. It is applied as eye drops to the eyes.

    Brinzolamide/brimonidine, sold under the brand name Simbrinza, is a fixed-dose combination medication used to reduce intra-ocular pressure in adults with ocular hypertension or in those with an eye condition known as open-angle glaucoma. It contains brinzolamide and brimonidine tartrate. It is used as an eye drop.

    Travoprost/timolol, sold under the brand name Duotrav among others, is a fixed-dose combination medication used for the treatment of glaucoma. It contains travoprost and timolol maleate.

    References

    1. 1 2 "Timolol". Drugs.com. Archived from the original on 7 March 2016. Retrieved 28 December 2016.
    2. ↑ Volotinen M, Turpeinen M, Tolonen A, Uusitalo J, Mäenpää J, Pelkonen O (July 2007). "Timolol metabolism in human liver microsomes is mediated principally by CYP2D6". Drug Metabolism and Disposition. 35 (7): 1135–1141. doi:10.1124/dmd.106.012906. PMID   17431033. S2CID   794764.
    3. 1 2 3 4 5 6 7 8 9 10 11 "Timolol eent". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 8 December 2016.
    4. 1 2 3 "Timolol Maleate". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 8 December 2016.
    5. ↑ "Timolol ophthalmic Use During Pregnancy". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 28 December 2016.
    6. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 460. ISBN   9783527607495. Archived from the original on 28 December 2016.
    7. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    8. ↑ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.
    9. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
    10. ↑ "Timolol - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
    11. ↑ Marcus DA, Bain PA (27 February 2009). Effective Migraine Treatment in Pregnant and Lactating Women: A Practical Guide. シュプリンガー・ジャパン株式会社. pp. 141–. ISBN   978-1-60327-438-8. Archived from the original on 5 November 2017. Retrieved 14 November 2010.
    12. ↑ Atkin T, Comai S, Gobbi G (April 2018). "Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery". Pharmacol Rev. 70 (2): 197–245. doi: 10.1124/pr.117.014381 . PMID   29487083. S2CID   3578916.
    13. 1 2 "Timolol Ophthalmic". MedlinePlus. 15 April 2017. Retrieved 31 December 2019.
    14. ↑ Sambhara D, Aref AA (January 2014). "Glaucoma management: relative value and place in therapy of available drug treatments". Therapeutic Advances in Chronic Disease. 5 (1): 30–43. doi:10.1177/2040622313511286. PMC   3871276 . PMID   24381726.
    15. ↑ Liu JH, Kripke DF, Weinreb RN (September 2004). "Comparison of the nighttime effects of once-daily timolol and latanoprost on intraocular pressure". American Journal of Ophthalmology. 138 (3): 389–95. doi:10.1016/j.ajo.2004.04.022. PMID   15364220.
    16. ↑ Liu JH, Medeiros FA, Slight JR, Weinreb RN (March 2009). "Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving latanoprost monotherapy". Ophthalmology. 116 (3): 449–54. doi:10.1016/j.ophtha.2008.09.054. PMID   19157559.
    17. ↑ Liu JH, Slight JR, Vittitow JL, Scassellati Sforzolini B, Weinreb RN (September 2016). "Efficacy of Latanoprostene Bunod 0.024% Compared With Timolol 0.5% in Lowering Intraocular Pressure Over 24 Hours". American Journal of Ophthalmology. 169: 249–257. doi: 10.1016/j.ajo.2016.04.019 . PMID   27457257.
    18. ↑ Strohmaier K, Snyder E, Adamsons I (July 1998). "A multicenter study comparing dorzolamide and pilocarpine as adjunctive therapy to timolol: patient preference and impact on daily life". Journal of the American Optometric Association. 69 (7): 441–51. PMID   9697378.
    19. ↑ "Ganfort 0.3 mg/ml + 5 mg/ml eye drops, solution - Summary of Product Characteristics (SmPC)". (emc). 20 February 2020. Retrieved 1 March 2020.
    20. ↑ Sena DF, Lindsley K (January 2017). "Neuroprotection for treatment of glaucoma in adults". The Cochrane Database of Systematic Reviews. 1 (1): CD006539. doi:10.1002/14651858.CD006539.pub4. PMC   5370094 . PMID   28122126.
    21. ↑ Novoa M, Baselga E, Beltran S, Giraldo L, Shahbaz A, Pardo-Hernandez H, Arevalo-Rodriguez I (April 2018). "Interventions for infantile haemangiomas of the skin". The Cochrane Database of Systematic Reviews. 2018 (4): CD006545. doi:10.1002/14651858.CD006545.pub3. PMC   6513200 . PMID   29667726.
    22. 1 2 3 4 "Timolol Maleate tablet". DailyMed. 17 August 2006. Retrieved 1 December 2019.
    23. ↑ "Package leaflet: Information for the user Timolol" (PDF). hpra.ie.
    24. 1 2 "Betimol- timolol solution". DailyMed. 18 March 2010. Retrieved 1 December 2019.
    25. ↑ "Generic Istalol Availability". Drugs.com . Retrieved 20 June 2019.
    26. ↑ "Istalol". Drugs.com. 1 August 2018. Retrieved 19 July 2019.
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