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Metoprolol: The Benefit of the Drug and the Indication and the Action of Drug

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Many therapeutic agents can be used for the pharmacologic management of hypertension. The general recommendation established by the Seventh Report of the Prevention, Detection, Evaluation, and Treatment of the Joint National Committee on High Blood Pressure (JNC 7) is to initiate a thiazide-type diuretic initially for stage 1 hypertensive patients without compelling indications for other therapies.

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Pharmacodynamics refers to the relationship between drug concentration at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects. The effect of a drug present at the site of action is determined by that drug’s binding with a receptor. Receptors may be present on neurons in the central nervous system (i.e., opiate receptors) to depress pain sensation, on cardiac muscle to affect the intensity of contraction, or even within bacteria to disrupt maintenance of the bacterial cell wall. For most drugs, the concentration at the site of the receptor determines the intensity of a drug’s effect

However, other factors affect drug response as well. Density of receptors on the cell surface, the mechanism by which a signal is transmitted into the cell by second messengers (substances within the cell), or regulatory factors that control gene translation and protein production may influence drug effect.

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Metoprolol is FDA-approved for the treatment of angina, heart failure, myocardial infarction, atrial fibrillation/flutter, and hypertension. Off-label uses include supraventricular tachycardia and thyroid storm (Brogden RN, 1977). Both oral and intravenous preparations are available. There are immediate and extended-release preparations available orally. There is controversy regarding the selection of beta-blockers in the management of the above conditions. There also is conflicting evidence regarding the optimal selection of a particular beta-blocker in the treatment of each specific disease. The role of beta-blockers as initial therapy for hypertension, particularly in the absence of compelling indications, has been questioned. Several randomized trials in the 1980s showed a mortality benefit for beta-blockers in acute myocardial infarction. The Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial specifically showed a benefit of metoprolol over diuretics regarding sudden cardiac death as well as myocardial infarction. A large randomized trial of over 50,000 patients in the 1990s showed metoprolol to reduce mortality and re-infarction when used chronically after myocardial infarction. Beta-blockers have demonstrated prognostic benefit and reduce mortality in the treatment of chronic heart failure. The carvedilol or metoprolol European trial (COMET) enrolled patients with stable heart failure and compared each drug head-to-head. Carvedilol was associated with a statistically significantly lower risk of all-cause death (Freemantle N, Cleland J, 1999). However, recent trials have had conflicting evidence on whether selective beta-1 blockers such as metoprolol have any benefit over other beta-blockers like carvedilol.

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In the end, the invention of beta (β)-blockers culminated in a new era in the treatment of cardiovascular diseases (CD), and changed the course of pharmacology research for years to come. Since the introduction of propranolol into clinical practice in 1964, β-blockers enjoyed a special place in the clinicians’ armamentarium against CDs, especially for patients with ischemic heart diseases, and are still one of the most extensively used therapeutic drugs in both cardiac and non-cardiac ailments

Current uses of β-blockers in CDs include ischemic heart diseases, hypertension, cardiac arrhythmias, and heart failure.

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Freemantle N, Cleland J, Young P, Mason J, Harrison J. beta Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999 Jun 26;318(7200):1730-7.

Remme WJ, Cleland JG, Erhardt L, Spark P, Torp-Pedersen C, Metra M, Komajda M, Moullet C, Lukas MA, Poole-Wilson P, Di Lenarda A, Swedberg K. Effect of carvedilol and metoprolol on the mode of death in patients with heart failure. Eur. J. Heart Fail. 2007 Nov;9(11):1128-35.

Brogden RN, Heel RC, Speight TM, Avery GS. Metoprolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Drugs. 1977

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