Timolol_Maleate: profile and news

Study Demonstrates Benefits of Combination Treatment for Glaucoma May 11, 2006
...clinically significant additional reduction in intraocular pressure (IOP) when treated with Cosopt® (dorzolamide hydrochloride/timolol maleate) alone or when ... - DG News

Other information

Indication
For the treatment of hypertension, angina pectoris, cardiac arrhythmias, migraine and for the reduction of mortality following myocardial infarction. Ophthalmic solutions of timolol are used in the treatment of glaucoma to reduce intraocular pressure.

Pharmacology
Similar to propranolol and nadolol, timolol is a nonselective, beta-adrenergic receptor antagonist. Timolol does not demonstrate appreciable intrinsic sympathomimetic or membrane-stabilizing activities but possesses a relatively high degree of lipid solubility and is subject to first-pass metabolism by the liver.

Mechanism Of Action
Like propranolol and nadolol, timolol competes with adrenergic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle and beta(2)-receptors in the bronchial and vascular smooth muscle. Beta(1)-receptor blockade results in a decrease in resting and exercise heart rate and cardiac output, a decrease in both systolic and diastolic blood pressure, and, possibly, a reduction in reflex orthostatic hypotension. Beta(2)-blockade results in an increase in peripheral vascular resistance. The exact mechanism whereby timolol reduces ocular pressure is still not known. The most likely action is by decreasing the secretion of aqueous humor.

Drug Category
Antihypertensive Agents; Antiarrhythmic Agents; EENT Drugs; ATC:C07AA06; ATC:S01ED01

Brand Names/Synonyms
Apo-Timol; Apo-Timop; Aquanil; Betim; Betimol; Blocadren; HSDB 6533; Istalol; Novo-Timol; Proflax; Temserin; Tenopt; Tim-Ak; Timacar; Timacor; Timolol; Timolol Base; Timolol Maleate; Timololum [Inn-Latin]; Timopic; Timoptic; Timoptic in Ocudose; Timoptic-Xe; Timoptol

Dosage Forms
DROPS; LIQUID; SOLUTION; SOLUTION (LONG-ACTING); TABLET

Absorption
Bioavailability is about 60%

Interactions
-->Interactions for Timolol:

Beta-adrenergic blocking agents: Patients who are receiving a beta-adrenergic blocking agent orally and Timolol GFS should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. Patients should not usually receive two topical ophthalmic beta-adrenergic blocking agents concurrently.

Calcium antagonists: Caution should be used in the co-administration of beta-adrenergic blocking agents, such as Timolol GFS, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, or hypotension. In patients with impaired cardiac function, co-administration should be avoided.

ENDOCRINE

Masked symptoms of hypoglycemia in diabetic patients. SPECIAL SENSES

Signs and symptoms of ocular irritation including blepharitis, keratitis, and dry eyes; ptosis; decreased corneal sensitivity; cystoid macular edema; visual disturbances including refractive changes and diplopia; pseudopemphigoid; tinnitus and choroidal detachment following filtration surgery.

UROGENITAL

Retroperitoneal fibrosis, decreased libido, impotence and Peyronieís disease.

The following additional adverse effects have been reported in clinical experience with ORAL timolol maleate or other ORAL beta-blocking agents and may be considered potential effects of ophthalmic timolol maleate: Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Body as a Whole: Extremity pain, decreased exercise tolerance, weight loss; Cardiovascular: Worsening of arterial insufficiency, vasodilatation; Digestive: Gastrointestinal pain, hepatomegaly, vomiting, mesenteric arterial thrombosis, ischemic colitis; Hematologic: Nonthrombocytopenic purpura, thrombocytopenic purpura, agranulocytosis; Endocrine: Hyperglycemia, hypoglycemia; Skin: Pruritus, skin irritation, increased pigmentation, sweating; Musculoskeletal: Arthralgia; Nervous System/Psychiatric: Vertigo, local weakness, diminished concentration, reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometric tests; Respiratory: Rales, bronchial obstruction; Urogenital: Urination difficulties.

Chemical IUPAC Name
1-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]-3-tert-butylamino-propan-2-ol

Chemical Formula
C13H24N4O3S

Half Life
2.5-5 hours

Drug Type
Approved Drug

# Accession No
APRD00229

CAS Registry Number
26839-75-8