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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects.
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PMID:Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. 1 92

The wide variety of antihypertensive agents now available allows considerable flexibility in the pharmacologic management of hypertension. The newly available alpha- and beta-adrenergic blocking agents have added considerably to this flexibility. Their safety and efficacy insure that they will find increasing use in the treatment of hypertension. The new postsynaptic alpha-receptor blocker prazosin, is generally free of the side effects that precluded the use of alpha-blockers which affected both pre- and postsynaptic receptors. Is is moderately effective and, excepting the problem of "first-dose" hypotension, it is usually well tolerated. Labetalol, a compound possessing both alpha- and beta-receptor blocking properties, has been found to be effective both as an oral therapy for chronic hypertension and as an intravenous agent in treating hypertensive crisis. Further experience with labetolol will determine its safety and efficacy for the long-term management of hypertension. Although the usefulness of beta-adrenergic receptor blocking agents in hypertension is unquestionable, the mechanism by which they lower the blood pressure remains in question. Most of our experience has been with propranolol, but other beta-blockers, now used in England and Europe, are likely to become available in the United States. As of January, 1979 only metoprolol has been added to propranolol as approved beta-blockers for the treatment of hypertension. General guidelines for the use of propranolol are given in Table 6. Metoprolol will likely find increasing use since it seems to work as well as propranolol and probably causes fewer side effects. Nevertheless, the experiences with one beta-blocker, both good and bad, cannot be interpolated to another beta-blocker since there are obvious and subtle differences in their actions. Patients doing well on propranolol therapy should continue to receive that drug; patients being started on a beta-blocker therapy can be given the choice of metoprolol and, in the near future, other beta-blockers as well. Beyond their efficacy and freedom from side effects in about 80% of patients, beta-blockers may offer a special advantage in protecting from coronary heart disease. Such protection has been suggested in limited trials but needs further documentation. In the meantime, the known advantages of beta-blockers ensure their increasing use in the treatment of hypertension. Regardless of which alpha- or beta-blocker is chosen, a diuretic should be used concomitantly to enhance and preserve the effectiveness of the adrenergic blocker.
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PMID:Alpha- and beta-receptor blocking drugs in the treatment of hypertension. 4 Jul 55

Metoprolol is a beta1-selective adrenoceptor blocking drug. In hypertension, its duration of effect is longer than expected from its half-life and it is suitable for twice daily administration. There is some evidence that once daily administration may be possible in treating hypertension. It is similar in efficacy to other beta-adrenoceptor blocking drugs in angina pectoris and essential hypertension, when given in equiactive beta-blocking dosages. Metoprolol is well tolerated and side-effects have not proved a problem. It has some pharmacodynamic and pharmacokinetic differences from other beta-adrenoceptor blocking drugs and may prove useful in cases where these differences are shown to be clinically important.
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PMID:Metoprolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. 20 41

In a model system the influence of mental stress on blood pressure and heart rate was studied in normal persons and in patients with hypertension (WHO grade III). Metoprolol was employed to investigate the preventive effect of beta-adrenergic blockade on the response to stress. In all groups blood pressure increased significantly during mental stress. The effect was not inhibited by metoprolol. The rise in heart rate, however, was depressed by beta-blockade. Reaction time, opticomotor coordination and concentration ability were studied as parameters of vigilance, but no significant difference between the metoprolol and control groups were observed. Thus, metoprolol only influenced the heart rate in mental stress and it did not affect vigilance.
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PMID:Beta-adrenergic blockade in stress protection. Limited effect of metoprolol in psychological stress reaction. 36 94

In 19 patients with arterial hypertension the hemodynamics were determined with a Swan-Ganz-thermodilution catheter at rest and during supine ergometer exercise before and after 5 mg intravenous Propranolol (P) (10 pats.) respectively 10 mg of intravenous Metoprolol (9 pats.). During exercise, P caused a significantly higher increase in pulmonary capillary wedge pressure (PCP) (15.0 +/- 4.0 to 25.3 +/- 4.0 mm Hg), than M (10.9 +/- 4.8 to 17.4 +/- 5.5 mmHg) (p less than 0.025). There was a uniform reduction of the cardiac output (CO), after P and M. P caused a reduction of the CO by a decrease in heart rate and stroke volume, M through a significantly greater decrease in heart rate (p less than 0.0005), without a change in stroke volume (p less than 0.05). The changes in PCP and stroke volume give evidence of a more negative inotropic effect of P compared to M.
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PMID:[Hemodynamic changes in patients with arterial hypertension after beta-receptor blockade with propranolol and metoprolol (author's transl)]. 73 94

1. A double-blind cross-over evaluation of the anti-hypertensive effect of metoprolol vs placebo was carried out in a series of twenty-three patients with mild or moderate essential hypertension who were receiving 25 mg of chlorthalidone daily as their basic treatment. An individually determined dose of metoprolol (75-300 mg) was used. 2. Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions. 3. During the double-blind cross-over study mild side effects were more common at the beginning of metoprolol/chlorthalidone treatment than during placebo/chlorthalidone, but these tended to diminish or disappear with time. 4. Metoprolol in combination with chlorathalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in patients not responding to chlorthalidone alone.
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PMID:A controlled study on the anti-hypertensive effect of a new beta-adrenoreceptor-blocking drug, metoprolol, in combination with chlorthalidone. 79 61

Metoprolol, a cardioselective beta-blocking agent, has been given orally to 12 geriatric patients with moderate hypertension. Drug levels of metoprolol as well as the effect of the drug on resting heart rate and BP were studied. Metoprolol was given in a dose of 20 mg, and 8 of the 12 patients also received a 50 mg dose. After the 20 mg dose the peak drug plasma concentration varied between 5 and 80 ng/ml (mean 33), and after the 50 mg dose between 14 and 212 ng/ml (mean 111). This variation is much greater than that seen in earlier studies on healthy volunteers and on a group of non-geriatric hypertensive patients. Plasma half-life of metoprolol averaged about 3.5 hours after both the 20 mg and the 50 mg dose; this does not differe from the plasma half-life in earlier studies in younger age groups. The variability observed in the study might be explained multifactorially, e.g. by different body weight, absorption and/or first-pass effect of the drug.
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PMID:Plasma levels and effect on heart rate and blood pressure of metoprolol after acute oral administration in 12 geriatric patients. 98 11

Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.
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PMID:Controlled release metoprolol formulations. A review of their pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and ischaemic heart disease. 137 20

Celiprolol is a 'third generation' beta-blocking agent which is claimed to avoid problems associated with simpler beta-blockers, such as vasoconstriction, bronchoconstriction and myocardial depression. A double-blind randomized study was undertaken in 30 patients with coronary artery disease and hypertension to compare the haemodynamic effects of single intravenous doses of 0.15 mg kg-1 celiprolol (N = 16) and metoprolol (N = 14). Following celiprolol administration, the tendency was for myocardial function to improve or remain unchanged; left ventricular end-systolic volume and ejection fraction improved significantly (P less than 0.05). However, following metoprolol administration, the tendency was for myocardial function to deteriorate, with significant falls in cardiac output (P less than 0.05), ejection fraction (P less than 0.05) and velocity of circumferential shortening (P less than 0.01). There was a tendency for peripheral resistance to fall slightly with celiprolol but to rise markedly with metoprolol (pNS). Left ventricular pressure-volume loops showed improved performance with celiprolol and deterioration with metoprolol. Both drugs resulted in increases in coronary flow and myocardial oxygen consumption (P less than 0.05). Metoprolol, but not celiprolol, resulted in some deterioration in regional left ventricular wall motion (P less than 0.05). Celiprolol appears to be haemodynamically advantageous compared to metoprolol in patients with coronary artery disease and hypertension.
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PMID:Acute haemodynamic profile of celiprolol in patients with coronary heart disease and hypertension: a double-blind comparison with metoprolol. 167 5

The aim of this review is to present an overview of the results of randomized primary preventive trials with beta-blockers in patients with hypertension. For statistical and biological reasons, any preventive effect on coronary events is hard to demonstrate in women in these primary preventive trials because of the low incidence of coronary events in middle-aged, white women. Therefore, special attention will be focused on the effect in men. Four beta-blockers have been studied: propranolol, oxprenolol, atenolol, and metoprolol. Results from the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial showed that the risk for coronary events was 24% lower in patients receiving beta-blockade compared with patients receiving diuretics (p less than 0.001). In men, three beta-blockers (propranolol, oxprenolol, and metoprolol) have shown significantly lower risk for coronary events (fatal and nonfatal) in the nonsmoking subgroup. Results from the MAPHY study also indicated a reduction in total and coronary mortality with the beta-blocker as compared with thiazide diuretics. The observed reduced risk for coronary events with beta-blockers as compared with diuretics is probably independent of the reduction in blood pressure. Mechanisms currently under study include antiatherosclerotic effects, antithrombotic effects, anti-ischemic effects, and antifibrillatory effects. It is not possible to judge, with present evidence, if all beta-blockers are equally effective in preventing sudden death and other coronary events.
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PMID:Beta-blockade in the primary prevention of coronary heart disease in hypertensive patients. Review of present evidence. 168 15


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