| Indication | 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. |
| Pharmacodynamics | 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% |
| Volume of distribution | Not Available |
| Protein binding | ~10% |
| Metabolism | Primarily hepatic (80%) via the cytochrome P450 2D6 isoenzyme. |
| Route of elimination | Timolol and its metabolites are primarily excreted in the urine. |
| Half life | 2.5-5 hours |
| Clearance | Not Available |
| Toxicity | LD50=1190 mg/kg (oral, mice), LD50=900 mg/kg (oral, rat). Symptoms of overdose include drowsiness, vertigo, headache, and atriventricular block. |