Timolol MOA assignment PDF

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Timolol mechanism of action...

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Drug Mechanism of Action Assignments Rebecca Gotthelf Professor Mirrione Timolol Timolol, or usually seen as Timolol maleate, can be taken orally or ophthamically. Focusing on the oral route, Timolol is used orally to treat a variety of different ailments, such as hypertension, secondary prevention of myocardial infarction, and occasionally atrial fibrillation. It is a non-selective, reversible, beta-adrenergic competitive antagonist, with its use as an antihypertensive betablocker. It 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. Sympathomimetic drug, or adrenergic drugs are stimulant compounds that mimic the effects of endogenous agonists of the sympathetic nervous system. Timolol acts on both beta one and beta two receptors and competes with adrenergic neurotransmitters such as catecholamines for these receptors. Timolol competes at the beta one adrenergic receptor in the heart and vascular smooth muscles to ultimately decrease heart rate and cardiac output, and decrease both systolic and diastolic blood pressure. At the beta two receptors, it competes in both the bronchial and vascular smooth muscle to increase peripheral vascular resistance. Agonists of beta one receptors typically increase cardiac output, and the rate of depolarization of sinoatrial and atrioventricular nodes, which increases heart rate an antagonist, such as Timolol, would do the opposite, decreasing the heart rate and cardiac output, ultimately decreasing blood pressure. Side effects of the beta two interaction of Timolol on bronchial tubes is bronchoconstriction. An agonist’s effect on the bronchial tubes would result in relaxation of the bronchioles, however since Timolol is an antagonist it would result in the constriction. The reason that timolol increases peripheral vascular resistance is that due to the decreased cardiac output and aortic pressure, it triggers a reflex increase in sympathetic tone. The bioavailabilty of Timolol is approximately 50% as an oral dose. Timolol undergoes extensive first pass metabolism so only 50% of the unchanged drug reaches systemic circulaltion. It is primarily metabolized in the liver by cytochrome P450 2D6 isoenzymes, and excreted in the urine. The onset of activity is within approximately 30 minutes of either ingestion or application with peak plasma concentration within around one to two hours. It has about a 10%-60% affinity to bind to plasma protein. It has a half-life of 3 to 4 hours. Although this has mainly focused on the oral route of timolol, it is also available in eye drops, and although the mechanism of action is not specifically known, it is thought to reduce the intra-ocular pressure due to possibly decreasing the aqueous humor production through a reduction of blood flow to the ciliary processes and cAMP synthesis.

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