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Pharmacotherapy Jul 2023Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate... (Review)
Review
Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.
Topics: Pregnancy; Female; Humans; Pregnancy Complications, Hematologic; Purpura, Thrombotic Thrombocytopenic; Pre-Eclampsia; Metoprolol; Intensive Care Units
PubMed: 37323102
DOI: 10.1002/phar.2837 -
MedComm Feb 2023In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure. The results...
In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure. The results demonstrated that bisoprolol improved the prognosis of chronic heart failure in comparison with carvedilol, and carvedilol exerted similar effects as metoprolol succinate and nebivolol and better effect than metoprolol tartrate (evidence levels: bisoprolol > carvedilol = metoprolol succinate = nebivolol > metoprolol tartrate; " > " means "prior to").
PubMed: 36628295
DOI: 10.1002/mco2.199 -
Journal of the American College of... Sep 2021Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting.
OBJECTIVES
The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19-associated ARDS.
METHODS
A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography.
RESULTS
Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO:FiO) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17).
CONCLUSIONS
In this pilot trial, intravenous metoprolol administration to patients with COVID-19-associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.
Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Aged; COVID-19; Critical Illness; Female; Humans; Injections, Intravenous; Male; Metoprolol; Middle Aged; Pandemics; Pilot Projects; Prospective Studies; Respiration, Artificial; SARS-CoV-2
PubMed: 34474731
DOI: 10.1016/j.jacc.2021.07.003 -
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 -
Cureus Aug 2023Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease and is a prevalent cause of sudden cardiac death (SCD). This study aims to establish the... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease and is a prevalent cause of sudden cardiac death (SCD). This study aims to establish the benefits and therapeutic value metoprolol or verapamil offer to patients who suffer from symptoms caused by HCM, with regard to resolving left ventricular outflow tract obstruction (LVOTO), as well as improving a patient's quality of life and reducing symptoms. We conducted a systematic review to find clinical studies that described the use of metoprolol or verapamil in the management of HCM. Three databases were analyzed for studies, PubMed, Google Scholar, and ScienceDirect. We discovered 6,260 potentially eligible records across all the databases. According to our eligibility criteria, we included four studies in this review. Metoprolol showed median left ventricular outflow tract (LVOT) gradients of 25 mm Hg versus 72 mm Hg (P = 0.007) at rest, 28 mm Hg versus 62 mm Hg (P < 0.001) at peak exercise, and 45 mm Hg versus 115 mm Hg (P < 0.001) post-exercise. Verapamil also showed a statistically significant increase in exercise capacity. Both drugs have been shown to be safe to use with a good side effect profile; however, metoprolol was better tolerated in the patient population that was tested in the studies collected. In this study, metoprolol was effective in reducing LVOT and improving the quality of life in patients, while verapamil showed variable effects on both exercise capacity and baseline hemodynamics.
PubMed: 37565181
DOI: 10.7759/cureus.43197 -
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 Medical Letter on Drugs and... Jan 2024
Topics: Humans; Atrial Fibrillation
PubMed: 38180321
DOI: 10.58347/tml.2024.1693a -
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 -
British Journal of Clinical Pharmacology Jun 2023Infusion of lipid emulsion for drug overdose arose as a treatment for local anaesthetic systemic toxicity (LAST) initially based on laboratory results in animal models...
Infusion of lipid emulsion for drug overdose arose as a treatment for local anaesthetic systemic toxicity (LAST) initially based on laboratory results in animal models with the subsequent support of favourable case reports. Following successful translation to the clinic, practitioners also incorporated lipid emulsion as a treatment for non-local anaesthetic toxicities but without formal clinical trials. Recent clinical trials demonstrate a benefit of lipid emulsion in antipsychotic, pesticide, metoprolol and tramadol overdoses. Formal trials of lipid emulsion in LAST may never occur, but alternative analytic tools indicate strong support for its efficacy in this indication; for example, lipid emulsion has obviated the need for cardiopulmonary bypass in most cases of LAST. Herein, we describe the pre-clinical support for lipid emulsion, evaluate the most recent clinical studies of lipid emulsion for toxicity, identify a possible dose-based requirement for efficacy and discuss the limitations to uncontrolled studies in the field.
Topics: Animals; Emulsions; Xenobiotics; Drug Overdose; Anesthetics, Local; Tramadol
PubMed: 36454165
DOI: 10.1111/bcp.15620