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1.
PLoS One ; 17(4): e0265497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35385506

RESUMO

BACKGROUND: Blood pressure (BP) elevations are commonly treated in hospitalized patients; however, treatment is not guideline directed. Our objective was to assess BP response to commonly prescribed antihypertensives after the development of severe inpatient hypertension (HTN). METHODS: This is a cohort study of adults, excluding intensive care unit patients, within a single healthcare system admitted for reasons other than HTN who developed severe HTN (systolic BP>180 or diastolic BP >110 mmHg at least 1 hour after admission). We identified the most commonly administered antihypertensives given within 6 hours of severe HTN (given to >10% of treated patients). We studied the association of treatment with each antihypertensive vs. no treatment on BP change in the 6 hours following severe HTN development using mixed-effects model after adjusting for demographics and clinical characteristics. RESULTS: Among 23,147 patients who developed severe HTN, 9,166 received antihypertensive treatment. The most common antihypertensives given were oral metoprolol (n = 1991), oral amlodipine (n = 1812), oral carvedilol (n = 1116), IV hydralazine (n = 1069) and oral hydralazine (n = 953). In the fully adjusted model, treatment with IV hydralazine led to 13 [-15.9, -10.1], 18 [-22.2, -14] and 11 [-14.1, -8.3] mmHg lower MAP, SBP, and DBP in the 6 hours following severe HTN development compared to no treatment. Treatment with oral hydralazine and oral carvedilol also resulted in significantly lower BPs in the 6 hours following severe HTN development (6 [-9.1, -2.1 and -7 [-9.1, -4.2] lower MAP, respectively) compared to no treatment. Receiving metoprolol and amlodipine did not result in a drop in BP compared to no treatment. CONCLUSION: Among commonly used antihypertensives, IV hydralazine resulted in the most significant drop in BP following severe HTN, while metoprolol and amlodipine did not lower BP. Further research to assess the effect of treatment on clinical outcomes and if needed which antihypertensives to administer are necessary.


Assuntos
Anti-Hipertensivos , Hipertensão , Adulto , Anlodipino/farmacologia , Pressão Sanguínea , Carvedilol/farmacologia , Estudos de Coortes , Humanos , Hidralazina/farmacologia , Hidralazina/uso terapêutico , Pacientes Internados , Metoprolol/farmacologia , Metoprolol/uso terapêutico
2.
J Am Coll Cardiol ; 79(16): 1565-1575, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35450573

RESUMO

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).


Assuntos
Cardiomiopatia Hipertrófica , Insuficiência da Valva Mitral , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/tratamento farmacológico , Hemodinâmica/fisiologia , Humanos , Metoprolol/farmacologia , Metoprolol/uso terapêutico , Insuficiência da Valva Mitral/complicações , Volume Sistólico/fisiologia
3.
J Healthc Eng ; 2022: 7340992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35449861

RESUMO

In China, the incidence of arrhythmia has also increased to approximately 20% of all cardiovascular diseases. The incidence of cardiovascular diseases in China has certain characteristics, which are generally low in the south and high in the north, and they tend to be younger and growing. Permanent pacemaker implantation is currently the most effective means of treating arrhythmia and preventing sudden death. To explore the clinical application value of metoprolol in patients after permanent pacemaker implantation. Ninety patients with permanent dual-chamber pacemaker implantation in our hospital are selected and divided into a metoprolol group and a control group according to whether metoprolol is used one week after the operation and 45 patients in each group. After one postoperative week, the LVEF%, LVEDd, LAD, and E/A of the metoprolol and the control groups had no statistically significant differences (p > 0.05). Twelve months postoperatively, the E/A of the metoprolol group is higher than that of the control group (p < 0.05), and LVEDd and LAD are lower than those of the control group (P < 0.05). The NT-proBNP and hs-CRP levels between the metoprolol and control groups had no significant differences (p > 0.05) in the values recorded immediately postoperatively. The NT-proBNP of the metoprolol group is lower than that of the control group (p < 0.05) at 12 months following pacemaker implantation. At one week after surgery, QTd, Pd, and Tp-Te are not significantly different (P > 0.05) between the metoprolol group and the control group, whereas the QTd and Pd times in the metoprolol group are lower than those in the control group (p < 0.05) at the 12-month follow-up. At one week postoperatively, the SDNN, SDANN, and RMSSD between the metoprolol and control groups did not show any statistically significant differences (p > 0.05). The SDANN of the metoprolol group is higher than that in the control group (p < 0.05) in the 12-month evaluation. One week after the operation, the serum IL-6 and TNF-α levels are not significantly different between the metoprolol and control groups (p > 0.05). At 12 months after surgery, the serum IL-6 and TNF-α levels in the metoprolol group are lower than those in the control group (p < 0.05). The incidence of adverse events in the metoprolol group is 9.30% lower than 26.83% in the control group within 12 months after the operation (p < 0.05). The use of metoprolol in patients with permanent pacemaker implantation after surgery can reduce the expansionary remodeling of the left atrium and have less impact on the QT-dispersion and Pd time.


Assuntos
Doenças Cardiovasculares , Marca-Passo Artificial , Arritmias Cardíacas , Humanos , Interleucina-6 , Metoprolol/uso terapêutico , Fator de Necrose Tumoral alfa
4.
Sci Rep ; 12(1): 5279, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35347168

RESUMO

ß-blocker therapy has been positively associated with improved survival in patients undergoing oncologic colorectal resection. This study investigates if the type of ß-blocker used affects 90-day postoperative mortality following colon cancer surgery. The study was designed as a nationwide retrospective cohort study including all adult (≥ 18 years old) patients with ongoing ß-blocker therapy who underwent elective and emergency colon cancer surgery in Sweden between January 1, 2007 and December 31, 2017. Patients were divided into four cohorts: metoprolol, atenolol, bisoprolol, and other beta-blockers. The primary outcome of interest was 90-day postoperative mortality. A Poisson regression model with robust standard errors was used, while adjusting for all clinically relevant variables, to determine the association between different ß-blockers and 90-day postoperative mortality. A total of 9254 patients were included in the study. There was no clinically significant difference in crude 90-day postoperative mortality rate [n (%)] when comparing the four beta-blocker cohorts metoprolol, atenolol, bisoprolol and other beta-blockers. [97 (1.8%) vs. 28 (2.0%) vs. 29 (1.7%) vs. 11 (1.2%), p = 0.670]. This remained unchanged when adjusting for relevant covariates in the Poisson regression model. Compared to metoprolol, there was no statistically significant decrease in the risk of 90-day postoperative mortality with atenolol [adj. IRR (95% CI): 1.45 (0.89-2.37), p = 0.132], bisoprolol [adj. IRR (95% CI): 1.45 (0.89-2.37), p = 0.132], or other beta-blockers [adj. IRR (95% CI): 0.92 (0.46-1.85), p = 0.825]. In patients undergoing colon cancer surgery, the risk of 90-day postoperative mortality does not differ between the investigated types of ß-adrenergic blocking agents.


Assuntos
Antagonistas Adrenérgicos beta , Neoplasias do Colo , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Bisoprolol/efeitos adversos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Humanos , Metoprolol/uso terapêutico , Estudos Retrospectivos
5.
Gen Comp Endocrinol ; 321-322: 114032, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35331741

RESUMO

The current study was aimed to determine the possible effects of the central adrenergic and dopaminergic receptors in neuromedin S (NMS)-induced hypophagia in neonatal layer-type chickens. In the first experiment, control solution, and NMS (0.25, 0.5, and 1 nmol), were injected (intracerebroventricular (ICV)) in chickens. In the second experiment, birds were injected with a control solution,SCH23390 (D1receptor antagonist, 5 nmol), NMS (1 nmol), and a combination of the SCH23390 + NMS. Experiments 3-11 were similar to experiment 2, except that chickens were injected withAMI-193 (D2receptor antagonist, 5 nmol), NGB2904(D3receptor antagonist, 6.4 nmol), L-741,742(D4receptor antagonist, 6 nmol), 6-OHDA(6-hydroxydopamine, 2.5 nmol),Prazosin(α1receptor antagonist, 10 nmol),Yohimbine(α2receptor antagonist, 13 nmol),Metoprolol(ß1receptor antagonist receptor, 24 nmol),ICI 118,551 (ß2receptor antagonist, 5 nmol),SR 59230R (ß3 receptor antagonist, 20 nmol) instead ofSCH23390. Then, cumulative food intake was recorded at 30, 60, and 120 min following the injection. According to the results, food intake was significantly decreased after ICV injection of NMS in a dose -dependent manner (P < 0.05). Also, the co-injection of the SCH23390 + NMS significantly attenuated NMS-induced hypophagia (P < 0.05). The co-administration of AMI-193 + NMS significantly reduced NMS- induced hypophagia (P < 0.05). In addition, the co-injection of ICI 118,551 + NMS and 6-OHDA + NMS considerably decreased NMS-induced food consumption (P < 0.05). However, NGB2904, L-741742, Prazosin, Yohimbine, Metoprolol and SR 59230R had no effect on hypophagia induced by NMS (P > 0.05). These results demonstrated thatNMS- induced hypophagia might be mediated by D1/D2 dopaminergic andß2adrenergic receptors in neonatal layer-type chickens.


Assuntos
Galinhas , Ingestão de Alimentos , Adrenérgicos/farmacologia , Animais , Animais Recém-Nascidos , Comportamento Alimentar , Metoprolol/farmacologia , Neuropeptídeos , Oxidopamina/farmacologia , Prazosina/farmacologia , Receptores Dopaminérgicos , Ioimbina/farmacologia
6.
Int J Pharm ; 617: 121598, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35202728

RESUMO

Continuous manufacturing (CM) has been used to produce several immediate release drug products. No extended-release (ER) product manufactured employing CM technology has been approved yet. This study investigated the critical aspects of switching from the batch mode of high shear granulation to the continuous operation of twin-screw granulation for extended-release tablets. Metoprolol succinate ER tablets was used as a model ER formulation for this purpose. A central composite design (CCD) was employed to determine the effects of high shear granulator (HSG) parameters, namely impeller speed, granulation time, and binder liquid feeding rate, on the critical granulation characteristics important for product performance. These critical granulation characteristics served as a guide for switching from the batch processing to the continuous operation for achieving the same breaking strength and dissolution for this ER metoprolol tablets. The granulation time was the most critical factor affecting the bulk properties of granules which contributed to tablet dissolution. The higher density and lower compressibility of granules were attained at the longest granulation time of 5.4 min with the fastest liquid feeding rate of 75 g/min. The granules' density was the primary factor negatively affecting the dissolution of metoprolol tablets. However, the breaking strength of tablets confounded the effect of granules density on metoprolol dissolution. Switching the processing parameters of high shear granulation to twin-screw granulation achieved similar dissolution profiles (F2 greater than 50). The screw speed was not found to affect bulk properties of granules. The root cause of granulation failures in twin-screw granulation, such as premature consolidation, excessive swelling, poor cohesion, inconsistent shearing effects, and formation of deformed agglomerates, were identified. In conclusion, the use of critical granulation characteristics through a performance-based approach of ER tablets facilitated the switching of manufacturing of an ER formulation form batch to continuous operation.


Assuntos
Excipientes , Metoprolol , Composição de Medicamentos , Tamanho da Partícula , Solubilidade , Comprimidos , Tecnologia Farmacêutica
7.
Clin Transl Sci ; 15(4): 1063-1073, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35122397

RESUMO

Large, observational genetic studies are commonly used to identify genetic factors associated with diseases and disease-related traits. Such cohorts have not been commonly used to identify genetic predictors of drug dosing or concentrations, perhaps because of the heterogeneity in drug dosing and formulation, and the random timing of blood sampling. We hypothesized that large sample sizes relative to traditional pharmacokinetic studies would compensate for this variability and enable the identification of pharmacogenetic predictors of drug concentrations. We performed a cross-sectional, proof-of-concept association study to replicate the well-established association between metoprolol concentrations and CYP2D6 genotype-inferred metabolizer phenotypes in participants from the Montreal Heart Institute Hospital Cohort undergoing metoprolol therapy. Plasma concentrations of metoprolol and α-hydroxymetoprolol (α-OH-metoprolol) were measured in samples collected randomly regarding the previous metoprolol dose. A total of 999 individuals were included. The metoprolol daily dose ranged from 6.25 to 400 mg (mean 84.3 ± 57.1 mg). CYP2D6-inferred phenotype was significantly associated with both metoprolol and α-OH-metoprolol in unadjusted and adjusted models (all p < 10-14 ). Models for metoprolol daily dose showed consistent results. Our study suggests that randomly drawn blood samples from biobanks can serve as a new approach to discover genetic associations related to drug concentrations and dosing, with potentially broader implications for genomewide association studies on the pharmacogenomics of drug metabolism.


Assuntos
Citocromo P-450 CYP2D6 , Metoprolol , Estudos Transversais , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Genótipo , Humanos , Metoprolol/farmacocinética , Fenótipo
8.
Sci Rep ; 12(1): 2168, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140291

RESUMO

Aging, polypharmacy (concurrent use of ≥ 5 medications), and functional impairment are global healthcare challenges. However, knowledge of the age/sex-specific effects of polypharmacy is limited, particularly on daily physical activities. Using continuous monitoring, we demonstrated how polypharmacy with high Drug Burden Index (DBI-cumulative anticholinergic/sedative exposure) affected behaviors over 23 h in male/female, young/old mice. For comparison, we also evaluated how different drug regimens (polypharmacy/monotherapy) influenced activities in young mice. We found that after 4 weeks of treatment, high DBI (HDBI) polypharmacy decreased exploration (reduced mean gait speed and climbing) during the habituation period, but increased it during other periods, particularly in old mice during the transition to inactivity. After HDBI polypharmacy, mean gait speed consistently decreased throughout the experiment. Some behavioral declines after HDBI were more marked in females than males, indicating treatment × sex interactions. Metoprolol and simvastatin monotherapies increased activities in young mice, compared to control/polypharmacy. These findings highlight that in mice, some polypharmacy-associated behavioral changes are greater in old age and females. The observed diurnal behavioral changes are analogous to drug-induced delirium and sundowning seen in older adults. Future mechanistic investigations are needed to further inform considerations of age, sex, and polypharmacy to optimize quality use of medicines.


Assuntos
Envelhecimento , Comportamento Animal , Ritmo Circadiano , Locomoção , Polimedicação , Fatores Etários , Animais , Antagonistas Colinérgicos/administração & dosagem , Comportamento Exploratório , Feminino , Hipnóticos e Sedativos/administração & dosagem , Masculino , Metoprolol/administração & dosagem , Camundongos , Fatores Sexuais , Sinvastatina/administração & dosagem
9.
J Hypertens ; 40(5): 1019-1029, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35202021

RESUMO

OBJECTIVE: Nonvasodilatory beta blockers are associated with inferior cardiovascular event reduction compared with other antihypertensive classes, and there is uncertainty about first-line use of beta blockers for hypertension in guidelines. The third generation vasodilatory beta blocker nebivolol has unique beneficial effects on central and peripheral vasculature. Our objective was to compare longitudinal cardiovascular outcomes of hypertensive patients taking nebivolol with those taking the nonvasodilatory beta blockers metoprolol and atenolol. METHODS: We performed a retrospective cohort analysis of hypertensive adults in the University of Colorado health system, without preceding diagnosis of cardiovascular or cerebrovascular disease. The primary outcome was composite incident heart failure, stroke, myocardial infarction, angina, or coronary revascularization. Mahalanobis 1:2 distance matching and Cox proportional hazards regression was used. Matching and regression variables included baseline demographics, socioeconomic factors, medical insurance type, prescribing provider type, cardiovascular risk factors, Charlson comorbidity index, other medications, and follow-up duration. RESULTS: After matching, patients were predominantly women (54%, 3085 of 5705) and non-Hispanic Caucasian (79%, 4534 of 5705), with median age of 58. In matched Cox regression analysis, nebivolol was associated with 17% reduction in incident cardiovascular events compared with all nonvasodilatory beta blockers [hazard ratio 0.83, 95% confidence interval (CI) 0.74-0.94, P  = 0.004], and 24% reduction compared with metoprolol (hazard ratio 0.76, CI 0.66-0.87, P = 0.0001). CONCLUSION: The vasodilatory beta blocker nebivolol was associated with reduced incident cardiovascular events compared with nonvasodilatory beta blockers. Additional study of other beta blockers is necessary to determine if this is a vasodilatory beta blocker class effect or is specific to nebivolol. GRAPHICAL ABSTRACT: http://links.lww.com/HJH/B916.


Assuntos
Hipertensão , Metoprolol , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Metoprolol/uso terapêutico , Nebivolol/uso terapêutico , Estudos Retrospectivos
11.
J Am Soc Mass Spectrom ; 33(2): 304-314, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35040644

RESUMO

Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic applications due to its simplicity, rapid analysis, and capability of reducing matrix effects for complex samples. To further promote the adoption of SPME-MS based analysis and expand its application scope calls for efficient and convenient interfaces that couple the SPME sample handling with the efficient analyte ionization for MS. Here, we report a novel interface that integrates both the desorption and the ionization steps in one device based on the capillary vibrating sharp-edge spray ionization (cVSSI) method. We demonstrated that the cVSSI is capable of nebulizing liquid samples in a pulled-tip glass capillary with a battery powered function generator. The cVSSI device allows the insertion of a SPME probe into the spray capillary for desorption and then direct nebulization of the desorption solvent in situ. With the integrated interface, we have demonstrated rapid MS analysis of drug compounds from serum samples. Quantitative determination of various drug compounds including metoprolol, pindolol, acebutolol, oxprenolol, capecitabine, and irinotecan was achieved with good linearity (R2 = 0.97-0.99) and limit of detection ranging from 0.25 to 0.59 ng/mL without using a high voltage source. Only 3.5 µL of desorption solvent and 3 min desorption time were needed for the present method. Overall, we demonstrated a portable SPME-MS interface featuring high sensitivity, short analysis time, small footprint, and low cost, which makes it an attractive method for many applications requiring sample cleanup including drug compound monitoring, environmental sample analysis, and forensic sample analysis.


Assuntos
Microextração em Fase Sólida/instrumentação , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Carbamazepina/química , Desenho de Equipamento , Limite de Detecção , Metoprolol/química , Pindolol/química , Sensibilidade e Especificidade , Soroalbumina Bovina/química
13.
Ann Vasc Surg ; 80: 170-179, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34656722

RESUMO

BACKGROUND: Beta-blockers have become the cornerstone for medical management in patients with chronic type B aortic dissection (TBAD). However, the effect of being on and/or receiving intravenous beta-blockers during hospitalization on outcomes of surgical repair of TBAD is not fully described. We sought to investigate this association during open surgical repair (OSR) and endovascular (Endo) intervention for nontraumatic TBAD. METHODS: The Premier Healthcare Database was inquired (June/2009-March/2015). Patients with nontraumatic isolated TBAD were identified via ICD-9-CM diagnosis and procedural codes. Patients with codes that indicated TAAD were excluded. In-hospital mortality, cardiac complications (CHF, MI, arrythmia) and stroke were evaluated. Log binomial regression analyses with bootstrapping were performed to assess the relative risk of adverse outcomes. RESULTS: A total of 1,752 were admitted for OSR (54.3%) and Endo (45.7%) TBAD repair. Use of oral beta blocker (BB) was 16.0% in OSR and 56.4% in Endo groups. In each arm, patients on BB were more likely to be diabetic, on aspirin or statin and more likely to receive additional IV BB than nonBB patients. There was no significant difference in age, sex, race, or prior history of CHF between BB and nonBB groups. Mortality was proportionally lower in patients on BB in OSR group (7.9% vs. 16.7%; P = 0.006) and Endo (3.3% vs. 9.2%; P < 0.001). The adjusted relative risk for mortality and stroke were significantly lower in oral BB recipients compared with none [aRR (95% CI): 0.53 (0.32-0.90) and 0.46 (0.25-0.87); both P ≤ 0.02]. IV metoprolol was the only IV BB that reduced mortality [aRR (95% CI): 0.62 (0.46-0.85); P = 0.003]. A dose of ≤10 mg was associated with significant mortality reduction: 6.3% (3.0-9.5%) compared with 8.1% (4.6-11.6%) in no IV BB group. Cardiac complications were not affected by BB use. CONCLUSIONS: For patients with nontraumatic TBAD, use of oral BB was associated with significant protection against in-hospital mortality and stroke following repair. Metoprolol was the only Intravenous BB type associated with improved survival. Further research is warranted to elucidate the effect of beta-blockers on the long-term surgical outcomes of TBAD.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Aneurisma Dissecante/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Metoprolol/administração & dosagem , Administração Oral , Bases de Dados Factuais , Procedimentos Endovasculares , Feminino , Mortalidade Hospitalar , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/prevenção & controle , Taxa de Sobrevida
14.
Am J Emerg Med ; 51: 248-256, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34781150

RESUMO

BACKGROUND: Intravenous diltiazem and metoprolol are both commonly used to treat atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED), but the advantages and disadvantages of these drugs cannot be verified. This meta-analysis aimed to assess the efficacy and safety of intravenous diltiazem versus metoprolol for AF with RVR. METHOD: We systematically searched PubMed, Web of Science, Embase, Cochrane library, the China National Knowledge Infrastructure (CNKI), Wanfang, China Biology Medicine disc (CBM) and the WeiPu (VIP). Meta-analysis was performed using weighted mean difference (WMD), relative risk (RR) and 95% confidence interval (CI). Statistical analysis was performed using Review Manager 5.4.1. RESULTS: Seventeen studies involving 1214 patients in nine randomized controlled trials (RCTs) and eight cohort studies were included in meta-analysis, including 643 patients in the intravenous diltiazem group and 571 patients group in the intravenous metoprolol. The results of the meta-analysis showed that compared with intravenous metoprolol, intravenous diltiazem was found higher efficacy (RR =1.11; 95% CI = 1.06 to 1.16, p < 0.00001), shorter average onset time (RR = -1.13; 95% CI = -1.97 to -0.28, p = 0.009), lower ventricular rate (RR = -9.48; 95% CI = -12.13 to -6.82, p<0.00001), less impact on systolic blood pressure (WMD = 3.76; 95% CI: 0.20 to 7.33, P = 0.04), and no significant difference in adverse events (RR = 0.80, 95% CI = 0.55 to 1.14, P = 0.22) and diastolic blood pressure (WMD = -1.20; 95% CI: -3.43 to 1.04, P = 0.29) was found between intravenous diltiazem and metoprolol. CONCLUSION: Intravenous diltiazem has higher efficacy, shorter average onset time, lower ventricular rate, less impact on blood pressure, and with no increase in adverse events compared to intravenous metoprolol.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Diltiazem/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Metoprolol/uso terapêutico , Administração Intravenosa , Pressão Sanguínea/efeitos dos fármacos , Diltiazem/administração & dosagem , Humanos , Metoprolol/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Cardiovasc Toxicol ; 22(2): 99-107, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34800264

RESUMO

Cardiomyocyte senescence is involved in the pathological mechanism of cardiac diseases. Metoprolol is a ß1 receptor blocker used for the treatment of hypertension. Recent studies show that Metoprolol can protect cardiomyocytes against ischemia injury. The present study aims to investigate the protective effects of Metoprolol against arginine vasopressin (AVP)-induced cellular senescence in cultured cardiomyocytes. The cell proliferation assay and cytotoxicity lactate dehydrogenase assay showed that the highest tolerated dosage of Metoprolol in H9C2 cardiomyocytes was optimized as 10 µM. The enzyme-linked immunosorbent assay showed that Metoprolol significantly ameliorated the elevated level of the DNA oxidation product 8-hydroxy-2 deoxyguanosine. Metoprolol also decreased the percentage of senescence-associated ß-galactosidase positive cells and improved the telomerase activity under AVP exposure. Moreover, treatment with Metoprolol ameliorated the decreased intracellular nicotinamide phosphoribosyltransferase activity, nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD+/NADPH) ratio, and Sirtuin1 activity in cardiomyocytes by AVP. Finally, Metoprolol was able to downregulate the AVP-induced expression of acetylated p53 and p21. Taken together, our data reveal that Metoprolol protected the cardiomyocytes from AVP-induced senescence.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Arginina Vasopressina/toxicidade , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Metoprolol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Acetilação , Animais , Linhagem Celular , Citocinas/metabolismo , Dano ao DNA/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , NAD/metabolismo , NADP/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Processamento de Proteína Pós-Traducional , Ratos , Transdução de Sinais , Telomerase/metabolismo
16.
Clin Res Cardiol ; 111(2): 141-153, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32572551

RESUMO

BACKGROUND: Cardiac graft denervation causes inadequate sinus tachycardia in patients after heart transplantation (HTX) which is associated with reduced survival. This study investigated the 5-year results of heart rate control with ivabradine or metoprolol succinate in patients after HTX. METHODS: This registry study analyzed 104 patients receiving either ivabradine (n = 50) or metoprolol succinate (n = 54) within 5 years after HTX. Analysis included patient characteristics, medication, echocardiographic features, cardiac catheterization data, cardiac biomarkers, heart rates, and post-transplant survival including causes of death. RESULTS: Demographics and post-transplant medication revealed no significant differences except for ivabradine and metoprolol succinate use. At 5-year follow-up, patients with ivabradine had a significantly lower heart rate (73.3 bpm) compared to baseline (88.6 bpm; P < 0.01) and to metoprolol succinate (80.4 bpm; P < 0.01), a reduced left ventricular mass (154.8 g) compared to baseline (179.5 g; P < 0.01) and to metoprolol succinate (177.3 g; P < 0.01), a lower left ventricular end-diastolic pressure (LVEDP; 12.0 mmHg) compared to baseline (15.5 mmHg; P < 0.01) and to metoprolol succinate (17.1 mmHg; P < 0.01), and a reduced NT-proBNP level (525.4 pg/ml) compared to baseline (3826.3 pg/ml; P < 0.01) and to metoprolol succinate (1038.9 pg/ml; P < 0.01). Five-year post-transplant survival was significantly better in patients with ivabradine (90.0%) versus metoprolol succinate (68.5%; P < 0.01). CONCLUSION: Patients receiving ivabradine showed a superior heart rate reduction and a better left ventricular diastolic function along with an improved 5-year survival after HTX.


Assuntos
Antiarrítmicos/uso terapêutico , Transplante de Coração/efeitos adversos , Ivabradina/uso terapêutico , Metoprolol/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Taquicardia Sinusal/tratamento farmacológico , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Sistema de Registros , Taquicardia Sinusal/etiologia , Resultado do Tratamento
17.
J Clin Pharmacol ; 62(1): 76-86, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34383318

RESUMO

Tramadol is an opioid medication used to treat moderately severe pain. Cytochrome P450 (CYP) 2D6 inhibition could be important for tramadol, as it decreases the formation of its pharmacologically active metabolite, O-desmethyltramadol, potentially resulting in increased opioid use and misuse. The objective of this study was to evaluate the impact of allosteric and competitive CYP2D6 inhibition on tramadol and O-desmethyltramadol pharmacokinetics using quinidine and metoprolol as prototypical perpetrator drugs. A physiologically based pharmacokinetic model for tramadol and O-desmethyltramadol was developed and verified in PK-Sim version 8 and linked to respective models of quinidine and metoprolol to evaluate the impact of allosteric and competitive CYP2D6 inhibition on tramadol and O-desmethyltramadol exposure. Our results show that there is a differentiated impact of CYP2D6 inhibitors on tramadol and O-desmethyltramadol based on their mechanisms of inhibition. Following allosteric inhibition by a single dose of quinidine, the exposure of both tramadol (51% increase) and O-desmethyltramadol (52% decrease) was predicted to be significantly altered after concomitant administration of a single dose of tramadol. Following multiple-dose administration of tramadol and a single-dose or multiple-dose administration of quinidine, the inhibitory effect of quinidine was predicted to be long (≈42 hours) and to alter exposure of tramadol and O-desmethyltramadol by up to 60%, suggesting that coadministration of quinidine and tramadol should be avoided clinically. In comparison, there is no predicted significant impact of metoprolol on tramadol and O-desmethyltramadol exposure. In fact, tramadol is predicted to act as a CYP2D6 perpetrator and increase metoprolol exposure, which may necessitate the need for dose separation.


Assuntos
Analgésicos Opioides/farmacocinética , Inibidores do Citocromo P-450 CYP2D6/farmacologia , Citocromo P-450 CYP2D6/efeitos dos fármacos , Tramadol/análogos & derivados , Tramadol/farmacocinética , Área Sob a Curva , Inibidores do Citocromo P-450 CYP2D6/farmacocinética , Interações Medicamentosas , Meia-Vida , Humanos , Taxa de Depuração Metabólica , Metoprolol/farmacologia , Modelos Biológicos , Quinidina/farmacologia
19.
Can Assoc Radiol J ; 73(1): 240-248, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34293933

RESUMO

BACKGROUND: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost. MATERIALS AND METHODS: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality. RESULTS: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status. CONCLUSION: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Hemodinâmica/efeitos dos fármacos , Metoprolol/administração & dosagem , Propanolaminas/administração & dosagem , Administração Intravenosa , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/economia , Angiografia por Tomografia Computadorizada/economia , Angiografia Coronária/economia , Análise Custo-Benefício/economia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Metoprolol/economia , Pessoa de Meia-Idade , Propanolaminas/economia , Estudos Prospectivos , Método Simples-Cego
20.
J Vet Pharmacol Ther ; 45(2): 177-187, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34913168

RESUMO

Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04 mg/kg) and PO (6 mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72 h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics were modeled using a 3-compartment model and non-linear least squares regression. Median (range) MET concentration was 110 (40.1-197) ng/ml collected 1 min (0.0167 h) after a bolus IV administration. Maximum concentration (Cmax ) after PO administration was 2135 (1590-4170) ng/ml at 0.5 (0.25-0.5) hours. Oral bioavailability was 54% (17-100%). Median apparent volume of distribution was 0.39 (0.17-0.58) l/kg, clearance was 12.63 (11.41-18.94) ml/kg/min, and elimination half-life was 21.1 (7.46-34.36) minutes. No clinically relevant effects of IV or PO metoprolol were noted on cardiac rhythm or NIBP. Sweating was the most common side effect. The metoprolol doses used in this study achieve plasma concentrations reported to achieve ß-blockade in humans.


Assuntos
Metoprolol , Espectrometria de Massas em Tandem , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida/veterinária , Estudos Cross-Over , Meia-Vida , Cavalos , Injeções Intravenosas/veterinária , Metoprolol/farmacocinética , Metoprolol/farmacologia , Espectrometria de Massas em Tandem/veterinária
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