Timolol

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]

    Timolol
    Clinical data
    Trade namesBetimol, Blocadren, Istalol, Timoptic, others[1]
    AHFS/Drugs.comMaleate Monograph
    eent Monograph
    MedlinePlusa684029
    License data
    Pregnancy
    category
    • AU: C
    Routes of
    administration    		By mouth, topical (eye drop)
    Drug classBeta blocker
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability60%
    MetabolismLiver (80%, mainly CYP2D6[2])
    Onset of action15–30 min[3]
    Elimination half-life2.5–5 hours
    Duration of action24 hours[3]
    ExcretionKidney
    Identifiers
    IUPAC name
    • (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 InfoCard100.043.651
    Chemical and physical data
    FormulaC13H24N4O3S
    Molar mass316.42 g·mol−1
    3D model (JSmol)
    SMILES
    • CC(C)(C)NCC(O)COc1nsnc1N1CCOCC1
    InChI
    • 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 Y
    • Key:BLJRIMJGRPQVNF-JTQLQIEISA-N Y
      (verify)

    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] In 2020, it was the 14rd3 most commonly prescribed medication in the United States, with more than 4 million prescriptions.[8][9]

    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.[11]

    Eye drops

    In its eye drop form it is used to treat open-angle and, occasionally, secondary glaucoma.[3][12] 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).[13] 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 diurnal IOP curve up to 50%. The IOP is higher during sleep. Efficacy of timolol in lowering IOP during the sleep period may be limited.[14][15][16] It is a 5–10× more potent β-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[17] or prostaglandin analogs.[18]

    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.[19]

    On the skin

    In its gel form it is used on the skin to treat infantile hemangiomas.[20]

    Contraindications

    The medication should not be taken by individuals with:[21]

    Side effects

    The most serious possible side effects include cardiac arrhythmias and severe bronchospasms.[21] Timolol can also lead to fainting, congestive heart failure, depression, confusion, worsening of Raynaud's syndrome and impotence.[21]

    Side effects when given in the eye include: burning sensation, eye redness, superficial punctate keratopathy, corneal numbness.[23][12]

    Formulations

    It is available in tablet and liquid formulations.[21][23]

    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.[24][25]

    References
    1. "Timolol". Drugs.com. Archived from the original on 7 March 2016. Retrieved 28 December 2016.
    2. Volotinen, Marjo; Turpeinen, Miia; Tolonen, Ari; Uusitalo, Jouko; Mäenpää, Jukka; Pelkonen, Olavi (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. "Timolol eent". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 8 December 2016.
    4. "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. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
    9. "Timolol - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
    10. 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.
    11. 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.
    12. "Timolol Ophthalmic". MedlinePlus. 15 April 2017. Retrieved 31 December 2019.
    13. 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.
    14. Liu JH, Kripke DF, Weinreb RN (September 2004). "Comparison of the nocturnal 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.
    15. 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.
    16. 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.
    17. 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.
    18. "Ganfort 0.3 mg/ml + 5 mg/ml eye drops, solution - Summary of Product Characteristics (SmPC)". (emc). 20 February 2020. Retrieved 1 March 2020.
    19. 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.
    20. 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.
    21. "Timolol Maleate tablet". DailyMed. 17 August 2006. Retrieved 1 December 2019.
    22. "Package leaflet: Information for the user Timolol" (PDF). hpra.ie.
    23. "Betimol- timolol solution". DailyMed. 18 March 2010. Retrieved 1 December 2019.
    24. "Generic Istalol Availability". Drugs.com. Retrieved 20 June 2019.
    25. "Istalol". Drugs.com. 1 August 2018. Retrieved 19 July 2019.
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