-
Clinical Advances in Periodontics Mar 2019Pemphigus vulgaris (PV) is a relatively rare, potentially life-threatening autoimmune disease that, in most cases, has an unknown etiology. Medications for hypertension...
INTRODUCTION
Pemphigus vulgaris (PV) is a relatively rare, potentially life-threatening autoimmune disease that, in most cases, has an unknown etiology. Medications for hypertension have been linked to the onset and exacerbation of PV-like symptoms. The diagnosis of medication-related PV can be challenging because it has an identical appearance to the clinical and histologic appearance of idiopathic PV and cases may not resolve after discontinuation of the drug.
CASE PRESENTATION
We present a case of an elderly patient with gingival and cutaneous erosions, who underwent several medical and dental consultations without an appropriate diagnosis. After biopsy and a thorough review of her medical history, metoprolol was suspected as the offending agent. After consulting with her cardiologist, metoprolol was discontinued, and a complete resolution of all lesions resulted.
CONCLUSIONS
To our knowledge, the current case is the first reported case of metoprolol-induced PV in the English-language literature. As such, it highlights the potential of medication involvement in some immune-mediated diseases. Because the oral mucosa is often the first site of involvement in PV, knowledge of drug-related PV is crucial in the diagnosis, treatment, and management of dental patients.
Topics: Aged; Antihypertensive Agents; Biopsy; Female; Humans; Metoprolol; Mouth Mucosa; Pemphigus
PubMed: 31490034
DOI: 10.1002/cap.10044 -
Journal of the American College of... Apr 2022The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood.
OBJECTIVES
This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM.
METHODS
This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest.
RESULTS
No treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008).
CONCLUSIONS
In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).
Topics: Cardiomyopathy, Hypertrophic; Hemodynamics; Humans; Metoprolol; Mitral Valve Insufficiency; Stroke Volume
PubMed: 35450573
DOI: 10.1016/j.jacc.2022.02.024 -
European Heart Journal Dec 2020
Topics: Adrenergic beta-Antagonists; Humans; Inflammation; Metoprolol; Reperfusion Injury
PubMed: 33210123
DOI: 10.1093/eurheartj/ehaa764 -
JACC. Clinical Electrophysiology Oct 2023Both selective and nonselective beta-blockers are used to treat patients with heart failure (HF). However, the data on the association of beta-blocker type with risk of...
BACKGROUND
Both selective and nonselective beta-blockers are used to treat patients with heart failure (HF). However, the data on the association of beta-blocker type with risk of atrial arrhythmia and ventricular arrhythmia (VA) in HF patients with a primary prevention implantable cardioverter-defibrillator (ICD) are limited.
OBJECTIVES
This study sought to evaluate the effect of metoprolol vs carvedilol on the risk of atrial tachyarrhythmia (ATA) and VA in HF patients with an ICD.
METHODS
This study pooled primary prevention ICD recipients from 5 landmark ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID). Fine and Gray multivariate regression models, stratified by study, were used to evaluate the risk of ATA, inappropriate ICD shocks, and fast VA (defined as ventricular tachycardia ≥200 beats/min or ventricular fibrillation) by beta-blocker type.
RESULTS
Among 4,194 patients, 2,920 (70%) were prescribed carvedilol and 1,274 (30%) metoprolol. The cumulative incidence of ATA at 3.5 years was 11% in patients treated with carvedilol vs 15% in patients taking metoprolol (P = 0.003). Multivariate analysis showed that carvedilol treatment was associated with a 35% reduction in the risk of ATA (HR: 0.65; 95% CI: 0.53-0.81; P < 0.001) when compared to metoprolol, and with a corresponding 35% reduction in the risk of inappropriate ICD shocks (HR: 0.65; 95% CI: 0.47-0.89; P = 0.008). Carvedilol vs metoprolol was also associated with a 16% reduction in the risk of fast VA. However, these findings did not reach statistical significance (HR: 0.84; 95% CI: 0.70-1.02; P = 0.085).
CONCLUSIONS
These findings suggests that HF patients with ICDs on carvedilol treatment experience a significantly lower risk of ATA and inappropriate ICD shocks when compared to treatment with metoprolol.
Topics: Humans; Metoprolol; Carvedilol; Defibrillators, Implantable; Atrial Fibrillation; Adrenergic beta-Antagonists; Heart Failure; Tachycardia, Ventricular
PubMed: 37656097
DOI: 10.1016/j.jacep.2023.06.009 -
Pharmacogenomics Jun 2023Few genome-wide association studies (GWASs) have been conducted to identify predictors of drug concentrations. The authors therefore sought to discover the...
Few genome-wide association studies (GWASs) have been conducted to identify predictors of drug concentrations. The authors therefore sought to discover the pharmacogenomic markers involved in metoprolol pharmacokinetics. The authors performed a GWAS of a cross-sectional study of 993 patients from the Montreal Heart Institute Biobank taking metoprolol. A total of 391 and 444 SNPs reached the significance threshold of 5 × 10 for metoprolol and α-OH-metoprolol concentrations, respectively. All were located on chromosome 22 at or near the gene, encoding CYP450 2D6, metoprolol's main metabolizing enzyme. The results reinforce previous findings of the importance of the locus for metoprolol concentrations and confirm that large biobanks can be used to identify genetic determinants of drug pharmacokinetics at a GWAS significance level.
Topics: Humans; Metoprolol; Genome-Wide Association Study; Cytochrome P-450 CYP2D6; Pharmacogenetics; Cross-Sectional Studies
PubMed: 37307170
DOI: 10.2217/pgs-2023-0067 -
The New England Journal of Medicine Jun 2021
Topics: Anti-Arrhythmia Agents; Electrocardiography; Humans; Male; Metoprolol; Middle Aged; Speech; Tachycardia, Supraventricular
PubMed: 34080808
DOI: 10.1056/NEJMicm2030596 -
BMC Pulmonary Medicine Nov 2023Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms.
OBJECTIVE
We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH.
METHODS
ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ).
RESULTS
We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45-5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77-1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32-6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61).
CONCLUSIONS
In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.
Topics: Humans; Adrenergic beta-Antagonists; Disease Progression; Metoprolol; Morbidity; Pulmonary Disease, Chronic Obstructive
PubMed: 37946165
DOI: 10.1186/s12890-023-02748-2 -
Pharmacological Research Aug 2019Heart rate is an important factor in coronary artery disease and its manifestations, and as such has been considered as a possible target for therapy. Although in... (Review)
Review
Heart rate is an important factor in coronary artery disease and its manifestations, and as such has been considered as a possible target for therapy. Although in epidemiological, and in less degree, in clinical studies derived indications of a possible pathogenetic role of heart rate in major cardiac diseases, clinical trials did not provided any strong evidence. However, even as a simple risk marker, remains important in the treatment of coronary artery disease and heart failure. Beta-blockers are the drugs most frequently used for heart rate control. However, recent studies constantly find insufficient effectiveness of beta-blockers in heart rate control and go further to question their efficacy on outcomes, making clear the need for an additional therapy. Ivabradine, a pure heart rate inhibitor, added to classic beta-blocker treatment represent the new therapeutic option in stable coronary disease and heart failure.
Topics: Adrenergic beta-Antagonists; Animals; Cardiovascular Agents; Coronary Artery Disease; Drug Combinations; Heart Rate; Humans; Ivabradine; Metoprolol
PubMed: 31108185
DOI: 10.1016/j.phrs.2019.104279 -
Journal of Hazardous Materials Feb 2023The recalcitrant β-blockers have been widely detected in aquatic environments up to several hundred μg/L, which are major contributors to β1 antagonistic activities...
The recalcitrant β-blockers have been widely detected in aquatic environments up to several hundred μg/L, which are major contributors to β1 antagonistic activities in wastewater. Their biodegradation mechanisms remain obscure, hindering the development of efficient removal techniques. This study constructed the biodegradation pathways for three typical β-blockers, namely atenolol, metoprolol, and propranolol, assessed the toxicity of their major biotransformation products, and identified the key enzyme catalyzing the O-dealkylation reaction leading to pollutant mineralization. Atenolol and metoprolol degradation was more efficient than that of propranolol by activated sludge, producing metoprolol acid (MTPA) as a major intermediate. Hydrogenophaga sp. YM1 isolated from activated sludge possess the α-ketoglutarate dependent dioxygenase (TfdA) responsible for O-dealkylation of MTPA and propranolol, producing 4-hydroxyphenylacetic acid (4-HPA) that can be further degraded and ultimately enters the TCA cycle. The role of TfdA was verified by proteomics, enzyme stimulation/inhibition tests, and gene knockout experiments. Molecular docking suggests its different interactions with MTPA and propranolol. Acetate facilitated the degradation of β-blockers efficiently. The results may shed light on enhanced biological removals of broader β-blockers and their transformation products in the environment.
Topics: Wastewater; Propranolol; Metoprolol; Sewage; Atenolol; Molecular Docking Simulation; Adrenergic beta-Antagonists
PubMed: 36417780
DOI: 10.1016/j.jhazmat.2022.130338 -
Pharmacology Research & Perspectives Aug 2019The aim of this study was to evaluate the pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology by reviewing single-dose and steady-state... (Review)
Review
The aim of this study was to evaluate the pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology by reviewing single-dose and steady-state pharmacokinetic studies from the literature. PubMed was searched for pharmacokinetic studies of beta-adrenergic blocking agents, both single-dose and steady-state studies. The studies included reported maximum plasma concentration (C) and/or area under the concentration curve (AUC). The coefficient of variation (CV%) was calculated for all studies, and a CV% <40% was considered low or moderate variability, and a CV% >40% was considered high variability. The C and AUC were reported a total of 672 times in 192 papers. Based on AUC, metoprolol, propranolol, carvedilol, and nebivolol showed high pharmacokinetic variability (highest first), whereas bisoprolol, atenolol, sotalol, labetalol, nadolol, and pindolol showed low to moderate variability (lowest first). We have shown a high interindividual pharmacokinetic variability that varies markedly in different beta-adrenergic blocking agents; the extreme being steady state ratios as high as 30 in metoprolol. A more personalized approach to the medical treatment of patients may be obtained by combining known pharmacokinetic information about variability, pharmaco-genetics and -dynamics, and patient characteristics, to avoid adverse events or lack of treatment effect.
Topics: Adrenergic beta-Antagonists; Area Under Curve; Biological Availability; Carvedilol; Healthy Volunteers; Humans; Male; Metoprolol; Propranolol
PubMed: 31338197
DOI: 10.1002/prp2.496