Metoprolol

Abstract

During the intervening years since metoprolol was first reviewed in the Journal (1977), it has become widely used in the treatment of mild to moderate hypertension and angina pectoris. Although much data have accumulated, its precise mechanisms of action in these diseases remain largely uncertain. Optimum treatment of hypertension and angina pectoris with metoprolol is achieved through dose titration within the therapeutic range. It has been clearly demonstrated that metoprolol is at least as effective as other beta-blockers, diuretics and certain calcium antagonists in the majority of patients. Although a twice daily dosage regimen is normally used, satisfactory control can be maintained in many patients with single daily doses of conventional or, more frequently, slow release formulations. Addition of a diuretic may improve the overall response rate in hypertension. Several controlled trials have studied the effects of metoprolol administered during the acute phase and after myocardial infarction. In early intervention trials a reduction in total mortality was achieved in one moderately large trial of prolonged treatment, but in another, which excluded patients already being treated with beta-blockers or certain calcium antagonists and where treatment was only short term, mortality was significantly reduced only in 'high risk' patients. Overall results with metoprolol have not demonstrated that early intervention treatment in all patients produces clinically important improvement in short term mortality. Thus, the use of metoprolol during the early stages of myocardial infarction is controversial, largely because of the requirement to treat all patients to save a small number at 'high risk'. This blanket coverage approach to treatment may be more justified during the post-infarction follow-up phase since it has been shown that metoprolol slightly, but significantly, reduces the mortality rate for periods of up to 3 years. Metoprolol is generally well tolerated and its beta 1-selectivity may facilitate its administration to certain patients (e.g. asthmatics and diabetics) in whom non-selective beta-blockers are contraindicated. Temporary fatigue, dizziness and headache are among the most frequently reported side effects. After a decade of use, metoprolol is well established as a first choice drug in mild to moderate hypertension and stable angina, and is beneficial in post-infarction patients. Further study is needed in less well established areas of treatment such as cardiac arrhythmias, idiopathic dilated cardiomyopathy and hypertensive cardiomegaly.

Distribution of metoprolol, tramadol, and midazolam in human autopsy material

“…After extensive hepatic metabolism via cytochrome P450 (CYP2D6) metoprolol is excreted primarily as inactive metabolites, about 95% of a dose is recovered in the urine within 72 h (approximately 3% as unchanged drug). Total body clearance ranges between 43.2 and 92.4 L/h and the elimination half-life is usually 3-4 h [1,2,[27][28][29]. In the seven discovered cases intoxication with metoprolol could be excluded.…”

“…Blockade of the ␤1 receptor reduces heart rate, myocardial contractility and cardiac output. Metoprolol reduces plasma renin activity [1,2]. Numerous causes with metoprolol intoxication have been published.…”

The solid-state structure of the β-blocker metoprolol: a combined experimental and in silico investigation

“…Metoprolol, or (RS)-1-isopropylamino-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol (see a in Scheme 1), is a cardioselective 1 -adrenergic blocking agent that has numerous medical applications, such as the treatment of acute myocardial infarction, heart failure, angina pectoris and hypertension (Benfield et al, 1986;Brogden et al, 1977). The drug is usually manufactured as a racemic mixture, notwithstanding the fact that the 1 -blocking activity resides in the S enatiomer (Dasbiswas et al, 2008).…”

CNS‐related performance and haemodynamics of metoprolol‐Oros and propranolol after single and 3 days dosing in healthy volunteers.

“…Although there has been evidence for a reduction of side-effects related to peripheral 1B-adrenoceptor blockade such as exercise induced fatigue (Blomqvist et al, 1988;Dimenas et al, 1990a) and bronchoconstriction (Lofdahl et al, 1988), there have been no indications of significant reductions in CNSrelated side effects (Benfield et al, 1986;Dimenas & Dahlof, 1990). However, studies thus far have focused on subjective tolerability of sustained release ,B-adrenoceptor blockers only (Dimenas etal., 1990a, b;Houtzagers et al, 1988 (Dimsdale et al, 1989).…”