Timolol

Timolol maleate is a non-selective beta-adrenergic receptor blocker.

Uses

In its oral form (Blocadren), it is used:

• to treat high blood pressure
• to prevent heart attacks
• to prevent migraine headaches^[1]

In its ophthalmic form (brand names Timoptol in Italy; Timoptic), it is used to treat open-angle and occasionally secondary glaucoma by reducing aqueous humour production through blockage of the beta receptors on the ciliary epithelium. The pharmacological mechanism by which it actually does this is still unknown. First beta-blocker approved for topical use in treatment of glaucoma in the USA (1978). With monotherapy, depresses IOP 18-34% below baseline within first few treatments. However, there are short-term escape and long-term drift effects in some patients. That is, tolerance develops. May reduce extent of diurnal IOP curve up to 50%. IOP higher during sleep. 5-10x more potent beta-blocker than propranolol. Light sensitive; preserved with 0.01% benzalkonium Cl (and also comes BAC free). Can also be used in adjunctive therapy with pilocarpine or CAIs.

Side effects

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

Usual dosage

• Children and Adults: Ophthalmic: Initial: 0.25% solution, instill 1 drop twice daily; increase to 0.5% solution if response not adequate; decrease to 1 drop/day if *controlled; do not exceed 2 drops twice daily of 0.5% solution Adults: Oral:
• Hypertension: Initial: 10 mg twice daily, increase gradually every 14 days, usual dosage: 20–40 mg/day in 2 divided doses; maximum: 60 mg/day
• Prevention of myocardial infarction: 10 mg twice daily initiated within 1–6 weeks after infarction
• Migraine headache: Initial: 10 mg twice daily, increase to maximum of 30 mg/day

Formulations

• Gel-forming solution, ophthalmic, as maleate (Timoptic-XE): 0.25% (2.5 mL, 5 mL); 0.5% (2.5 mL, 5 mL)
• Solution, ophthalmic, as hemihydrate (Betimol): 0.25% (5 mL, 10 mL, 15 mL); 0.5% (5 mL, 10 mL, 15 mL) [contains benzalkonium chloride]
• Solution, ophthalmic, as maleate: 0.25% (5 mL, 10 mL, 15 mL); 0.5% (5 mL, 10 mL, 15 mL) [contains benzalkonium chloride]
• Timoptic: 0.25% (5 mL, 10 mL); 0.5% (5 mL, 10 mL) [contains benzalkonium chloride]
• Solution, ophthalmic, as maleate [preservative free] (Timoptic OcuDose): 0.25% (0.2 mL);0.5% (0.2 mL) [single use]
• Tablet, as maleate (Blocadren): 5 mg, 10 mg, 20 mg

For ophthalmic use, timolol is also available combined with other medications:

• Combigan - timolol and brimonidine
• Cosopt - timolol maleate and dorzolamide hydrochloride
• DuoTrav - timolol and travoprost
• Xalacom (Pfizer) - timolol and latanoprost

Brand names

• In Canada: Apo-Timol, Apo-Timop, Gen-Timolol, Nu-Timolol, Phoxal-timolol, PMS-Timolol, Tim-AK, Timoptic, Timoptic-XE.
• In the United States: Betimol, Blocadren, Istalol, Timoptic, Timoptic-XE, Timoptic OcuDose.

Chemical synthesis

References

External links

• http://dx.doi.org/10.1021/jo00881a011