Chemistry:Timolol

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Short description: Chemical compound


Timolol
Timolol structure.svg
Timolol ball-and-stick.png
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[3])
Onset of action15–30 min[2]
Elimination half-life2.5–5 hours
Duration of action24 hours[2]
ExcretionKidney
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC13H24N4O3S
Molar mass316.42 g·mol−1
3D model (JSmol)
  (verify)

Timolol is a beta blocker medication used either by mouth or as eye drops.[2][4] As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma.[2] 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]

Common side effects with the drops is irritation of the eye.[2] 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.[2] Use is not recommended in those with asthma, uncompensated heart failure, or COPD.[2] It is unclear if use during pregnancy is safe for the baby.[5] Timolol is a non-selective beta blocker.[2]

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.[2][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.[2][13] The mechanism of action of timolol is probably the reduction of the formation of aqueous humor[2] 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]

References

  1. ↑ 1.0 1.1 "Timolol". Drugs.com. https://www.drugs.com/international/timolol.html. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 "Timolol eent". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/timolol-eent.html. 
  3. ↑ "Timolol metabolism in human liver microsomes is mediated principally by CYP2D6". Drug Metabolism and Disposition 35 (7): 1135–1141. July 2007. doi:10.1124/dmd.106.012906. PMID 17431033. 
  4. ↑ 4.0 4.1 4.2 "Timolol Maleate". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/timolol-maleate.html. 
  5. ↑ "Timolol ophthalmic Use During Pregnancy". The American Society of Health-System Pharmacists. https://www.drugs.com/pregnancy/timolol-ophthalmic.html. 
  6. ↑ Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 460. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA460. 
  7. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  8. ↑ "Competitive Generic Therapy Approvals". 29 June 2023. https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals. 
  9. ↑ "The Top 300 of 2020". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  10. ↑ "Timolol - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/Timolol. 
  11. ↑ 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. 27 February 2009. pp. 141–. ISBN 978-1-60327-438-8. https://books.google.com/books?id=Z5YWpjj89NEC&pg=PA141. Retrieved 14 November 2010. 
  12. ↑ "Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery". Pharmacol Rev 70 (2): 197–245. April 2018. doi:10.1124/pr.117.014381. PMID 29487083. 
  13. ↑ 13.0 13.1 "Timolol Ophthalmic". 15 April 2017. https://medlineplus.gov/druginfo/meds/a682043.html. 
  14. ↑ "Glaucoma management: relative value and place in therapy of available drug treatments". Therapeutic Advances in Chronic Disease 5 (1): 30–43. January 2014. doi:10.1177/2040622313511286. PMID 24381726. 
  15. ↑ "Comparison of the nighttime effects of once-daily timolol and latanoprost on intraocular pressure". American Journal of Ophthalmology 138 (3): 389–95. September 2004. doi:10.1016/j.ajo.2004.04.022. PMID 15364220. 
  16. ↑ "Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving latanoprost monotherapy". Ophthalmology 116 (3): 449–54. March 2009. doi:10.1016/j.ophtha.2008.09.054. PMID 19157559. 
  17. ↑ "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. September 2016. doi:10.1016/j.ajo.2016.04.019. PMID 27457257. 
  18. ↑ "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. July 1998. PMID 9697378. 
  19. ↑ "Ganfort 0.3 mg/ml + 5 mg/ml eye drops, solution - Summary of Product Characteristics (SmPC)". 20 February 2020. https://www.medicines.org.uk/emc/product/204/smpc. 
  20. ↑ "Neuroprotection for treatment of glaucoma in adults". The Cochrane Database of Systematic Reviews 1 (1): CD006539. January 2017. doi:10.1002/14651858.CD006539.pub4. PMID 28122126. 
  21. ↑ "Interventions for infantile haemangiomas of the skin". The Cochrane Database of Systematic Reviews 2018 (4): CD006545. April 2018. doi:10.1002/14651858.CD006545.pub3. PMID 29667726. 
  22. ↑ 22.0 22.1 22.2 22.3 "Timolol Maleate tablet". 17 August 2006. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57c62928-63d8-4505-9b9e-c085a3a12c95. 
  23. ↑ "Package leaflet: Information for the user Timolol". https://www.hpra.ie/img/uploaded/swedocuments/PIL-2183359-20032017174542-636256287433370000.pdf. 
  24. ↑ 24.0 24.1 "Betimol- timolol solution". 18 March 2010. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00f62dd1-dad2-4892-8a5d-21e5e54509ce. 
  25. ↑ "Generic Istalol Availability". Drugs.com. https://www.drugs.com/availability/generic-istalol.html. 
  26. ↑ "Istalol". Drugs.com. 1 August 2018. https://www.drugs.com/pro/istalol.html. 

External links



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