Beta-Adrenergic Blocking Agents Research Articles

Application of UHPLC-QqQ-MS/MS Method for Quantification of Beta-Adrenergic Blocking Agents (β-Blockers) in Human Postmortem Specimens.

Betablockers are one of the most frequently used medications in cardiology. They can lead to fatal drops in blood pressure and heart rhythm disturbances. Death is functional, and poisoning with this group of drugs can be difficult to detect. The liquid-liquid extraction (LLE) method developed using ethyl acetate at pH 9 successfully identified 18 β-blockers in human blood. The method's limit of quantification (LOQ) was in the range of 0.1 to 0.5 ng/mL. No carryover of substances between samples was detected, and no interfering ion current signals were observed in the biological samples at the retention times of the compounds or internal standards. All compounds had a coefficient of determination (R2) above 0.995. Intraday and interday precision (RSD%) and accuracy (RE%) for low and high QC levels were within 1.7-12.3% and -14.4 to 14.1%, respectively. Very good recovery (80.0-119.6%) and matrix effect (±20.0%) values were achieved for all compounds. In addition, fragmentation spectra were collected for all the examined substances, and high-resolution spectra were presented for landiolol and metipranolol, because they are not available in commercial HRMS spectra databases. The developed method was applied in authentic postmortem samples.

Comment on Katsarelias, D., et al. "The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma-A Nation-Wide Swedish Population-Based Retrospective Register Study" Cancers 2020, 12, 3228.

We read the paper by Katsarelias et al. with great interest, regarding the effect of beta-adrenergic blocking agents on cutaneous melanoma [1]. However, the study presents some methodology biases that do not allow us to support the authors' conclusions. The paper suffers from the unification and evaluation of multiple registries, which do not provide essential data for any of the targets for research. Unlike studies in the literature [...].

Reply to Comment on Katsarelias, D., et al. "The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma-A Nation-Wide Swedish Population-Based Retrospective Register Study." Cancers 2020, 12, 3228.

We thank De Giorgi et al for their interest in our study, and for raising important and relevant questions [...].

The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma-A Nation-Wide Swedish Population-Based Retrospective Register Study.

Simple SummaryPrevious smaller studies have showed that a common heart medication, beta-blockers, potentially could reduce the risk of recurrence in patients with malignant melanoma and thereby increase survival. By combining different Swedish population-based registries, a total of 12,738 patients with melanoma were identified. Out of these patients 3702 had been prescribed beta-blockers and the remaining 9036 patients served as the control group. In a statistical analysis adjusting for known risk factors there was no effect of beta-blockers in reducing the risk of dying from melanoma. In conclusion, this population-based registry study could not verify the hypothesis that the use of beta blockers would improve survival in patients with melanoma.Previous studies have demonstrated an anti-tumoral effect of beta-adrenergic blocking agents on cutaneous melanoma (CM). The aim of this study was to investigate if beta-adrenergic blocking agents have an impact on survival in Swedish patients with melanoma. A population-based retrospective registry study including all patients diagnosed with a primary invasive melanoma between 2009 and 2013 was performed. Data from the Swedish Melanoma Register were linked to the Swedish Prescribed Drug Registry and the Swedish Cause of Death Register. Cox regression analyses including competing risk assessments were performed. There were 12,738 patients included, out of which 3702 were exposed to beta-blockers vs. 9036 non-exposed patients. Age, male sex, Breslow thickness, ulceration, and nodal status were independent negative prognostic factors for melanoma-specific survival (MSS). Adding beta-blockers to the analysis did not add any prognostic value to the model (HR 1.00, p = 0.98), neither when adjusting for competing risks (HR 0.97, p = 0.61). When specifically analyzing the use of non-selective beta-blockers, the results were still without statistical significance (HR 0.76, p = 0.21). In conclusion, this population-based registry study could not verify that the use of beta-adrenergic blocking agents improve survival in patients with melanoma.

Nurse-led Titration of Angiotensin Converting Enzyme Inhibitors and Beta-Adrenergic Blocking Agents for Patients with Heart Failure with Reduced Ejection Fraction: A Meta-Analysis

Nurse-led Titration of Angiotensin Converting Enzyme Inhibitors and Beta-Adrenergic Blocking Agents for Patients with Heart Failure with Reduced Ejection Fraction: A Meta-Analysis

Trends in the Care of Patients With Acute Myocardial Infarction at a University-Affiliated Veterans Afffairs Medical Center

Acute cardiac care of the veterans at Veterans Administration (VA) hospitals has been thought of as poor in quality. We examined the use of life-saving, evidence-based medical therapy in patients admitted with acute myocardial infarction to the University of Arkansas for Medical Sciences-affiliated VA Medical Center in Little Rock and compared the use of this therapy with other hospitals in Arkansas and in the rest of the nation. Use of life-saving medical therapy in 117 patients admitted with acute myocardial infarction from January 2002 to December 2002 was compared with the National Registry of Myocardial Infarction database for the identical period. Heparin/low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitors were used in 88% and 66% of patients, respectively. Aspirin, beta adrenergic-blocking agents, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) were used in 92%, 93%, 62%, and 79% of the patients, respectively. The use of these therapies was better than in similar patients in Arkansas (P < .001) and the United States as a whole (P < .01). Calcium-channel blockers were used in 16% of the patients. At a mean follow-up period of 1.5 years, use of beta blockers and aspirin had decreased, whereas the use of statins and ACE inhibitors/ARBs was unchanged. This study shows that patients with acute myocardial infarction admitted to this university-affiliated VA Medical Center receive evidence-based life-saving medical therapy more often than in the rest Arkansas or in the entire United States. More important, patients at this federal institution continue to receive life-saving medical therapy during follow-up. Better use of evidence-based therapy may be related to affiliation of this VA Medical Center with a teaching institution where board certified cardiologists are involved in short- and long-term care of these patients.

Heart failure therapy at the turn of the century.

Major changes in the treatment of heart failure have occurred in the last fifty years that have had a dramatic effect on its morbidity and mortality. Over two hundred years have passed since the demonstration of the benefit of digitalis in heart failure to the development of potent loop diuretics. The observation that vasodilators could improve both cardiac function and mortality led to the investigation of the Angiotensin Converting Enzyme Inhibitors (ACEI). Although these agents had significant vasodilator properties, their major benefit appears to be related to their ability to effect remodeling of the failing left ventricle. The most recent randomized clinical trials demonstrate that Beta Adrenergic Blocking agents can provide an incremental effect on both mortality and morbidity when added to therapy with ACEI. Although these agents have improved the outlook for the heart failure patient, they have had very little effect on the improvement of left ventricular function. Future research must be directed at methods to deal with this issue by either changing the contractile properties of the cardiomyocyte by pharmacologic or electrical therapy or by transplanting functional cells that can increase the number of functioning contractile units.

Long-term effects of beta-adrenergic blocking agent treatment on hemodynamic function and left ventricular remodeling in rats with experimental myocardial infarction: importance of timing of treatment and infarct size.

This study was designed to assess the long-term effects of a beta1-selective beta-adrenergic blocking agent on mortality, in vivo hemodynamic function, left ventricular volume and wall stress in post-myocardial infarction (MI) rats. Beta-blockers have shown beneficial results in clinical studies after MI. However, the underlying mechanism is not yet understood, and experimental studies have shown conflicting results. Bisoprolol (60 mg/kg body weight per day) was given 30 min or 14 days after MI or sham operation. The mortality rate was reduced only in early bisoprolol-treated rats (29% vs. 46% in untreated rats, p < 0.05). Heart rate was equally reduced in all treatment groups, and the maximal rate of rise of left ventricular systolic pressure (dP/dt(max)) decreased in sham rats and in rats with a small to moderate infarct size. Stroke volume index was unchanged in sham rats and in rats with a small to moderate infarct with early or late bisoprolol treatment and increased in rats with a large infarct in the late bisoprolol group. Left ventricular volume was increased by bisoprolol in sham rats and rats with a small infarct but not in rats with a large infarct. Treatments starting early (30 min) or late (14 days) after coronary artery ligation with bisoprolol increased left ventricular volume in sham rats and in rats with a small infarct but not in rats with a large infarct. Late bisoprolol treatment improved stroke volume index, and early bisoprolol treatment reduced diastolic wall stress, in rats with a large myocardial infarct. Thus, bisoprolol effects on remodeling and cardiac performance after myocardial infarction strongly depend on infarct size and timing of treatment. This finding may explain previous controversial results that did not consider infarct size and timing of treatment.

Adrenergic beta-blocking agents in congestive heart failure due to idiopathic dilated cardiomyopathy.

The use of Beta-blockers for treatment of chronic heart failure due to idiopathic dilated cardiomyopathy has now begun to be accepted among cardiologists after having been used sporadically for 19 years. Pooled data from several minor controlled trials performed during the last 13 years which have shown consistent improvement of myocardial function, specifically in patients with idiopathic dilated cardiomyopathy, have recently been confirmed by two major trials using the selective beta-blockers metoprolol (MDC trial) and bisoprolol (CIBIS trial). There was a decrease of 34% in the combined number of deaths and patients needing a heart transplantation (P = 0.058) in the MDC trial. Bisoprolol, as well as reducing the overall mortality significantly, was found, in a retrospective subgroup analysis, to reduce mortality in idiopathic dilated cardiomyopathy. The MDC trial showed improvement in ejection fraction by 7 units compared with placebo and 13 units compared with baseline after 12 months treatment (P < 0.0001). There was also an increase in exercise time compared with placebo at 12 months follow-up. There was a 39% reduction in the number of readmissions to hospital due to heart failure and arrhythmias (P < 0.04) and a 32% reduction in the CIBIS trial (P < 0.01). Possible mechanisms for improvement after beta-blockers are improvement in myocardial energetic balance, protection against calcium overload or normalization of myocardial catecholamine kinetics. The role of upregulation of beta-adrenergic receptors remains controversial since this could not be seen in the action of all beta-blockers. The question of whether mortality can be reduced remains unsolved and will require large prospective trials which are now in progress.

A New Approach for the Direct Resolution of Racemic Beta Adrenergic Blocking Agents by HPLC

Abstract Although beta-adrenergic blocking agents are a relatively new group of drugs, they have proven to be very useful in medical pharmacology. Since the successful introduction of propranolol (Inderal) a variety of analogous compounds have been developed. Most beta-blockers are racemic modifications and it is known that their enantiomers have different potencies and pharmacological effects. Hence, there has been considerable impetus for the production and study of the pure enantiomers. The chromatographic separation of these compounds has been dominated by the protein-based chiral stationary phases. Although selective, protein columns have limited capacity and stability. An efficient, alternative method has been found that does not suffer from the limitations of the protein phases. By using an unusual mobile phase consisting of a mixture of polar organic solvents in conjunction with the original native cyclodextrin bonded phase, the following compounds were resolved: propranolol, metoprolol, timolol, ...

Marked splenic hyperaemia during post-haemorrhagic hypotension in the rat, rabbit and cat.

1. The regulation of the splenic perfusion during normal and pathological conditions is incompletely understood. We studied the time course of splenic blood flow during the initial (0-24 h) development of haemorrhagic anaemia in awake and anaesthetized rats, as well as in awake rabbits and cats. Another group of rats had either normovolaemic anaemia or beginning polycythaemia. 2. The microsphere method was used to measure splenic blood flow. The awake rats were rendered anaemic either by a heavy (1.5% of body weight) or a moderate (0.7% of body weight) bleeding (hypovolaemia), by haemolysis (normovolaemia) or by bleeding (1.5% of body weight) followed by transfusion of autologous plasma (normovolaemia). Polycythaemia was induced with injections of erythropoietin. The anaesthetized rats as well as the awake rabbits and cats were also bled heavily (1.5% of body weight). 3. In awake rats, splenic blood flow increased to 215% of control within the first 5 min after bleeding. The perfusion declined nearly to baseline over the next 24 h. A similar, but less prominent splenic hyperaemia was detected in the awake rabbits and cats. However, this hyperaemic response was not detected in the normovolaemic, the polycythaemic or the anaesthetized and bled rats. 4. Administration of the adrenergic beta-blocking agent propranolol prior to bleeding significantly attenuated the splenic hyperaemia in the awake rats, while the alpha-blocking agent phentolamine or the cholinergic blocking agent atropine had no effect. 5. Concomitant with the initial increase in splenic perfusion, cardiac output increased to 123% of control in the awake, heavily bled rats. In the bled, anaesthetized rats cardiac output decreased to 91% of control 5 min after bleeding. A decrease in cardiac output to 64 and 70% of control was observed in the awake rabbits and cats, respectively. 6. Immediately following the bleeding, we noticed a substantial release of platelets from the rat spleen. 7. It appears that a heavy acute blood loss in awake rats, rabbits and cats elicits a marked reduction in splenic vascular tone, perhaps mediated by beta-adrenergic receptor activity. Anaesthesia abolished this response in rats. Possibly, the induced hypovolaemia triggered an accelerated release of platelets from the rat spleen, dependent on an augmented splenic blood flow.

Effect of a Beta-adrenergic Blocking Agent on Dental Anxiety

The effect of propranolol was studied on 23 dental phobics in a double-blind, placebo-controlled clinical trial involving actual dental treatment. The subjects were selected because they showed high physiological reactivity in the dental situation. Twelve subjects received the test drug and 11 subjects received the placebo at individualized doses of either 80 or 120 mg. A significant difference in self-reported anxiety at the injection phase of treatment and less overall pain intensity and aversiveness were observed for the propranolol as compared with the placebo group. No differences were detected for behavior ratings. Beta-adrenergic blocking agents may have utility for reducing anxiety in individuals fearful of dental treatment.

The Management of Performance Anxiety with Beta-Adrenergic Blocking Agents

Performance anxiety consists of several symptoms experienced in the context of public performance and is classified in DSM-III-R under social phobia. Performance anxiety must be distinguished from panic disorder, generalized social phobia, and generalized anxiety disorder. Performance anxiety symptoms can be detrimental to both performer and performance. These symptoms can be controlled by the judicious use of beta-adrenergic blocking agents. The use of beta-adrenergic blocking agents should be considered as part of a psychiatric stress-management program for these patients.

Myocardial Ischemia in Untreated Hypertensive Patients: Effect of a Single Small Oral Dose of a Beta-Adrenergic Blocking Agent

Myocardial Ischemia in Untreated Hypertensive Patients: Effect of a Single Small Oral Dose of a Beta-Adrenergic Blocking Agent

The Use of Beta-adrenergic Blocking Agents, IV Nitrates and Calcium Channel Blocking Agents following Acute Myocardial Infarction

number ofanimal experiments have suggested that agents which reduce the demand for oxygen by the ischemic myocardium can potentially reduce the extent of myocardial necrosis and consequently improve myocardial segmental function. In the last deeade, a number ofsuch pharmacologic agents have been investigated in man with the aim of reducing infarct size and consequently reducing morbidity and mortality. I shall review the available information on the effects of beta-adrenergic blocking agents, instituted intravenously (IV) and followed by long-term oral treatment, IV nitrates and oral calcium antagonists when administered to patients with acute myocardial infarction (MI). While the above agents reduce oxygen demand, they could affect a number of additional mechanisms (such as blocking the adverse effects of catecholamines on the myocardium by beta-blockers or blocking excess calcium entry during ischemia by calcium blockers), which could result in further benefit. In addition, some of these agents might have antiarrhythmia properties (eg, beta-blockers) which could theoretically prevent sudden death, or reduce wall stress (eg, beta-blockers or nitroglycerin) thereby preventing infarct expansion and myocardial rupture. Alternatively, these drugs also have the potential to worsen ischemia (excessive hypotension) or produce other adverse effects (conduction defects, etc). Therefore, the net benefit from these agents cannot be predicted from knowledge of mechanisms alone, but requires their assessment in careful, adequate-sized randomized controlled trials. BETA-ADRENERGIC BLOCKING AGENTS

Interaction of Beta-Adrenergic Blocking Agents with Human Low Density Lipoproteins Detected By EPR

Abstract The influence of beta-adrenergic agents on the structure and physico-chemical properties of model and natural membranes has been investigated by several autors. Knowledge of the mechanisms of the interaction between these pharmaca and membranes is necessary for a detailed description and further developrncnt of these pharmaca. One problem in understanding the pathways of pharmaca to the “target” membrane is the question of passing hydrophobic barriers (e.g., cell membranes). On the other hand, beta-adrenergic blocking agents have often been used in the treatment of coronary artery disease.

Long-term treatment of angina pectoris with carteolol: a new beta-adrenergic receptor blocking agent.

Seventy-two patients entered the treatment phase of an open, long-term, dose-ranging trial of carteolol in stable, exercise-induced angina pectoris. Patients were to be treated with progressive doses of carteolol (2.5, 5, 10, 20, 40, and 60 mg), given as a single daily oral dose. Thirty of the patients (42%) completed one year of treatment with carteolol as the sole antianginal therapy. The most frequent final carteolol doses were 20 mg and 40 mg once daily. Statistically significant improvements from baseline in exercise tolerance as reflected in time to onset of angina, time to the endpoint of exercise and time to the onset of 1 mm S-T segment change on ECG were observed in carteolol-treated patients. Exercise-induced increases in heart rate and double-product were significantly suppressed, compared to baseline, throughout the study. Resting heart rate and double-product were modestly decreased. Carteolol was shown to be effective and safe when administered on a long-term basis to patients with angina pectoris.

The retinal toxicity of befunolol and other adrenergic beta-blocking agents: Inhibition of phagocytic activity of cultured retinal pigment epithelial cells: by H. Matsuda, N. Yoshimura, M. Matsumura, and Y. Honda. Acta Ophthalmol 61: 343–352, 1983

The retinal toxicity of befunolol and other adrenergic beta-blocking agents: Inhibition of phagocytic activity of cultured retinal pigment epithelial cells: by H. Matsuda, N. Yoshimura, M. Matsumura, and Y. Honda. Acta Ophthalmol 61: 343–352, 1983

Effects of propranolol on colonic pressure in patients with irritable bowel syndrome.

The effect of propranolol on colonic motility was studied in 10 patients with irritable bowel syndrome. Colonic motility was recorded by pressure measurement 15-18 cm from the anus, and total contractile activity (kPa x min) simultaneously integrated. After rest, motility was recorded for 30 min after injection of saline (control period) and after injection of 5 mg propranolol intravenously. Administration of propranolol was followed by an increase in colonic motility in 9 out of the 10 patients. In one patient no change was observed. During the control period, total contractile activity was 7.7 +/- 18 (S.E.M.) kPa x min (58 +/- 14 mmHg x min), increasing after propranolol to 14.2 +/- 2.3 kPa x min (107 +/- 17 mmHg x min). The difference was significant (p less than 0.01). After propranolol, the colonic pressure waves regularly appeared for longer periods of time and had higher amplitudes than during control activity. Prolonged elevation of basal pressure with superimposed pressure waves was observed in two patients. This study shows that adrenergic beta-blocking agents enhance colonic motility in man. The results may explain abdominal symptoms such as pain and change in bowel habits appearing in patients treated with beta-blocking drugs.

The Role of Beta Adrenergic Blocking Agents in the Management of the Patient with Acute Myocardial Infarction

Patients with acute myocardial infarction who present with sympathetic overactivity, continuing chest pain, tachyarrhythmias, or hypertension may benefit from beta adrenergic blocking agent therapy. Studies have also suggested that these agents protect and salvage ischemic heart tissue and that long-term therapy may prevent reinfarction and sudden death.