-
Pharmacological Research Aug 2019Sympathetic activity plays an important role in modulation of cardiac rhythm. Indeed, while exerting positive tropic effects in response to physiologic and pathologic... (Review)
Review
Sympathetic activity plays an important role in modulation of cardiac rhythm. Indeed, while exerting positive tropic effects in response to physiologic and pathologic stressors, β-adrenergic stimulation influences cardiac electrophysiology and can lead to disturbances of the heart rhythm and potentially lethal arrhythmias, particularly in pathological settings. For this reason, β-blockers are widely utilized clinically as antiarrhythmics. In this review, the molecular mechanisms of β-adrenergic action in the heart, the cellular and tissue level cardiac responses to β-adrenergic stimulation, and the clinical use of β-blockers as antiarrhythmic agents are reviewed. We emphasize the complex interaction between cardiomyocyte signaling, contraction, and electrophysiology occurring over multiple time- and spatial-scales during pathophysiological responses to β-adrenergic stimulation. An integrated understanding of this complex system is essential for optimizing therapies aimed at preventing arrhythmias.
Topics: Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Humans; Myocardium
PubMed: 31100336
DOI: 10.1016/j.phrs.2019.104274 -
European Journal of Internal Medicine Jun 2021β-blockers represent a mainstay in the pharmacological approach to patients affected by heart failure with reduced ejection fraction (HFrEF). However, underuse of this... (Review)
Review
β-blockers represent a mainstay in the pharmacological approach to patients affected by heart failure with reduced ejection fraction (HFrEF). However, underuse of this class of drugs is still reported, especially in the presence of cardiovascular and non-cardiovascular comorbidities, even if they are not contraindications for prescription of a β-blocker. The prognostic benefit of β-blockers is relevant in the presence of comorbidities, and achievement of the maximum tolerated dose is an important goal to increase their favorable prognostic role. The aim of the present review is to analyze the available evidence on the use of β-blockers in HFrEF patients with the most common comorbidities. In particular, we will discuss the role and most appropriate beta-blocker in patients with pulmonary disease (bisoprolol, metoprolol, nebivolol), diabetes (carvedilol and nebivolol), atrial fibrillation (all indicated for rate control, with metoprolol as the first choice followed by bisoprolol, nebivolol, and carvedilol), erectile dysfunction (bisoprolol and nebivolol), peripheral arterial disease (nebivolol), and other conditions, in order to clarify the correct use of this class of drugs in the clinical practice.
Topics: Adrenergic beta-Antagonists; Carbazoles; Heart Failure; Humans; Male; Propanolamines; Stroke Volume
PubMed: 33941435
DOI: 10.1016/j.ejim.2021.03.035 -
Pharmacological Research Jan 2020The pharmacological class of β-blockers includes a plea of molecules with largely different pharmacokinetic and pharmacodynamic characteristics with a protective effect... (Review)
Review
The pharmacological class of β-blockers includes a plea of molecules with largely different pharmacokinetic and pharmacodynamic characteristics with a protective effect that may span far beyond the cardiovascular system. Although all these compounds share the pharmacological blockade of the adrenergic receptors, each of them is characterized by specific pharmacological properties, including selectivity of action depending on the adrenergic receptors subtypes, intrinsic sympathomimetic activity (ISA), lipid solubility, pharmacokinetic profile, and also other ancillary properties that impact their clinical effect. Their use in the treatment of hypertension has been extensively debated and at the moment a class indication is not present. However, in specific niche of patients, such as in those young individuals in which hypertension is mainly driven by a sympathetic hyperactivation, strong evidence pose β-Blockers as a highly reasonable first-line treatment. Lipophilic β-blockers, specifically propranolol and metoprolol, can cross the Blood Brain Barrier and have a Class A indication for the prophylactic treatment of migraine attacks. Moreover, since β-adrenergic receptors affect the proliferative process of both cancer and immune cells, their blockade has been associated with metastasis reduction in several epithelial and solid organ tumors posing β-Blockers as a new attractive, inexpensive and relatively safe therapeutic strategy in patients with several types of cancer. However, further dedicated prospective, randomized, placebo-controlled studies are needed to determine the real efficacy of these compounds.
Topics: Adrenergic beta-Antagonists; Animals; Humans; Hypertension; Migraine Disorders; Neoplasms
PubMed: 31809852
DOI: 10.1016/j.phrs.2019.104587 -
Annales Pharmaceutiques Francaises Sep 2022Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical... (Review)
Review
OBJECTIVES
Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical structure, pharmacokinetic and pharmacodynamic properties (absorption, bioavailability, metabolism, hydrophilic or lipophilic character, selective or non-selective nature, the presence or absence of intrinsic sympathomimetic activity), which may confer different antiarrhythmic properties to different beta-blockers. The aim of this study was to analyze the current existing evidence for bisoprolol for the treatment of both supraventricular and ventricular arrhythmias.
MATERIAL AND METHODS
Using the keywords "bisoprolol" and "arrhythmias" or "atrial fibrillation" or "ventricular tachycardia" or "premature ventricular complexes" or "ventricular fibrillation", the Medline database was searched for articles in English or French until April 2020 assessing the role of bisoprolol in the treatment of arrhythmias. Data was then analyzed according to the type of arrhythmia treated and the quality of evidence using the GRADE approach.
RESULTS
A total of 325 studies were identified, of which 28 were considered relevant to the current topic. Among these studies, 19 assessed the role of bisoprolol for the treatment of supraventricular arrhythmias, 8 its role in treating ventricular arrhythmias and 1 its role in supraventricular and ventricular arrhythmias. The quality of evidence varied from low (7 studies) to high (5 studies).
CONCLUSION
Current evidence exists supporting the use of bisoprolol for the treatment of supraventricular arrhythmias, especially for rate control during atrial fibrillation. Evidence also exists for its efficacy in the treatment of ventricular arrhythmias, both in primary and in secondary prevention.
Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Bisoprolol; Humans
PubMed: 35093388
DOI: 10.1016/j.pharma.2022.01.007 -
Basic & Clinical Pharmacology &... Aug 2019Beta-blocker overdose is potentially harmful due to the strong blood pressure-lowering and heart rate-lowering effects. However, conflicting data exist as to their...
Beta-blocker overdose is potentially harmful due to the strong blood pressure-lowering and heart rate-lowering effects. However, conflicting data exist as to their differential toxicity, single-substance exposures and the effect of co-exposure with additional antihypertensive medication. For this, a 10-year retrospective, explorative analysis of the Mainz Poison Center/Germany database with regard to circumstances of beta-blocker exposure, doses, symptoms and treatment was carried out. Analyses were restricted to adult patients with single-substance exposures and co-exposures with one additional antihypertensive substance. Written follow-up information was obtained in half the cases. A total of 2967 cases were analysed, of which 697 were single-substance exposures. Metoprolol was most frequently reported followed by bisoprolol, atenolol, propranolol and sotalol. Metoprolol showed a linear dose-symptom relationship, whereas propranolol and sotalol seemed to have a threshold dose beyond which symptoms aggravated. Symptoms did not differ substantially, except for more seizures being reported with propranolol, and more CNS depression/vomiting with sotalol. Activated charcoal was used in 38%, gastric lavage in 11%, temporary pacemaker in 3%, glucagon in 1%, intubation for respiratory insufficiency and cardiopulmonary resuscitation in 1% and 0.5%. All patients recovered. In 174 co-exposure cases, the distribution of poisoning severity and rate of worsening of symptoms was comparable with single-substance exposures except one patient deceased after bisoprolol and verapamil co-exposure. In adults with beta-blocker overdose, no significant differences in poisoning severity among beta-blockers were detected, and no fatalities were observed with single-substance exposures. Co-exposures with other antihypertensives, sedatives or alcohol should be carefully attended to as fatalities might occur.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Charcoal; Dose-Response Relationship, Drug; Drug Overdose; Female; Gastric Lavage; Germany; Humans; Male; Middle Aged; Poison Control Centers; Retrospective Studies; Severity of Illness Index; Treatment Outcome
PubMed: 30916882
DOI: 10.1111/bcpt.13231 -
JACC. Heart Failure Aug 2015This study sought to evaluate the effects of beta-blocker withdrawal in acute decompensated heart failure (ADHF). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study sought to evaluate the effects of beta-blocker withdrawal in acute decompensated heart failure (ADHF).
BACKGROUND
Published reports showed trends for either no harm or increased risk of in-hospital mortality, short-term mortality, and rehospitalization rates in patients admitted for ADHF that discontinued beta-blockers; however, a comprehensive analysis has not been conducted.
METHODS
Relevant studies from January 2000 through January 2015 were identified in the PubMed, EMBASE, and COCHRANE electronic databases. Where appropriate data were available, weighted relative risks were estimated using random-effects meta-analysis techniques.
RESULTS
Five observational studies and 1 randomized clinical trial (n = 2,704 patients who continued beta-blocker therapy and n = 439 patients who discontinued beta-blocker therapy) that reported the short-term effects of beta-blocker withdrawal in ADHF were included in the analyses. In 2 studies, beta-blocker withdrawal significantly increased risk of in-hospital mortality (risk ratio: 3.72; 95% confidence interval [CI]: 1.51 to 9.14). Short-term mortality (relative risk: 1.61; 95% CI: 1.04 to 2.49; 4 studies) and combined short-term rehospitalization or death (relative risk: 1.59; 95% CI: 1.03 to 2.45; 4 studies) were also significantly increased.
CONCLUSIONS
Discontinuation of beta-blockers in patients admitted with ADHF was associated with significantly increased in-hospital mortality, short-term mortality, and the combined endpoint of short-term rehospitalization or mortality. These data suggest beta-blockers should be continued in ADHF patients if their clinical picture allows.
Topics: Adrenergic beta-Antagonists; Heart Failure; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Survival Rate
PubMed: 26251094
DOI: 10.1016/j.jchf.2015.03.008 -
Circulation Research Nov 2018The actions and regulation of cardiomyocyte βARs differ in several respects from the properties described for the prototypical βAR subtype; a mechanism to explain the... (Review)
Review
The actions and regulation of cardiomyocyte βARs differ in several respects from the properties described for the prototypical βAR subtype; a mechanism to explain the unique properties of the βAR subtype has never been obvious. This viewpoint summarizes recent studies that identify a novel signaling paradigm for the βAR, implicating the N-terminus as a molecular determinant of βAR responsiveness.
Topics: Adrenergic beta-Antagonists; Animals; Heart Diseases; Humans; Myocytes, Cardiac; Receptors, Adrenergic, beta
PubMed: 30571467
DOI: 10.1161/CIRCRESAHA.118.313884 -
Ugeskrift For Laeger Mar 2019
Topics: Adrenergic beta-Antagonists; Anxiety Disorders; Humans; Propranolol
PubMed: 30931879
DOI: No ID Found -
Journal of the American College of... Apr 2022
Topics: Adrenergic beta-Antagonists; Cardiomyopathy, Hypertrophic; Exercise Test; Hemodynamics; Humans
PubMed: 35450574
DOI: 10.1016/j.jacc.2022.02.021 -
JAMA Pediatrics Jan 2022Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic β-blockers, such as nadolol, may be... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic β-blockers, such as nadolol, may be preferable in individuals who experience propranolol unresponsiveness or adverse events.
OBJECTIVE
To document the noninferiority and safety of oral nadolol compared with oral propranolol in infants with IH.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind noninferiority prospective study with a noninferiority margin of 10% compared propranolol with nadolol in infants aged 1 to 6 months with problematic IH. The study was conducted in 2 academic pediatric dermatology centers in Canada between 2016 and 2020. Infants aged 1 to 6 months with a hemangioma greater than 1.5 cm on the face or 3 cm or greater on another body part causing or with potential to cause functional impairment or cosmetic disfigurement.
INTERVENTIONS
Oral propranolol and nadolol in escalating doses up to 2 mg/kg/d.
MAIN OUTCOMES AND MEASURE
Between-group differences comparing changes in the bulk (size and extent) and color of the IH at week 24 with baseline using a 100-mm visual analog scale.
RESULTS
The study included 71 patients. Of these, 36 were treated with propranolol. The mean (SD) age in this group was 3.1 (1.4) months, and 31 individuals (86%) were female. Thirty-five infants were treated with nadolol. The mean (SD) age in this group was 3.2 (1.6) months, and 26 individuals (74%) were female. The difference in IH between groups by t test was 8.8 (95% CI, 2.7-14.9) for size and 17.1 (95% CI, 7.2-30.0) for color in favor of the nadolol group, demonstrating that nadolol was noninferior to propranolol. Similar differences were noted at 52 weeks: 6.0 (95% CI, 1.9-10.1) and 10.1 (95% CI, 2.9-17.4) for size and color improvement, respectively. For each doubling of time unit (week), the coefficient of involution was 2.4 (95% CI, 0.5-4.4) higher with nadolol compared with propranolol. Safety data were similar between the 2 interventions.
CONCLUSIONS AND RELEVANCE
Oral nadolol was noninferior to oral propranolol, indicating it may be an efficacious and safe alternative in cases of propranolol unresponsiveness or adverse events, or when faster involution is required.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02505971.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Double-Blind Method; Equivalence Trials as Topic; Female; Hemangioma, Capillary; Humans; Infant; Male; Nadolol; Neoplastic Syndromes, Hereditary; Ontario; Propranolol; Prospective Studies; Treatment Outcome
PubMed: 34747977
DOI: 10.1001/jamapediatrics.2021.4565