Active ingredient: Timolol - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antihypertensive Agents
• Anti-Arrhythmia Agents
• Adrenergic beta-Antagonists

Dosage Forms

• Drops
• Liquid
• Solution
• Solution (long-acting)
• Tablet

Brands / Synonyms

Apo-Timol; Apo-Timop; Aquanil; Betim; Betimol; Blocadren; Combigan; Cosopt; Istalol; Novo-Timol; Proflax; Temserin; Tenopt; Tim-AK; Timacar; Timacor; Timolide; Timololum [INN-Latin]; Timopic; Timoptic; Timoptic in Ocudose; Timoptic-XE; Timoptol

Indications

In its oral form it is used to treat high blood pressure and prevent heart attacks, and occasionally to prevent migraine headaches. In its opthalmic form it is used to treat open-angle and occasionally secondary glaucoma.

Pharmacology

Similar to propranolol and nadolol, timolol is a non-selective, beta-adrenergic receptor antagonist. Timolol does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity, but does possess a relatively high degree of lipid solubility. Timolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage.

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.

Absorption

Bioavailability is about 60%

Toxicity

LD₅₀=1190 mg/kg (oral, mice), LD₅₀=900 mg/kg (oral, rat). Symptoms of overdose include drowsiness, vertigo, headache, and atriventricular block.

Biotrnasformation / Drug Metabolism

Primarily hepatic (80%) via the cytochrome P450 2D6 isoenzyme.

Contraindications

Timolol GFS is contraindicated in patients with (1) bronchial asthma; (2) a history of bronchial asthma; (3) severe chronic obstructive pulmonary disease; (4) sinus bradycardia; (5) second or third degree atrioventricular block; (6) overt cardiac failure; (7) cardiogenic shock; or (8) hypersensitivity to any component of this product.

Drug Interactions

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.