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European Annals of Otorhinolaryngology,... Nov 2011Infantile haemangioma (IH) is the most common tumour during early childhood. Although these benign lesions resolve spontaneously, up until recently laryngotracheal sites... (Review)
Review
Infantile haemangioma (IH) is the most common tumour during early childhood. Although these benign lesions resolve spontaneously, up until recently laryngotracheal sites of IH required invasive management. The dramatic efficacy of β-blockers on IH has radically changed the prognosis. Surgery is now no longer indicated as first-line therapy, but should only be performed for difficult, refractory cases, or in the presence of absolute contraindications to β-blockers. Long-term steroid therapy is also no longer indicated. Propranolol can be used as first-line, single-agent therapy.
Topics: Acebutolol; Adrenergic beta-Antagonists; Dose-Response Relationship, Drug; Hemangioma; Humans; Infant; Laryngeal Neoplasms; Laryngoscopy; Propranolol; Tracheal Neoplasms
PubMed: 21498145
DOI: 10.1016/j.anorl.2010.11.009 -
The American Journal of Cardiology Mar 1993Early studies of acute beta-blocking drug therapy, such as metoprolol and acebutolol, in patients with idiopathic dilated cardiomyopathy (IDC) and survivors of acute... (Review)
Review
Early studies of acute beta-blocking drug therapy, such as metoprolol and acebutolol, in patients with idiopathic dilated cardiomyopathy (IDC) and survivors of acute myocardial infarction were interpreted to have detrimental or, at best, neutral effects on cardiac and clinical hemodynamics. Subsequent trials of longer duration with metoprolol versus placebo in patients with IDC demonstrated an "exceptional response" to beta-blocker therapy in some individuals. Hemodynamics and patient demographic characteristics appear not to predict those patients who may or may not benefit. Controlled trials with newer beta-adrenoceptor modulating drugs--such as xamoterol, bucindolol, and carvedilol--have been equivocal in some situations. Xamoterol has been associated with progressive heart failure and increased sudden cardiac deaths, whereas bucindolol improved clinical heart failure symptoms and testing hemodynamic parameters, as did treatment with carvedilol, in patients with ischemic cardiomyopathy. The success of these agents in patients with congestive heart failure may be in their ability to modulate the excessive myocardial stimulation of the beta-adrenergic nervous system while benefitting the dynamics of the peripheral system.
Topics: Adrenergic beta-Antagonists; Cardiomyopathy, Dilated; Female; Hemodynamics; Humans; Male; Metoprolol; Middle Aged
PubMed: 8096675
DOI: 10.1016/0002-9149(93)90086-r -
Journal of Translational Medicine Aug 2018Major differences exist between men and women in both physiology and pathophysiology. Dissecting the underlying processes and contributing mechanisms of sex differences...
BACKGROUND
Major differences exist between men and women in both physiology and pathophysiology. Dissecting the underlying processes and contributing mechanisms of sex differences in health and disease represents a crucial step towards precision medicine. Considering the significant differences between men and women in the response to pharmacotherapies, our aim was to develop an in silico model able to predict sex-specific drug responses in a large-scale.
METHODS
For this purpose, we focused on cardiovascular effects because of their high morbidity and mortality. Our model predicted several drugs (including acebutolol and tacrine) with significant differences in the heart between men and women. To validate the sex-specific drug responses identified by our model, acebutolol was selected to lower blood pressure in spontaneous hypertensive rats (SHR), tacrine was used to assess cardiac injury in mice and metformin as control for a non-sex-specific response.
RESULTS
As our model predicted, acebutolol exhibited a stronger decrease in heart rate and blood pressure in female than male SHRs. Tacrine lowered heart rate in male but not in female mice, induced higher plasma cTNI level and increased cardiac superoxide (DHE staining) generation in female than male mice, indicating stronger cardiac toxicity in female than male mice. To validate our model in humans, we employed two Chinese cohorts, which showed that among patients taking a beta-receptor blocker (metoprolol), women reached significantly lower diastolic blood pressure than men.
CONCLUSIONS
We conclude that our in silico model could be translated into clinical practice to predict sex-specific drug responses, thereby contributing towards a more appropriate medical care for both men and women.
Topics: Acebutolol; Animals; Blood Pressure; China; Computer Simulation; Drug Therapy; Female; Heart; Heart Injuries; Heart Rate; Humans; Hypertension; Male; Metformin; Mice; Mice, Inbred C57BL; Middle Aged; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Sex Factors; Tacrine
PubMed: 30157868
DOI: 10.1186/s12967-018-1612-6 -
British Journal of Clinical Pharmacology Aug 2016Peripheral vasoconstriction has long been described as a vascular adverse effect of β-adrenoceptor blockers. Whether β-adrenoceptor blockers should be avoided in... (Comparative Study)
Comparative Study Meta-Analysis Review
AIM
Peripheral vasoconstriction has long been described as a vascular adverse effect of β-adrenoceptor blockers. Whether β-adrenoceptor blockers should be avoided in patients with peripheral vascular disease depends on pharmacological properties (e.g. preferential binding to β1 -adrenoreceptors or intrinsic sympathomimetic activity). However, this has not been confirmed in experimental studies. We performed a network meta-analysis in order to assess the comparative risk of peripheral vasoconstriction of different β-adrenoceptor blockers.
METHOD
We searched for randomized controlled trials (RCTs) including β-adrenoceptor blockers that were published in core clinical journals in the Pubmed database. All RCTs reporting peripheral vasoconstriction as an adverse effect of β-adrenoceptor blockers and controls were included. Sensitivity analyses were conducted including possibly confounding covariates (latitude, properties of the β-adrenoceptor blockers, e.g. intrinsic sympathomimetic activity, vasodilation, drug indication, drug doses). The protocol and the detailed search strategy are available online (PROSPERO registry CRD42014014374).
RESULTS
Among 2238 records screened, 38 studies including 57 026 patients were selected. Overall, peripheral vasoconstriction was reported in 7% of patients with β-adrenoceptor blockers and 4.6% in the control groups (P < 0.001), with heterogeneity among drugs. Atenolol and propranolol had a significantly higher risk than placebo, whereas pindolol, acebutolol and oxprenolol had not.
CONCLUSION
Our results suggest that β-adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to β1 -adrenoceptors. These findings challenge FDA and European recommendations regarding precautions and contra-indications of use of β-adrenoceptor blockers and suggest that β-adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with peripheral vascular disease.
Topics: Adrenergic beta-Antagonists; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic; Sympathomimetics; Vasoconstriction; Vasodilation
PubMed: 27085011
DOI: 10.1111/bcp.12980 -
British Journal of Clinical Pharmacology Feb 19761 The effects of beta-adrenoceptor blockade on the metabolic responses to isoprenaline have been studied in an in vitro system of isolated fat cells and in six normal... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1 The effects of beta-adrenoceptor blockade on the metabolic responses to isoprenaline have been studied in an in vitro system of isolated fat cells and in six normal subjects. 2 The inhibitory effects of varying concentrations of acebutolol, practolol and propranolol on free fatty acid (FFA) release produced by isoprenaline (10(-7) M) were compared in isolated fat cells prepared from rat epididymal adipose tissue. Acebutolol and practolol, at equimolar concentrations, showed a similar inhibitory effect whilst propranolol was approximately 100 times more potent then either drug. At 10(-5)M concentration of propranolol, lipolysis was virtually abolished whilst at the same molar concentration, acebutolol and practolol halved the response. 3 Six healthy volunteers received three successive 15 min intravenous isoprenaline challenges (0.03 mug kg-1 min-1) per individual experiment. The first acted as a control whilst the following two were given either after single oral doses of placebo, acebutolol or practolol. The mean (+/- s.e. mean) basal FFA level was 0.77 +/- 0.06 mE1/1 and subsequent resting values after the administration of placebo or beta-adrenoceptor blocker were not significantly different. 4 Acebutolol inhibited the respective mean rises in FFA, produced by both post-control isoprenaline challenges, by (mean +/- s.e. mean) 70 +/- 4% and 84% +/- 5%. The comparable figures for practolol were 33 +/- 15% and 24 +/- 20%. The higher serum concentration of acebutolol produced greater inhibition but correlation of log serum concentration of the drug with percentage inhibition of FFA rise did not achieve significance. 5 Administration of isoprenaline, acebutolol or practolol did not significantly alter serum glucose, triglyceride or cholesterol levels. 6 Acebutolol and practolol effectively blocked the isoprenaline-induced tachycardia. The degree of blockade produced by practolol was greater than its inhibitory effect on FFA release. The diatolic fall in blood pressure in response to isoprenaline was abolished by acebutolol suggesting that its beta-adrenoceptor blocking action encompasses peripheral vascular sites. The comparable effect with practolol was a partial inhibition of the diastolic fall.
Topics: Acebutolol; Adult; Animals; Blood Pressure; Fatty Acids, Nonesterified; Heart Rate; Humans; In Vitro Techniques; Isoproterenol; Lipid Metabolism; Male; Middle Aged; Placebos; Practolol; Propranolol; Rats
PubMed: 973938
DOI: 10.1111/j.1365-2125.1976.tb00586.x -
British Journal of Clinical Pharmacology Sep 1983Acebutolol was administered orally in a single dose of 200 mg to 17 individuals whose renal function varied markedly. The plasma half-life and elimination rate constant...
Acebutolol was administered orally in a single dose of 200 mg to 17 individuals whose renal function varied markedly. The plasma half-life and elimination rate constant for acebutolol showed a four-fold variation but these did not correlate with the degree of renal impairment. However, there was a good correlation between the renal clearance of creatinine and that of acebutolol (P less than 0.001). The half-life and elimination rate of the acetyl metabolite, diacetolol, were subject to 10-fold inter-individual variability which correlated significantly with the creatinine clearance and serum creatinine concentration. The AUC for the acetyl metabolite showed a 40-fold individual variation which also correlated with renal function. It is concluded that renal elimination is the principal route of excretion for diacetolol but not the parent compound, acebutolol.
Topics: Acebutolol; Acetylation; Adult; Biotransformation; Creatinine; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged
PubMed: 6626416
DOI: 10.1111/j.1365-2125.1983.tb02158.x -
The Cochrane Database of Systematic... 2001Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These... (Review)
Review
BACKGROUND
Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease.
OBJECTIVES
To assess the effect of cardioselective beta-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component.
SEARCH STRATEGY
A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to February, 2000. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language.
SELECTION CRITERIA
Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta-agonist administration, or the presence of asthma as defined by the American Thoracic Society.
DATA COLLECTION AND ANALYSIS
Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta-agonist given after the study drug.
MAIN RESULTS
Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta-agonist response compared to placebo, a response not seen with beta-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]).
REVIEWER'S CONCLUSIONS
Cardioselective beta-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should not be withheld from patients with mild-moderate reversible airway disease.
Topics: Acebutolol; Adrenergic beta-Antagonists; Asthma; Celiprolol; Female; Forced Expiratory Volume; Humans; Male; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Xamoterol
PubMed: 11406056
DOI: 10.1002/14651858.CD002992 -
British Journal of Clinical Pharmacology Nov 2010A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was... (Review)
Review
A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume-effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice.
Topics: Administration, Oral; Anti-Allergic Agents; Beverages; Biological Availability; Citrus; Citrus paradisi; Food-Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Organic Anion Transporters; Terfenadine
PubMed: 21039758
DOI: 10.1111/j.1365-2125.2010.03722.x -
Heliyon Oct 2023A straightforward approach for creating fast and novel potentiometric sensors that are modified with multi-walled nanotubes (MWCNTs) was described. The impact of the...
Fast and novel multiwalled carbon nanotubes decorated with metal oxide nanoparticles for potentiometric detection of a prohibited medication in sports acebutolol hydrochloride.
A straightforward approach for creating fast and novel potentiometric sensors that are modified with multi-walled nanotubes (MWCNTs) was described. The impact of the selective sensor's material was studied. The suggested sensors were successfully fabricated for instant and fast detection of the prohibited β-adrenoreceptor blocking agent acebutolol hydrochloride (AC) in commercial products. Acebutolol-phosphomolybdate (AC-PM) carbon paste sensor was formed by mixing AC and phosphomolybdic acid and graphite powder in the presence of -nitrophenyl octyl ether (-NPOE) as a plasticizing agent. The functionalized AC-PM-MWCNTs and AC-PM-MWCNTs-AlO nanocomposite sensors were prepared and all parameters affecting the sensors' potential responses have been investigated as well as the green synthesis of AlONPs has been characterized using various microscopic and spectroscopic techniques. AC-PM-MWCNTs and AC-PM-MWCNTs-AlO nanocomposite sensors demonstrated linearity of 1.0 × 10-1.0 × 10 and 1.0 × 10-1.0 × 10 mol L, respectively with regression equations -53.571x + 423.24 (r = 0.999) and -57.107x + 518.54 (r = 0.999). It also revealed excellent selectivity and sensitivity for the determination and quantification of AC. The developed potentiometric system was suitable for the determination of AC in bulk powder and commercial products.
PubMed: 37876475
DOI: 10.1016/j.heliyon.2023.e20997 -
British Journal of Clinical Pharmacology Nov 19811 The effects of single evening doses of the beta-adrenoceptor blocking agents propranolol (80 mg orally) and acebutolol (200 mg orally) on plasma levels throughout the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
1 The effects of single evening doses of the beta-adrenoceptor blocking agents propranolol (80 mg orally) and acebutolol (200 mg orally) on plasma levels throughout the night of prolactin, growth hormone, luteinising hormone, follicle stimulating hormone, cortisol and testosterone have been studied in seven healthy male volunteers. 2 Three way analysis of variance showed that acebutolol significantly reduced circulating levels of prolactin and follicle stimulating hormone, but did not alter the levels of the other hormones studied. 3 Propranolol significantly reduced follicle stimulating hormone and testosterone, and significantly increased circulating levels of cortisol, but caused no change in the other hormones studied. 4 Prolactin, luteinising hormone, testosterone and cortisol showed a significant variation with time indicating the existence of a diurnal rhythm in the pattern of their secretion. 5 There was a significant inter-subject variability in all the hormones studied. 6 There was a significant between-subject variation in response to both propranolol and acebutolol. 7 Different subjects showed significant variations with respect to time in prolactin, growth hormone and cortisol levels. 8 Neither propranolol nor acebutolol significantly altered the time course of secretion of any of the hormones studied. 9 Possible relationships of these beta-adrenoceptor blocker-induced changes in anterior pituitary and related hormones to the antihypertensive mechanism of acebutolol and propranolol are discussed.
Topics: Acebutolol; Adult; Follicle Stimulating Hormone; Growth Hormone; Humans; Hydrocortisone; Luteinizing Hormone; Male; Pituitary Hormones, Anterior; Prolactin; Propranolol; Sleep; Testosterone
PubMed: 6800389
DOI: 10.1111/j.1365-2125.1981.tb01298.x