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At least 19 recordsLinked to original sources
PubMed1997

Addition of felodipine to metoprolol vs replacement of metoprolol by felodipine in patients with angina pectoris despite adequate beta-blockade. Results of the Felodipine ER and Metoprolol CR in Angina (FEMINA) Study. Working Group on Cardiovascular Research, The Netherlands (WCN).

AIMS: The study aimed to compare the addition of felodipine to metoprolol, and of the replacement of metoprolol by felodipine, with continuation of metoprolol, in patients with angina pectoris despite optimal beta-blockade. METHODS AND RESULTS: The study was double-blind, parallel, randomized and controlled, and comprised 363 patients from 27 outpatient cardiology clinics in the Netherlands. The patients had angina and positive bicycle exercise tests despite optimal beta-blockade (resting heart rate < 65 beats.min-1). Randomization was to three treatment groups: continuation of metoprolol (control), addition of felodipine to metoprolol, and replacement of metoprolol by felodipine. Exercise tests were repeated after 2 and 5 weeks. The main outcome measure was: exercise result after 5 weeks, compared with baseline, between-group comparison of changes vs control. There were no significant differences in exercise duration and onset of chest pain vs control. The addition of felodipine increased time until 1 mm ST depression (43 s, 95% confidence interval 20-65 s), and decreased both ST depression at highest comparable work load (0.46 mm, 95% confidence interval 0.19-0.72), and maximal ST depression (0.49 mm, 95% confidence interval 0.23-0.74). Exercise results after replacement of metoprolol by felodipine were not different from control, apart from a significant increase in rate pressure product. Significantly more patients experienced adverse events in the felodipine monotherapy group. CONCLUSION: Combination of metoprolol and felodipine is to be preferred to felodipine monotherapy in patients who have signs and symptoms of myocardial ischaemia despite optimal beta-blockade.

Adolescent↗
PubMed1990

The relationship between metoprolol plasma concentration and beta 1-blockade in healthy subjects: a study on conventional metoprolol and metoprolol CR/ZOK formulations.

Four studies using different daily doses (100 mg, 200 mg, 300 mg and 400 mg) have examined the bioequivalence of the once daily formulation metoprolol CR/ZOK and conventional metoprolol tablets (CT). These studies showed metoprolol CR/ZOK to have a similar beta 1-blocking activity to metoprolol CT but that the bioavailability of the new formulation was lower. This paper presents the analysis of data from all four studies, looking at the relationship between plasma concentrations and beta 1-blockade measured as reduction of exercise induced tachycardia. The log linear pharmacodynamic model was used for each of the four doses to compare the two formulations. Mean slopes and intercepts in the linear regression analysis of log plasma concentration of metoprolol versus beta 1-blockade did not differ significantly between CR/ZOK and CT in any of the four studies. After having shown lack of influence of the absorption rate of the plasma concentration-effect relationship, data for CR/ZOK and CT formulations from the 200 mg study were pooled for each individual subject and fitted to an Emax model. The maximal beta 1-blocking effect (Emax) was 28% (95% confidence interval: 25-31%) and the plasma concentration for obtaining 50% of Emax (C50) was 105 nmol/L (95% confidence interval: 74-135 nmol/L). The plasma concentration-effect data from the 100 mg, 300 mg and 400 mg studies were reasonably well within the 95% prediction interval based on the 200 mg study, which showed the validity of the obtained relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1982

Comparison of two long-acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing.

1 Eight healthy men received two long-acting formulations of metoprolol 200 mg (SA Astra, SR Geigy), conventional metoprolol 200 mg and atenolol 100 mg once daily for 1 week each in balanced, crossover fashion. There was a washout period of at least a week between each phase. 2 On the last day of each phase, post-exercise heart rate was recorded at intervals and compared to pretreatment values. Plasma metoprolol concentrations were measured. 3 The mean AUC was similar after each of the three formulations of metoprolol (relative bioavailability of SA and SR v conventional was 97%) but with SA and SR metoprolol the time to peak was significantly delayed by about 2 h. 4 In comparison to conventional metoprolol only metoprolol SA was associated with significantly higher plasma metoprolol concentrations at the end of a dosing interval (mean values: conventional, 25 ng/ml, SR 37 ng/ml, SA 51 ng/ml). 5 Mean (+/- s.d.) reduction in exercise tachycardia at the end of a dosing interval was significantly greater with atenolol (14.8 +/- 4.5%) and metoprolol SA (13.7 +/- 10.3%) than with metoprolol SR (10 +/- 8.4%) and conventional metoprolol (8.2 +/- 7.1%). 6 The variability in beta-adrenoceptor blockade at 24 h was much greater with each of the three metoprolol formulations than that with atenolol. This was explained by the variability in metoprolol metabolism. 7 Oxidation phenotype testing with debrisoquine showed there were six extensive metabolisers and two poor metabolisers. The AUC, half-life and response to metoprolol at 24 h were much greater in poor metabolisers. Response to atenolol was not influenced by phenotype.

Adult↗
PubMed1999

Similar risk reduction of death of extended-release metoprolol once daily and immediate-release metoprolol twice daily during 5 years after myocardial infarction.

The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metoprolol with regard to the risk reduction of death for 5 years postinfarction and to analyze whether treatment with the beta-blocker metoprolol is associated with a reduced mortality after the introduction of modern therapies such as thrombolysis, aspirin, and ACE inhibitors. All patients discharged after an acute myocardial infarction (AMI) from Sahlgrenska University Hospital (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Göteborg, Sweden, were included in the study. During Period I, 56% were prescribed immediate-release metoprolol compared with 61% prescribed extended-release metoprolol during Period II. Immediate-release metoprolol was not available for outpatient use during Period II. In a multivariate analysis, all variables significantly associated with either increased or decreased postinfarction mortality during Periods I and II (univariate analysis of patient characteristics, medical history, complications during the AMI medication at discharge) studied were with Cox's proportional hazards model. Treatment with immediate-release metoprolol was significantly associated with reduced mortality over 5 years during Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P < 0.0001; 95% CI for RR, 0.53-0.82). Thrombolysis and the use of aspirin and ACE inhibitors were more frequently used during Period II. The results showed that postinfarction treatment with extended-release metoprolol given once daily was associated with a similar risk reduction of death over 5 years as immediate-release metoprolol given twice daily. The data, furthermore, indicate that the beta-blocker metoprolol is associated with a reduced risk of death after the introduction of modern therapy such as thrombolysis, aspirin, and ACE inhibitors.

Adrenergic beta-Antagonists↗
PubMed1987

Disposition of the adrenergic blocker metoprolol and its metabolite OH-metoprolol in maternal plasma, amniotic fluid and capillary blood of the neonate.

Seven women were treated with metoprolol 50-100 mg twice daily for hypertension in pregnancy. The disposition of metoprolol and one of its metabolites alfa-OH-metoprolol was studied in venous plasma and amniotic fluid during labour, in mixed cord plasma and in capillary blood of the newborn. Peak concentrations of metoprolol and alfa-OH-metoprolol were reached 60 to 120 min after dosing in maternal plasma while the amniotic fluid levels of these compounds continued to increase from 60 to 180 min to the end of the study and were substantially higher than in the plasma after 4 to 5 h. It is postulated that a major fraction of metoprolol and alfa-OH-metoprolol reaches the amniotic fluid via the fetal urine and that the elimination from the amniotic fluid mainly proceeds via diffusion across fetal membranes and transfer across the fetal capillary bed. No measurable concentrations of metoprolol were found in two of the newborns 2 h after delivery. In the remaining four neonates the 2-h concentrations exceeded the corresponding cord plasma levels. In all neonates the alfa-OH-metoprolol levels in the capillary blood were higher 2 h after birth than in cord blood. In two newborns the metabolite levels continued to increase for 5 h and in one the highest blood concentrations of this metabolite was found 20 h after birth. Redistribution of metoprolol from tissue stores followed by metabolism might be the cause of these temporary elevations of the blood levels of metoprolol and alfa-OH-metoprolol.

Amniotic Fluid↗
PubMed1990

Pharmacokinetic and pharmacodynamic comparison of an osmotic release oral metoprolol tablet and the metoprolol conventional tablet.

Four double-blind, Latin-square studies were conducted to compare the pharmacokinetics and pharmacodynamic bioavailability of metoprolol OROS (oral osmotic) and the conventional tablet (CT) of metoprolol. Metoprolol OROS (7/95 mg or 14/190 mg) was administered once daily in doses equivalent to 100 mg of metoprolol CT given once, twice, thrice, and four times a day. In all four studies, lower peak plasma concentrations and longer times to peak were observed after metoprolol OROS than after metoprolol CT, indicating a controlled-release profile for metoprolol OROS. beta-Adrenergic blockade, as measured by reductions in exercise heart rate, was lower after metoprolol OROS than after metoprolol CT, but metoprolol OROS provided a smoother and more sustained beta-blockade. All four doses of metoprolol OROS at steady state produced relative pharmacodynamic bioavailability that ranged from 87% to 104% of that produced by equivalent doses of metoprolol CT.

Administration, Oral↗
PubMedDate not supplied

Lymphocyte beta 2-receptor activity, metoprolol kinetics, and response to metoprolol in hypertensive black men.

STUDY OBJECTIVES: To evaluate whether variability in S-metoprolol kinetics and lymphocyte beta 2-receptor-mediated cyclic adenosine monophosphate (cAMP) accumulation is related to the variability in antihypertensive response to metoprolol of black men. DESIGN: Prospective, unblinded study. SETTING: University-based preventive medicine clinic. PATIENTS: Twelve hypertensive black men. MEASUREMENTS AND MAIN RESULTS: Ambulatory blood pressure was measured over 24 hours before and after metoprolol administration. Ex vivo responsiveness of lymphocyte beta 2-receptors to isoproterenol was established for each subject before initiating metoprolol therapy. Plasma samples were collected over 12 hours at the conclusion of the study, from which metoprolol enantiomer concentrations were determined by chiral high-performance liquid chromatography, and kinetic values were calculated. The 24-hour ambulatory blood pressure responses to metoprolol were highly variable, with systolic blood pressure responses ranging from -13 to +33 mm Hg and diastolic blood pressure responses ranging from -15 to +15 mm Hg. There was a significant relationship between the metoprolol-induced change in systolic blood pressure and the maximum lymphocyte beta 2-receptor cAMP production (y = 0.47x-7.79; r2 = 0.49, p < 0.05) such that those with the highest maximum cAMP production had the greatest blood pressure increases during metoprolol therapy. There was no relationship between S-metoprolol concentration and blood pressure response. Mean oral clearance values for S- and R-metoprolol were 1320 and 2346 ml/minute, respectively. CONCLUSIONS: Lymphocyte beta 2-receptor data suggest that individuals most responsive to beta-receptor stimulation may be at greatest risk of blood pressure elevation during beta 2-receptor blockade. The metoprolol enantiomer kinetic data are markedly different from previously published data and may represent racial differences in pharmacokinetics.

Adult↗
PubMed1991

Effects of diltiazem and metoprolol on blood pressure, adverse symptoms and general well-being. The Swedish Diltiazem-Metoprolol Multi-Centre Study Group.

General well-being, adverse effects and anti-hypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were randomized to receive oral diltiazem 120-240-360 mg/day or metoprolol 50-100-200 mg/day. Each dose was given for a 4-week period as a forced titration regime. In all 119 patients, 59 and 60, respectively, on diltiazem and metoprolol completed the study protocol. There were dose-dependent reductions in supine and standing blood pressures (BP) after both diltiazem and metoprolol therapy. In the diltiazem group, supine BP was reduced by 10 (11)/10 (6) mmHg (SBP/DBP) at the highest dose level, and the corresponding values for the metoprolol group were 7 (16)/8 (9) mmHg (SBP/DBP). Target pressures (DBP less than or equal to 90 mmHg and/or a reduction in DBP of greater than or equal to 10%) were reached in 63% and 48% of the patients, respectively. The incidence and severity of dose-dependent adverse effects, as evaluated by spontaneous reports or open and direct questioning, did not differ between treatments. Subjective well-being, evaluated by a self-administered questionnaire, the MSE-profile, did not differ significantly between diltiazem and metoprolol therapy. However, after an initial slight deterioration, contentment and vitality tended to improve with increasing doses of diltiazem, while a dose-related deterioration in these variables was observed on metoprolol therapy. At the highest dose levels, contentment and vitality tended to be better in the diltiazem than the metoprolol group. Thus, diltiazem and metoprolol in daily doses of 120-360 mg and 50-200 mg, respectively, produce comparable and parallel reductions in supine and standing BP. However, while subjective well-being tended to improve with increasing doses of diltiazem, there was a negative trend for metoprolol. It is concluded that diltiazem, given as monotherapy to hypertensive patients, does not impair subjective well-being.

Adult↗
PubMed1988

Efficacy and tolerability of a new controlled-release formulation of metoprolol: a comparison with conventional metoprolol tablets in mild to moderate hypertension.

In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained greater than or equal to 95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure less than 95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.

Blood Pressure↗
PubMed1990

The effect of impaired renal function on the pharmacokinetics of metoprolol after single administration of a 14/190 metoprolol OROS system.

Renal function is known to sometimes have a significant effect on the pharmacokinetics of drugs or drug metabolites, which are eliminated in appreciable amounts by the kidneys. For this reason, we conducted a study to compare the plasma concentration profiles of metoprolol and its metabolite, alpha-hydroxymetoprolol (OH-metoprolol), in healthy volunteers and in renally impaired patients. Following a single oral dose of a 14/190 metoprolol OROS (oral osmotic) tablet, plasma metoprolol profiles were shown to be similar for both subject groups. However, in renally impaired patients, renal clearance of OH-metoprolol was reduced and mean plasma levels of OH-metoprolol were increased approximately two- to threefold in comparison with healthy volunteers. The accumulation of OH-metoprolol in plasma, however, is unlikely to contribute to the beta-blocking effect of metoprolol, since OH-metoprolol possesses only one tenth the activity of its parent compound.

Administration, Oral↗
PubMed1991

Diltiazem compared with metoprolol as add-on-therapies to diuretics in hypertension. Swedish Diltiazem-Metoprolol Multicentre Study Group.

In a randomized, double-blind, parallel group study, diltiazem was compared with metoprolol as add-on therapy to diuretic treatment in 115 patients with hypertension. Following a placebo and diuretic period of four weeks, patients were randomized to either slow release diltiazem 90 mg twice daily or metoprolol 100 mg once daily using a double dummy technique. If after four weeks a target supine diastolic blood pressure (DBP) less than or equal to 90 mmHg pressure was not reached, the doses of diltiazem and metoprolol were doubled. Supine inclusion systolic/diastolic blood pressures (SBP/DBP) at randomization were 158 +/- 13 (mean +/- SD)/102 +/- 5 mmHg in the diltiazem group and 158 +/- 17/101 +/- 6 mmHg in the metoprolol group. Active therapy significantly lowered SBP and DBP in both groups by 7-10%. Heart rate was significantly lowered in both groups, although the effect of metoprolol was more pronounced. Response rates (supine DBP less than or equal to 90 mmHg and/or decreased by greater than or equal to 10%) were 43% on diltiazem 90 mg twice daily and 52% on metoprolol 100 mg once daily, increasing to 82% and 62%, respectively, after dose escalations. No serious side effects were seen, but three patients, two on diltiazem and one on metoprolol, were withdrawn from the study due to severe headache, nausea and bradycardia respectively. of mild to moderate adverse reactions, tiredness was most frequent, occurring in 14.5% and 15.8% on active diltiazem and metoprolol therapy, respectively. We conclude that both diltiazem and metoprolol lower BP when added to diuretics in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

The antianginal efficacy and tolerability of controlled-release metoprolol once daily: a comparison with conventional metoprolol tablets twice daily.

In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were treated with 100 mg/day or 200 mg/day, depending on their previous beta-blocker dose. Antianginal efficacy was estimated by counting the number of anginal attacks, by noting the consumption of nitroglycerin tablets, and by exercise tolerance testing. Adverse effects were recorded by a standardized questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol CR preparation, given once daily, possesses the same antianginal efficacy as conventional metoprolol tablets, given twice daily, and may be better tolerated in patients susceptible to side-effects. The antianginal effect of metoprolol CR, 200 mg/day, may be greater over 24 h than that produced by conventional metoprolol tablets, 100 mg twice daily.

Adult↗
PubMed1993

Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group.

Several small studies have suggested beneficial effects of long-term beta-blocker treatment in idiopathic dilated cardiomyopathy. Our large multicentre study aimed to find out whether metoprolol improves overall survival and morbidity in this disorder. 383 subjects with heart failure from idiopathic dilated cardiomyopathy (ejection fraction < 0.40) were randomly assigned placebo or metoprolol. 94% were in New York Heart Association functional classes II and III, and 80% were receiving background treatment. A test dose of metoprolol (5 mg twice daily) was given for 2-7 days; those tolerating this dose (96%) entered randomisation. Study medication was increased slowly from 10 mg to 100-150 mg daily. There were 34% (95% CI -6 to 62%, p = 0.058) fewer primary endpoints in the metoprolol than the placebo group; 2 and 19 patients, respectively, deteriorated to the point of needing transplantation and 23 and 19 died. The change in ejection fraction from baseline to 12 months was significantly greater with metoprolol than with placebo (0.13 vs 0.06, p < 0.0001). Pulmonary capillary wedge pressure decreased more from baseline to 12 months with metoprolol than with placebo (5 vs 2 mm Hg, p = 0.06). Exercise time at 12 months was significantly greater (p = 0.046) in metoprolol-treated than in placebo-treated patients. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol prevented clinical deterioration, improved symptoms and cardiac function, and was well tolerated.

Adolescent↗
PubMed1990

Is metoprolol CR/ZOK more selective than conventional metoprolol and atenolol?

An alternative, simple method to assess beta 1-selectivity is to establish the impact of the beta blocker on beta 2-stimulated increases in plasma glucose and decreases in plasma potassium during an intravenous infusion of terbutaline. In the present study the effects of metoprolol CR/ZOK 100 mg, conventional metoprolol 100 mg, atenolol 100 mg, and placebo on these biochemical changes have been compared. In 12 healthy volunteers, terbutaline infusion of 6 micrograms/kg was administered intravenously over 1 hour. Three and a half hours before the infusion they were given a single dose of each of the four treatments in random order, single-blind. The maximum increase in plasma above baseline occurred at the end of a 60-minute terbutaline infusion. All three-beta blockers decreased the peak plasma glucose level achieved compared with placebo (P less than .01) but this reduction was significantly less with metoprolol CR/ZOK pretreatment than with atenolol (P less than .05). Similar results were seen for the AUC values for the curves obtained from the increments over the 60 minutes of the infusion and the subsequent 120 minutes after the infusion. In addition, both the AUC values and the maximum fall in potassium were significantly reduced by all treatments (P less than .05). The metoprolol CR/ZOK preparation produced significantly less effect than atenolol with respect to both AUC (P less than .05) and maximum fall (P less than .01) and significantly less effect than conventional metoprolol tablets in maximum fall (P less than .01). In conclusion, the metoprolol CR/ZOK formulation produces lower plasma concentrations and results in less effect on potassium and glucose compared to conventional metoprolol and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Pharmacokinetics of metoprolol and its metabolite alpha-OH-metoprolol in healthy, non-smoking, elderly individuals.

The absorption and disposition of metoprolol have been evaluated in 10 healthy, non-smoking, elderly individuals (mean age 73.1 years) by simultaneous determination of [3H]-metoprolol and unlabelled metoprolol. The labelled drug was given as an intravenous tracer dose, immediately followed by oral metoprolol 25 mg. The experiment was preceded by administration of metoprolol 25 mg b.i.d. for 3 days. The volume of distribution, elimination half-life and total body clearance were almost the same as previously observed in healthy, young subjects. The mean systemic availability was about 39% in the elderly, which is lower than the mean of 55% observed in a control group of young volunteers who received 50 mg b.i.d. In the elderly, the mean plasma concentration of alpha-OH-metoprolol was about twice as high as that of the parent drug, whereas the opposite was true of the control group. The results indicate that age-related physiological changes have a negligible effect on the pharmacokinetics of metoprolol.

Adult↗
PubMed1997

Effect of metoprolol on the prognosis for patients with suspected acute myocardial infarction and indirect signs of congestive heart failure (a subgroup analysis of the Göteborg Metoprolol Trial).

The aim of this study is to describe the impact of early treatment with metoprolol on prognosis during 1 year of follow-up in patients with suspected acute myocardial infarction (AMI) and indirect signs of congestive heart failure (CHF). Patients aged 40-74 years who presented within 48 hours of onset of symptoms raising suspicion of AMI were assessed for inclusion. All patients participated in the Göteborg Metoprolol Trial and had indirect indices of CHF according to various clinical criteria. As soon as possible after hospital admission, patients received either placebo or metoprolol (15 mg) divided into 3 intravenous injections, then oral treatment, 200 mg daily for 3 months. Thereafter, most patients in both treatment groups received metoprolol in an open manner. Among the 1,395 randomized patients, 262 (19%) had signs of mild-to-moderate CHF before randomization. Of these, 131 were randomized to metoprolol and 131 to placebo. During the first 3 months, mortality was 10% among patients randomized to metoprolol versus 19% among patients randomized to placebo (p = 0.036). The corresponding figures for the first year were 14% and 27%, respectively (p = 0.0099). Patients randomized to placebo who showed signs of CHF had a 1-year mortality rate of 28% compared with 10% among patients without such signs (p <0.001). The results suggest that early treatment with metoprolol markedly reduces mortality in patients having suspected AMI and signs of CHF.

Adrenergic beta-Antagonists↗
PubMed1993

A comparison of the beta 1-selectivity of conventional metoprolol and metoprolol CR during exercise in healthy volunteers.

This paper reports on a randomized double-blind crossover study to compare the effects of daily treatment with 100 mg conventional metoprolol (M100), 50 or 100 mg slow-release metoprolol CR (CR50, CR100) and placebo on the response to treadmill walking exercise in 12 healthy volunteers. Twenty minutes of exercise was undertaken at 1.5 h post-dose (Ex1) and again at 4 h (Ex2). During Ex1 all metoprolol preparations caused a reduction in the exercise-induced increase in heart rate when compared to placebo (P < 0.001). The exercise-induced increase in plasma glycerol, an indicator of lipolysis, was diminished by all metoprolol preparations but to a greater extent by M100 (P < 0.05). Rises in plasma ammonia were used to assess the net degradation of energy-rich adenine nucleotides by skeletal muscle during exercise. When compared to placebo, a significant elevation in plasma ammonia was seen only during exercise with M100 (P < 0.05). The perceived exertion at the end of exercise was also greatest on conventional metoprolol. The differences between the effects of conventional and CR formulations of metoprolol were less when exercise was repeated 4 h post dosing. We conclude that metoprolol CR may offer advantages over the conventional preparation, in subjects regularly engaging in exercise, by reducing the metabolic stress imposed upon skeletal muscle.

Adult↗
PubMed1989

Long-term beta-blockade in dilated cardiomyopathy. Effects of short- and long-term metoprolol treatment followed by withdrawal and readministration of metoprolol.

To evaluate the short- and long-term effects of beta-adrenergic blockade (metoprolol) as well as the reaction to withdrawal and readministration of metoprolol in severe heart failure, 33 patients (25 men and eight women; mean age, 47.6 +/- 14.0 years) with dilated cardiomyopathy were studied by right and left heart catheterization, right ventricular biopsy, two-dimensional and Doppler echocardiography, and external pulse recordings. Twenty-six of 33 patients survived more than 6 months, and 24 of the 26 patients improved their functional class (from mean 3.3 to 1.8, p less than 0.0001). These 24 patients were subjected to withdrawal of metoprolol until the number of symptoms increased and deterioration occurred as observed noninvasively (group 1, n = 16), whereas the eight patients did not deteriorate during a 12-month period (group 2). During long-term treatment with metoprolol, there was an increase in ejection fraction from 0.24 to 0.42 (p less than 0.0001), whereas there was a decrease in the left ventricular (LV) end-diastolic dimension (from 7.3 to 6.4 cm, p less than 0.0001), in the grade of mitral regurgitation (from 1.7 to 0.4, p less than 0.0001), and in the grade of tricuspid regurgitation (from 0.6 to 0.05, p less than 0.007). There was a decrease in pulmonary wedge pressure (from 23.8 to 10.7 mm Hg, p less than 0.0001), LV end-diastolic pressure (from 24.1 to 13.4 mm Hg, p less than 0.002), and systolic vascular resistance (from 1,782 to 1,499 dynes/sec/cm, p less than 0.04). There was an increase in systolic blood pressure (from 116 to 132 mm Hg, p less than 0.003), cardiac index (from 2.17 to 2.58 l/min/m2, p less than 0.005), and LV stroke work index (from 31 to 65 g.m/m2, p less than 0.0001). During withdrawal of metoprolol, the heart rate and left atrial dimension increased (p less than 0.0001), whereas ejection fraction decreased (p less than 0.0001). The 12 (of 16) patients in group 1 who survived the withdrawal period had metoprolol readministered, and subsequently, ejection fraction increased (from 0.23 to 0.33, p less than 0.002). Patients had a low number of ventricular beta-adrenergic receptors compared with healthy control subjects (30.3 +/- 2.9 vs. 97.4 +/- 8.7 fmol/mg protein, p less than 0.001), but long-term treatment with metoprolol caused a moderate up-regulation (from 30.3 +/- 2.9 to 49.0 +/- 7.1 fmol/mg protein, p less than 0.05), which may facilitate a more normal response to sympathetic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗