-
Drugs Jun 2023Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF) and... (Review)
Review
Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF) and consists of the four main drug classes: renin-angiotensin system inhibitors, evidence-based β-blockers, mineralocorticoid inhibitors and sodium glucose cotransporter 2 inhibitors. The recommendation for use of GDMT is based on the results of multiple major randomized controlled trials demonstrating improved clinical outcomes in patients with HFrEF who are maintained on this therapy. The effect is most beneficial when medications from the four main drug classes are used in conjunction. Despite this, there is an underutilization of GDMT, partially due to lack of awareness of how to safely and effectively initiate and titrate these medications. In this review article, we describe the different drug classes included in GDMT and offer an approach to initiation and effective titration in both the inpatient as well as outpatient setting.
Topics: Humans; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume
PubMed: 37254024
DOI: 10.1007/s40265-023-01887-4 -
Mini Reviews in Medicinal Chemistry 2016It has been over half a century since propranolol, the first beta-blocker, was developed for medical treatment. Since that time a large number of compounds from this... (Review)
Review
It has been over half a century since propranolol, the first beta-blocker, was developed for medical treatment. Since that time a large number of compounds from this group have been synthesised and many are now in clinical use. The structure, function, pharmacokinetics, and mechanism of beta-blockers have been established. The possibilities for their use in treating different conditions continue to evolve. Since the discovery of later generation beta-blockers, such as carvedilol and nebivolol, the search for new compounds continues, and may include known substances with beta-blocking properties which could extend their therapeutic potential.
Topics: Adrenergic beta-Antagonists; Chemistry, Pharmaceutical; Glaucoma; Humans; Hypertension; Hyperthyroidism; Migraine Disorders; Molecular Structure
PubMed: 26471965
DOI: 10.2174/1389557515666151016125948 -
Current Hypertension Reviews 2019Beta-adrenergic receptors are expressed in cardiomyocytes and activated by either noradrenaline released from sympathetic synapses or circulating catecholamines. Their... (Review)
Review
BACKGROUND
Beta-adrenergic receptors are expressed in cardiomyocytes and activated by either noradrenaline released from sympathetic synapses or circulating catecholamines. Their corresponding receptors have three subtypes, namely, β1, β2 and β3, which are members of the G protein-coupled receptors (GPCRs) family. Activation of β1-adrenergic receptors causes various physiological reactions including cardiac contraction and renin secretion from juxtaglomerular cells of the kidney. Antagonists of β-adrenergic receptors, known as β-blockers, have been used effectively for over four decades and have beneficial effects in the treatment of cardiovascular diseases. There are three generations of β-blockers according to their pharmacological properties. Firstgeneration β-blockers are non-selective, blocking both β1- and β2-receptors; second-generation β- blockers are more cardioselective in that they are more selective for β1-receptors; and thirdgeneration β-blockers are highly selective drugs for β1-receptors. The latter also display vasodilator actions by blocking α1-adrenoreceptors and activating β3-adrenergic receptors. In addition, thirdgeneration β-blockers exhibit angiogenic, antioxidant, anti-proliferative, anti-hypertrophic and antiapoptotic activities among other effects that are still under investigation.
CONCLUSION
The objective of this review is to describe the evolution observed during the development of the three distinctive generations, thereby highlighting the advantages of third-generation β- blockers over the other two drug classes.
Topics: Adrenergic beta-Antagonists; Animals; Cardiovascular Agents; Heart Diseases; Humans; Myocytes, Cardiac; Receptors, Adrenergic, beta; Signal Transduction; Treatment Outcome
PubMed: 30227820
DOI: 10.2174/1573402114666180918102735 -
Profiles of Drug Substances,... 2017Propranolol is a noncardioselective β-blocker. It is reported to have membrane-stabilizing properties, but it does not own intrinsic sympathomimetic activity....
Propranolol is a noncardioselective β-blocker. It is reported to have membrane-stabilizing properties, but it does not own intrinsic sympathomimetic activity. Propranolol hydrochloride is used to control hypertension, pheochromocytoma, myocardial infarction, cardiac arrhythmias, angina pectoris, and hypertrophic cardiomyopathy. It is also used to control symptoms of sympathetic overactivity in the management of hyperthyroidism, anxiety disorders, and tremor. Other indications cover the prophylaxis of migraine and of upper gastrointestinal bleeding in patients with portal hypertension. This study provides a detailed, comprehensive profile of propranolol, including formulas, elemental analysis, and the appearance of the drug. In addition, the synthesis of the drug is described. The chapter covers the physicochemical properties, including X-ray powder diffraction, pK, solubility, melting point, and procedures of analysis (spectroscopic, electrochemical, and chromatographic). In-depth pharmacology is also presented (pharmacological actions, therapeutic dosing, uses, Interactions, and adverse effects and precautions). More than 60 references are given as a proof of the abovementioned studies.
Topics: Adrenergic beta-Antagonists; Drug Stability; Humans; Hypertension; Molecular Structure; Propranolol
PubMed: 28431779
DOI: 10.1016/bs.podrm.2017.02.006 -
The American Journal of Medicine Jul 2019Beta-blockers are commonly used medications, and they have been traditionally considered "cardioprotective." Their clinical use appears to be more widespread than the... (Review)
Review
Beta-blockers are commonly used medications, and they have been traditionally considered "cardioprotective." Their clinical use appears to be more widespread than the available evidence base supporting their role in cardioprotection. Beta-blockers counteract neurohumoral activation in heart failure with reduced ejection fraction and offer both symptomatic improvement and reduction in adverse events. On the other hand, the use of beta-blockers in uncomplicated hypertension results in suboptimal outcomes compared to the established first-line antihypertensive agents. Providers at all levels should be familiar with common misconceptions regarding beta-blocker use in routine clinical practice.
Topics: Adrenergic beta-Antagonists; Cardiotonic Agents; Coronary Artery Disease; Heart Failure; Humans; Hypertension
PubMed: 30817899
DOI: 10.1016/j.amjmed.2019.01.039 -
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 -
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 -
Current Problems in Cardiology May 2023Heart failure with reduced ejection fraction (HFrEF) is a complex and progressive clinical condition characterized by dyspnea and functional impairment. HFrEF has a high... (Review)
Review
Heart failure with reduced ejection fraction (HFrEF) is a complex and progressive clinical condition characterized by dyspnea and functional impairment. HFrEF has a high burden of mortality and readmission rate making it one of the most significant public health challenges. Basic treatment strategies include diuretics for symptom relief and use of quadruple therapy (Angiotensin receptor blocker/neprilysin inhibitors, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors) for reduction in hospitalizations, all-cause mortality, and cardiovascular mortality. Despite compelling evidence of clinical benefit, guideline directed medical therapy is vastly underutilized in the real-world clinical practice. Other medications such as intravenous iron, ivabradine, hydralazine/nitrates and vericiguat may also have a role in certain subgroup of HFrEF patients. Specific groups of patients with HFrEF may also be candidates for various device therapies such as implanted cardioverter defibrillators, cardiac resynchronization therapy and trans catheter mitral valve repair. This review provides a comprehensive overview of drug and device management approaches for patients with HFrEF, recommendations for initiation and titrations of therapies, and challenges associated with guideline directed medical therapy in the management of patients with HFrEF (Graphical abstract).
Topics: Humans; Heart Failure; Angiotensin-Converting Enzyme Inhibitors; Stroke Volume; Adrenergic beta-Antagonists; Diuretics
PubMed: 36681212
DOI: 10.1016/j.cpcardiol.2023.101596 -
The Canadian Journal of Cardiology Apr 2019β-Blockers are a cornerstone of therapy for cardiovascular disease, but their clinical benefits are not consistent across the class and specific agents are preferred...
β-Blockers are a cornerstone of therapy for cardiovascular disease, but their clinical benefits are not consistent across the class and specific agents are preferred for certain indications. Further, when prescribed, a patient's clinical status might change, requiring the cardiologist to switch to an alternate agent. Examples of such scenarios include the development or a worsening of chronic noncardiac diseases (eg, hyperthyroidism, renal failure), new cardiac-related disease (eg, heart failure, atrial fibrillation), or practical/safety issues (eg, pregnancy, cost, side effects). However, guidelines on how to best switch to a different β-blocker are lacking. Additionally, most hospital-based formularies and guidelines do not provide recommendations around common challenges, like medication intolerance or adjustments for acute illness. We present a practical approach to switching between commonly prescribed β-blockers, which considers drug interchangeability for various indications, rationale for switching, necessary initial adjustments to dose/frequency, and differences in target/maximal doses.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Substitution; Humans
PubMed: 30935645
DOI: 10.1016/j.cjca.2019.01.013 -
Hypertension (Dallas, Tex. : 1979) Jun 2022Several hypertension guidelines have removed beta-blockers from their previous position as first-choice drugs for the treatment of hypertension. However, this... (Review)
Review
Individualized Beta-Blocker Treatment for High Blood Pressure Dictated by Medical Comorbidities: Indications Beyond the 2018 European Society of Cardiology/European Society of Hypertension Guidelines.
Several hypertension guidelines have removed beta-blockers from their previous position as first-choice drugs for the treatment of hypertension. However, this downgrading may not be justified by available evidence because beta-blockers lower blood pressure as effectively as other major antihypertensive drugs and have solid documentation in preventing cardiovascular complications. Suspected inconveniences of beta-blockers such as increased risk of depression or erectile dysfunction may have been overemphasized, while patients with chronic obstructive pulmonary disease or peripheral artery disease, that is, conditions in which their use was previously restricted, will benefit from beta-blocker therapy. Besides, evidence that from early to late phases, hypertension is accompanied by activation of the sympathetic nervous system makes beta-blockers pathophysiologically an appropriate treatment in hypertension. Beta-blockers have favorable effects on a variety of clinical conditions that may coexist with hypertension, making their use either as specific treatment or as co-treatment potentially common in clinical practice. Guidelines typically limit recommendations on specific beta-blocker use to cardiac conditions including angina pectoris, postmyocardial infarction, or heart failure, with little or no mention of the additional cardiovascular or noncardiovascular conditions in which these drugs may be needed or preferred. In the present narrative review, we focus on multiple additional diseases and conditions that may occur and affect patients with hypertension, often more frequently than people without hypertension, and that may favor the choice of beta-blocker. Notwithstanding, beta-blockers represent an in-homogenous group of drugs and choosing beta-blockers with documented effect in prevention and treatment of disease is important for first choice in guidelines.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Blood Pressure; Cardiology; Humans; Hypertension; Male
PubMed: 35378981
DOI: 10.1161/HYPERTENSIONAHA.122.19020