Cardiovascular Effects of Beta-Blockers with and without Intrinsic Sympathomimetic Activity

SummaryIn an experimental study in 50 dogs the myocardial uptake of free fatty acids (FFAs) after beta-blockade was determined using radioiodinated heptadecanoic acid as a metabolic tracer. All 4 beta-blockers used (metoprolol, timolol, propranolol and pindolol) lowered the uptake of FFAs in the normal canine heart. Uptake of FFAs was also diminished after coronary artery occlusion per se, but administration of beta-blockers exerted little additional influence on the uptake of FFAs. This observation was qualitatively parallelled by the uptake of 201T1 in concomitant experiments. Plasma FFA levels were increased by pindolol (non-selective with intrinsic sympathomimetic activity), not changed by metoprolol (a cardioselective betablocking agent) and lowered by timolol and propranolol (both nonselective compounds). The extent of ischemic tissue, as reflected by uptake of iodoheptadecanoic acid and 201T1, was diminished by metoprolol but not by other beta-blockers. Regional distribution of both tracers, as shown in the endo-epicardial uptake ratios, was hardly influenced by beta-blockade, except for a small increase of 201T1 uptake in non-occluded endocardium. Uptake of 201T1 as well as of iodoheptadecanoic acid in the ischemic area was increased by metoprolol, timolol and propranolol and decreased by pindolol. We conclude that beta-blocking agents confer different effects on myocardial uptake and metabolism of FFAs which might possibly be related to their different inherent properties.

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Bisoprolol: Is This Just Another Beta-Blocker for Hypertension or Angina?

Annals of Pharmacotherapy ◽

10.1177/106002809502900412 ◽

1995 ◽

Vol 29 (4) ◽

pp. 403-414 ◽

Cited By ~ 8

Author(s):

Thomas E Johns ◽

Larry M Lopez

Keyword(s):

Beta Blockers ◽

Data Extraction ◽

Renal Plasma Flow ◽

Experimental Studies ◽

Plasma Lipid ◽

Plasma Renin ◽

Intrinsic Sympathomimetic Activity ◽

Study Selection ◽

Blood Pressures ◽

Dose Combination

Objective: To review the pharmacology, pharmacokinetics, and clinical experience with bisoprolol and make recommendations regarding its potential clinical usefulness, as well as considerations for formulary inclusion. To review the clinical pharmacology of torsemide and to compare it with currently available loop diuretics, particularly furosemide. Data Sources: Reference citations were sought from Index Medicus and Science Citation Index. Data were collected from abstracts and articles describing experimental studies or blind clinical trials. Study Selection: Studies designed in a randomized, blind, and placebo-controlled manner were emphasized. Studies also were included if bisoprolol was evaluated comparatively with other agents in a randomized, blind fashion. Data Extraction: Data from human studies published in English were evaluated. Studies were assessed by sample size and the clarity of descriptions of methods and results. Data Synthesis: Bisoprolol reduces systolic and diastolic blood pressures in patients with hypertension for a 24-hour dosing interval and is associated with beneficial hemodynamic effects in patients with myocardial ischemia. It is devoid of intrinsic sympathomimetic activity and membrane-stabilizing effects at therapeutic dosages. In patients with hypertension, bisoprolol diminishes plasma renin activity, platelet aggregation, effective renal plasma flow, and creatinine clearance. Bisoprolol has minimal effects on glucose tolerance and plasma lipid profiles. Monotherapy with bisoprolol is as effective as with atenolol, nitrendipine, or nifedipine. Low-dose combination therapy with hydrochlorothiazide is at least as effective as either bisoprolol or hydrochlorothiazide alone. Preliminary experience in the management of angina pectoris suggests that bisoprolol is at least as efficacious as atenolol or verapamil. Thus far, reported adverse effects are similar to those of other beta-blockers. No clinically important drug interactions have been reported at this time. Conclusions: Bisoprolol, alone or in combination with hydrochlorothiazide, is safe and effective for the short-term management of hypertension. Its efficacy in the management of stable angina requires further investigation. There is little clinical evidence that distinguishes bisoprolol from other beta-blockers; therefore, its inclusion on an institutional formulary is not recommended.

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Effectiveness and safety of concurrent beta-blockers and inhaled bronchodilators in COPD with cardiovascular comorbidities

European Respiratory Review ◽

10.1183/16000617.0123-2016 ◽

2017 ◽

Vol 26 (145) ◽

pp. 160123 ◽

Cited By ~ 8

Author(s):

Salvatore Corrao ◽

Giuseppe Brunori ◽

Umberto Lupo ◽

Francesco Perticone

Keyword(s):

Cardiovascular Diseases ◽

Respiratory Symptoms ◽

Beta Blockers ◽

Cardiovascular Effects ◽

Chronic Respiratory Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Cardiovascular Comorbidities ◽

Concurrent Use ◽

Copd Patients

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease and its prevalence is increasing worldwide, in both industrialised and developing countries. Its prevalence is ∼5% in the general population and it is the fourth leading cause of death worldwide. COPD is strongly associated with cardiovascular diseases; in fact, ∼64% of people suffering from COPD are treated for a concomitant cardiovascular disease and approximately one in three COPD patients die as a consequence of cardiovascular diseases.Inhaled bronchodilators might have adverse cardiovascular effects, including ischaemic events and arrhythmias, and beta-blockers might adversely influence the respiratory symptoms and the response to bronchodilators. For these reasons, it is important to know the safety profiles and the possible interactions between these two classes of drug, in order to prescribe them with greater awareness.In this article, we review the literature about the epidemiology of COPD, its association with cardiovascular diseases, and the safety of concurrent use of inhaled bronchodilators and beta-blockers, as a tool for improving the approach to complex therapies in clinical practice.

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Obesity and Beta-Blockers: Influence of Body Fat on Their Kinetics and Cardiovascular Effects

The Journal of Clinical Pharmacology ◽

10.1002/j.1552-4604.1989.tb03315.x ◽

1989 ◽

Vol 29 (3) ◽

pp. 212-216 ◽

Cited By ~ 16

Author(s):

Ferruccio Galletti ◽

Maria Luisa Fasano ◽

Liberato Aldo Ferrara ◽

Angelo Groppi ◽

Maria Montagna ◽

...

Keyword(s):

Body Fat ◽

Beta Blockers ◽

Cardiovascular Effects

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Pharmacokinetic/pharmacodynamic modeling of the cardiovascular effects of beta blockers in humans

Archives of Pharmacal Research ◽

10.1007/s12272-001-1231-4 ◽

2008 ◽

Vol 31 (6) ◽

pp. 814-821 ◽

Cited By ~ 12

Author(s):

In-hwan Baek ◽

Min-hyuk Yun ◽

Hwi-yeol Yun ◽

Kwang-il Kwon

Keyword(s):

Beta Blockers ◽

Cardiovascular Effects ◽

Pharmacodynamic Modeling

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Comparison Oftheocular Beta-Blockers

Annals of Pharmacotherapy ◽

10.1177/106002809603000109 ◽

1996 ◽

Vol 30 (1) ◽

pp. 43-54 ◽

Cited By ~ 54

Author(s):

Suellyn J Sorensen ◽

Steven R Abel

Keyword(s):

Intraocular Pressure ◽

Adverse Effects ◽

Therapeutic Response ◽

Open Angle Glaucoma ◽

Beta Blockers ◽

The Other ◽

Optic Disk ◽

Intrinsic Sympathomimetic Activity ◽

Timolol Maleate ◽

Local Tolerability

OBJECTIVE: To compare the similarities and differences among the ocular beta-blockers. Important considerations when comparing these agents are the differences in systemic adverse effects, local tolerability, and cost. DATA SOURCE: Information was retrieved from a MEDLINE search of the English-language literature and bibliographic reviews of review articles. Index terms included beta-blockers, glaucoma, timolol, levobunolol, betaxolol, metipranolol, and Carteolol. STUDY SELECTION: Emphasis was placed on eyedrop studies, as well as properly designed and executed clinical trials that assessed dosage, dosing interval, therapeutic response, adverse effects, and cost. DATA EXTRACTION: Data from several studies were evaluated according to the study design, therapeutic response, and adverse effects. DATA SYNTHESIS: Timolol maleate, levobunolol, metipranolol, and Carteolol have similar effectiveness in lowering intraocular pressure; however, levobunolol and timolol gel forming solution may have an advantage of once-daily dosing. Studies have not been published comparing the clinical efficacy of timolol hemihydrate with that of other ocular beta-blockers. Metipranolol is cost effective in treating primary open-angle glaucoma; however, it has been associated with more ocular burning, stinging, and granulomatous anterior uveitis than other agents. The intrinsic sympathomimetic activity of Carteolol has not yet displayed a definite advantage over the other agents in terms of optic disk perfusion and systemic adverse effects. The control of intraocular pressure with betaxolol has not always been as good as with timolol; however, betaxolol has some advantages over timolol and the other topical beta-blockers in terms of systemic adverse effects. CONCLUSIONS: Considering cost, efficacy, and safety, timolol maleate is the recommended formulary agent because the other agents cannot consistently show an outstanding advantage.

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Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.257.2.r259 ◽

1989 ◽

Vol 257 (2) ◽

pp. R259-R264

Author(s):

P. Bouissou ◽

F. X. Galen ◽

J. P. Richalet ◽

M. Lartigue ◽

F. Devaux ◽

...

Keyword(s):

Heart Rate ◽

Beta Blockers ◽

Placebo Treatment ◽

Beta Blockade ◽

Intrinsic Sympathomimetic Activity ◽

Exercise Tests ◽

Beta Adrenoceptor ◽

Significant Difference ◽

Exercise Induced ◽

Response To Exercise

In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

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