Efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure and its effect on N-terminal pro-brain natriuretic peptide level / 中国基层医药

Objective:To investigate the clinical efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure and its effect on N-terminal pro-brain natriuretic peptide (NT-pro BNP) level.Methods:The clinical data of 89 patients with chronic heart failure who received treatment in Jinan 2 nd People's Hospital from January 2020 to April 2022 were retrospectively analyzed. These patients were divided into Group A ( n = 48) and Group B ( n = 41) according to different treatment methods. Group A was treated with sacubitril and valsartan combined with bisoprolol. Group B was treated with sacubitril and valsartan combined with metoprolol. All patients were treated for 3 months. Clinical efficacy as well as heart function and NT-pro BNP level pre- and post-treatment were compared between the two groups. The incidence of adverse reactions was calculated in each group. Results:Total response rate in group A was significantly higher than that in group B [95.83% (46/48) vs. 82.93% (34/41), χ2 = 4.05, P < 0.05]. After treatment, the left ventricular ejection fraction in both groups increased significantly and the left ventricular ejection fraction in group A was significantly higher than that in group B ( t = 2.19, P < 0.05). After treatment, NT-pro BNP level in group A was (416.51 ± 30.56) ng/L, which was significantly lower than (450.20 ± 35.79) ng/L in group B ( t = 4.79, P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:The efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure is superior to that of sacubitril and valsartan combined with metoprolol. The former can greatly decrease NT-pro BNP level. Corresponding drugs can be selected for the treatment of chronic heart failure according to the actual needs of patients.

Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process / 药学学报

With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.

Protective Effect of Combined Metoprolol and Atractylenolide I in Rats with Acute Myocardial Infarction via Modulation of the SIRT3/ß-CATENIN/PPAR-γ Signaling Pathway

ABSTRACT Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/ß-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, ß-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, ß-catenin, and PPAR-γ

Comparison of diltiazem and metoprolol for atrial fibrillation with rapid ventricular rate: Systematic review and meta-analysis

Background: Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid ventricular rate (AFRVR) in the emergency department. Objectives: To compare the efficacy of intravenous diltiazem and metoprolol for rate control and safety with respect to development of hypotension and bradycardia in patients with AF-RVR. Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane databases, and the clinicaltrials.gov registry between database inception and 30th May 2021. Articles were included if they compared efficacy and safety of diltiazem versus metoprolol in critically ill adult patients hospitalized with AF-RVR. Outcome measures were achievement of rate control, development of new hypotension, and bradycardia after drug administration. Results: Of 86 records identified, 14 were eligible, all of which had a low to moderate risk of overall bias. The meta-analysis (Mantel-Haenszel, random-effects model) showed that diltiazem use was associated with increased achievement of rate control target compared to metoprolol [14 studies, n ¼ 1732, Odds Ratio (OR): 1.92; 95% Confidence Intervals (CI):1.26 to 2.90; I2 ¼ 61%]. In the pooled analysis, no differences were seen in hypotension using diltiazem vs metoprolol [12 studies, n ¼ 1477, OR: 0.96; 95% CI:0.61 to 1.52; I2 ¼ 35%] or bradycardia [9 studies, n ¼ 1203, OR: 2.44; 95% CI: 0.82 to 7.31; I2 ¼ 48%]. Conclusions: Intravenous diltiazem is associated with increased achievement of rate control target in patients with AF-RVR compared to metoprolol, while both medications are associated with similar incidence of hypotension and bradycardia.

Effect of Fixed-Dose Combination of Efonidipine + S(-) Metoprolol in Indian Hypertensive Patients

Aim: To evaluate the antihypertensive efficacy and safety of the fixed-dose combination (FDC) of Efonidipine and S (-) Metoprolol in adult patients with hypertension. Study Design: Multicentric, double-blind, randomized, parallel, comparative Phase III trial. Methodology: This clinical trial was conducted at five geographically distributed sites across India and enrolled 240 hypertensive patients. They were randomized (1:1) to receive either FDC of Efonidipine 40 mg + S (-) Metoprolol 25 mg tablet (E+S(-)M group) or FDC of Cilnidipine 10 mg + Metoprolol 50 mg tablet (C+M group) once daily for 90 days. Patients were evaluated for changes in their blood pressure (BP) from baseline to Day 30, 60 and 90. The study site staff, investigator and patients were blinded to the treatment allocation. Blood pressure was recorded as the mean of 3 consecutive measurements taken in a sitting position. Patients achieving target BP (<140/90 mmHg) were evaluated and the safety and tolerability were assessed based on the incidences of adverse events (AEs). Results: This study focused on evaluating the mean Systolic BP (SBP) and Diastolic BP (DBP) reduction from baseline to Day 30, 60 and 90. At baseline, patients had a mean (±SD) SBP and DBP of 154.60 (±11.33) mmHg and 98.68 (±8.18) mmHg respectively. After 30 days of the E+S(-)M treatment, the mean SBP/DBP was 136.06±10.55/ 86.68±5.51 mmHg (p<0.0001) and on Day 60 it was 129.48±10.51/ 84.17±5.51mmHg (P <0.0001), corresponding to mean reductions in SBP/DBP of 18.09/11.66 and 24.78/14.17 mmHg, respectively. There was a statistically significant (p <0.0001) reduction to 123.59 ± 15.21 mmHg in SBP and 82.38 ± 5.05 mmHg in DBP observed on Day 90 as compared to baseline. Post-treatment with E+S(-)M group, SBP/DBP reduction of 31.01/16.29 mmHg in hypertensive patients was observed. A total of 95% of the patients achieved a pre-defined target BP <140/90 mmHg on the administration of E+S(-)M. Furthermore, it was observed that 93% of Stage I and 96% of Stage II hypertensive patients achieved the target BP goal. A total of 5.78% of patients experienced adverse events (AEs) in the E+S(-)M group which was similar to that of C+M group. All AEs were mild in severity and resolved without any sequelae at the end of the study. No unexpected adverse events were reported, and the E+S(-)M dosage regimen was well tolerated by the patients. Both the treatment groups were non-inferior to each other. Conclusion: The study results demonstrated clinically meaningful reductions in blood pressure after administration of FDC of Efonidipine 40 mg + S(-) Metoprolol 25 mg over a period of 90 days. The treatment was efficacious, safe, and well?tolerated in the study population.

Short-Term Results of Ivabradine versus Metoprolol: The Effects on Atrial Fibrillation in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

ABSTRACT Introduction: Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. Methods: 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. Results: There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups.

Nationwide surveillance for S-Metoprololtreatment effect on blood pressure control against sympathetic overdrive in Indian patients with hypertension (PROTECT)

Background:Patients with hypertension in India been reported with high heart rate owing to sympathetic overdrive (SO). Beta-blockers provides several positive effects to reduce SO in patients with hypertension. The aim of present survey studywasto understand current real-world prevalence of SO in Indian patients with hypertension and usage of beta-blocker therapy in them.Methods:A cross sectional, observational, questionnaire-based survey conducted across India between June 2020 to October 2020. A specially designed validated questionnaire was shared with 157 registered health care practitioners (HCP),their anonymous inputs were captured and analysed in qualitative manner. Categorical data was summarized by number (n) and percentage (%). Results:Total 157 HCP participated and completed the survey. Around 53% of HCP observed that patients with average heart rate above 75 beats/min were associated with negative prognosis. Around 43% of HCP reported that raised heart rate is associated with advancedage and increased body mass index (BMI). Two-third of HCP reported that tachycardia is associated with stage-2 hypertension and marked by restlessness and anxiety which is suggestive of SO. Over 70% HCP agreed that the HR below 75 beats/min is associated with good prognosis. Around 89% HCP reported beta-blockers as the drug of choice in patients with augmented SO. S-Metoprololwas reported to bethemost preferred beta-blocker agent and was recommended by 76% HCP in patients with hypertension and coexisting SO.Conclusions:SO been reported prevalent conditionin Indian patients with hypertension which likely worsensthe prognosis in these patients. Beta-blockers reported to be the preferred choice of anti-hypertensive and S-Metoprololseem to be themost preferred agent amongst the available beta-blockers against SO in patients with hypertension in India.

Quality control and drug-drug interactions between commercially available Metoprolol and Glimepiride tablets

Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.

Effects of pre-treatment with metoprolol and diltiazem on cerebral ischemia/reperfusion-induced injuries

Abstract Stroke is one of the most important health concerns worldwide. Calcium ions accumulation in the nerve cells and increase in the catecholamines level of the brain following cerebral ischemia/reperfusion (I/R) are accompanied by damaging effects. Therefore, the present study aimed to evaluate the effects of diltiazem, as a calcium channel blocker, and metoprolol, as a β-adrenoceptors antagonist, on I/R injury. In this study, 30 male Wistar rats were divided into control, I/R, metoprolol, diltiazem, and metoprolol plus diltiazem groups (n=6 in each). Metoprolol (1 mg/kg/day) and diltiazem (5 mg/kg/day) were injected intraperitoneally (i.p.) for 7 days before I/R induction. On day 8, the animals underwent ischemia by bilateral common carotid arteries occlusion for 20 min. Histopathological analysis showed a significant reduction in leukocyte infiltration in diltiazem, metoprolol, and diltiazem plus metoprolol treated rats compared with the I/R group (P<0.05, P<0.01, P<0.01, respectively). In addition, in all treated groups, myeloperoxidase activity and malondialdehyde levels in the brain tissue significantly declined compared with the I/R group (P<0.001). Furthermore, pre-treatment with diltiazem and metoprolol alone or in co-administration remarkably reduced infarct size following I/R (P<0.001). Overall, the results indicate the considerable neuroprotective effects of metoprolol and diltiazem in cerebral I/R.

Effect of Xueshuan Xinmaining tablet combined with metoprolol on cardiac enzymes and troponin in patients with coronary heart disease after percutaneous coronary intervention / 中国基层医药

Objective:To investigate the effects of Xueshuan Xinmaining tablet combined with metoprolol on creatine kinase-MB and troponin in patients with coronary heart disease after percutaneous coronary intervention. Methods:A total of 104 patients with coronary heart disease who received percutaneous coronary intervention in Zhoushan Hospital from March 2020 to March 2021 were included in this study. They were randomly divided into observation and control groups ( n = 52/group). The control group was give metoprolol (oral, 25 mg once,3 times/day). The observation group was given Xueshuan Xinmaining tablet (2 tablets once, 3 times per day) based on medication given in the control group. Two groups were treated for 1 month. Clinical efficacy, changes in vascular endothelial function and serum inflammatory factors post-treatment relative to those before treatment, and the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [86.54% (45/52) vs. 67.31% (35/52), χ2 = 4.99, P < 0.05]. After treatment, nitric oxide in the observation group was significantly higher than that in the control group [(67.23 ± 9.52) μmol/L vs. (60.49 ± 9.71) μmol/L, t = 3.57, P < 0.001]. Endothelin in the observation group was significantly lower than that in the control group [(53.12 ± 7.28) ng/L vs. (61.25 ± 8.36) ng/L, t = 5.28, P < 0.001]. Tumor necrosis factor α, C-reactive protein and interleukin-6 in the observation group were (39.51 ± 6.37) μg/L, (4.13 ± 1.02) mg/L, and (19.43 ± 2.57) μg/L, respectively, which were significantly lower than (51.37 ± 7.28) μg/L, (5.62 ± 1.15) mg/L, (26.16 ± 3.19) μg/L in the control group ( t = 8.84, 6.99, 11.84, all P < 0.05). Creatine kinase-MB and troponin in the observation group were (30.18 ± 5.89) U/L and (7.32 ± 1.12) ng/L, respectively, which were significantly lower than (41.74 ± 6.76) U/L and (9.63 ± 1.45) ng/L in the control group, respectively ( t = 9.29, 9.09, both P < 0.05). No serious adverse reactions occurred during the treatment period in each group. Conclusion:Xueshuan Xinmaining tablet combined with metoprolol exhibit remarkable therapeutic effects on patients with coronary heart disease subjected to percutaneous coronary intervention. The combined therapy can greatly reduce inflammatory reaction and decrease creatine kinase-MB level and improve vascular endothelial function.

Segurança, Eficácia e Protocolo de Dose de Metoprolol para Redução de Frequência Cardíaca em Pacientes Pediátricos Externos que Passaram por Angiografia Cardíaca por TC / Safety, Efficacy, and Dose Protocol of Metoprolol for Heart Rate Reduction in Pediatric Outpatients Undergoing Cardiac CT Angiography

Resumo Fundamento Qualidade de imagem e dose de radiação são otimizadas com uma frequência cardíaca (FC) lenta e estável na realização de imagens de artérias coronárias durante a angiografia cardíaca por tomografia computadorizada (CCTA, do inglês cardiac computed tomography angiography) A segurança, a eficácia e o protocolo para a redução da FC com medicamento betabloqueador ainda não foi bem descrita em uma população de pacientes pediátricos. Objetivo Oferecer um protocolo de dose de metoprolol eficiente a ser usado em pacientes pediátricos externos durante a CCTA. Métodos Realizamos uma revisão retrospectiva de todos os pacientes pediátricos externos que receberam o metoprolol durante a CCTA. As características demográficas e clínicas foram resumidas e a redução média em FC foi estimada utilizando-se um modelo de regressão linear multivariada. As imagens foram avaliadas em uma escala de 1 a 4 (1= ideal). Resultados Um total de 78 pacientes externos passaram a uma CCTA com o uso de metoprolol. A média de idade foi de 13 anos, a média de peso foi de 46 kg, e 36 pacientes (46%) eram do sexo masculino. As doses médias de metoprolol foram 1,5 (IQR 1,1; 1,8) mg/kg, e 0,4 (IQR 0,2; 0,7) mg/kg para administrações orais e intravenosas, respectivamente. O produto dose-comprimento por exame foi de 57 (IQR 30, 119) mGy*cm. A redução média da FC foi 19 (IQR 12, 26) batimentos por minuto, ou 23%. Não foram relatadas complicações ou eventos adversos. Conclusão O uso de metoprolol num cenário de pacientes pediátricos externos para redução da FC antes de uma CCTA é seguro e eficiente. Pode-se reproduzir um protocolo de dose de metoprolol quando for necessário atingir uma FC mais lenta, garantindo tempos de aquisição mais rápidos, imagens mais claras e redução na exposição à radiação nessa população. (Arq Bras Cardiol. 2021; 116(1):100-105)

Abstract Background Image quality and radiation dose are optimized with a slow, steady heart rate (HR) when imaging the coronary arteries during cardiac computed tomography angiography (CCTA). The safety, efficacy, and protocol for HR reduction with beta blocker medication is not well described in a pediatric patient population. Objective Provide a safe and efficient metoprolol dose protocol to be used in pediatric outpatients undergoing CCTA. Methods We conducted a retrospective review of all pediatric outpatients who received metoprolol during CCTA. Demographic and clinical characteristics were summarized and the average reduction in HR was estimated using a multivariate linear regression model. Images were evaluated on a 1-4 scale (1= optimal). Results Seventy-eight pediatric outpatients underwent a CCTA scan with the use of metoprolol. The median age was 13 years, median weight of 46 kg, and 36 (46%) were male. The median doses of metoprolol were 1.5 (IQR 1.1, 1.8) mg/kg and 0.4 (IQR 0.2, 0.7) mg/kg for oral and intravenous administrations, respectively. Procedural dose-length product was 57 (IQR 30, 119) mGy*cm. The average reduction in HR was 19 (IQR 12, 26) beats per minute, or 23%. No complications or adverse events were reported. Conclusion Use of metoprolol in a pediatric outpatient setting for HR reduction prior to CCTA is safe and effective. A metoprolol dose protocol can be reproduced when a slower HR is needed, ensuring faster acquisition times, clear images, and associated reduction in radiation exposure in this population. (Arq Bras Cardiol. 2021; 116(1):100-105)

A New Validated Third Order Derivative Spectroscopic Method For Simultaneous Estimation Of Metoprolol Succinate And Ramipril In Tablet Dosage Form

Objective: The objective of the present work is to develop and validate a new UV derivative spectrophotometric method for simultaneous estimation of metoprolol succinate and ramipril in methanol: water (50:50v/v). Methods: “Zero crossing technique” was chosen for quantitative determination. The zero-crossing points (ZCP’s) were found to be 209 nm where metoprolol succinate was quantified and 211 nm where ramipril was quantified. This method was then subjected to accuracy, linearity, sensitivity and reproducibility according to ICH guidelines to ensure and confirm its validity. Results: The method was found to be obeying Beer’s law in the range of 10-50 µg/ml and 5-25 µg/ml for metoprolol succinate and ramipril, respectively. The % recoveries were observed between the range of 99.2-100.2 for metoprolol succinate and 99.57-99.86 for ramipril. The intra-day and inter-day results showed reproducibility. Conclusion: It can be concluded that the developed third-order UV derivative spectroscopic method for the simultaneous determination of metoprolol succinate and ramiprilcan be recommended for routine quantitative analysis.

Preparation and Drug Release Mechanism of Time Controlled Explosive Pulsatile Tablets with Ethylcellulose Coating

Background The time rhythm of human body is associated with the occurrence and development of manydiseases, and it also affects the efficacy and pharmacokinetic characteristics of the corresponding therapeuticdrugs. Therefore, the chronopharmacological drug delivery system has potential applications. Aim In this work, it is proposed to develop a kind of pulsatile release tablet of simple structure and preparingprocess, thus to provide an alternative drug delivery system for therapeutic agents used in treatment of diseasesof typical onset biorhythm at period inconvenient to take drug.Methods Metoprolol tartrate (MT), a drug widely used clinically to treat cardiovascular diseases was selected asa model drug for developing pulsatile tablets of time-controlled explosive system (TES). The MT pulsatile tabletswere ethyl cellulose (EC) coating tablets produced by pan coating process, and the core tablets were preparedby direct compression. The formulation and process was optimized by single factor test and orthogonal design.Also, the pulsatile release mechanism of the tablets was discussed through investigating the water absorptionand swelling capacity of tablets as well as the mechanical properties of EC free film.Results A kind of pulsatile tablets of MT were developed with a drug release lag time around 7 h and a fastrelease of drug after lag time. When the swelling force of core tablet caused by water uptake was high enoughover the tensile strength of EC coating film, the MT pulsatile tablets demonstrated a shell-type exploding rupturedue to the great rigidity and weak flexibility of EC film, and then a fast pulsatile release of drug was observed.Both the swelling capacity of core tablet and the thickness of coating film together controlled the lag time of drugrelease. The lag time showed a good linear relationship with the thickness of coating film (r = 0.9984, P < 0.01).The sort and amount of fillers and disintegrants dominated the release behaviour after lag time.Conclusion The developed MT pulsatile tablets can exert a timely release of drug before peak onset period ofhypertension and angina pectoris early in the morning after drug taking around 22:00 P.M the night before. Thegood linear relationship between lag time and coating thickness enabled the pulsatile tablets to be used fordelivery of other therapeutic agents of similar chronotherapy demand by adjusting the coating thickness toachieve the appropriate lag time of drug release to match the different high attack rhythm of the exact diseases.

Drug Release and Pharmacokinetics Behavior of a Simple Ethylcellulose Coating Pulsatile Tablet of Time-controlled Explosive System

Background The time rhythm of human body is associated with the occurrence and development of manydiseases. Kinds of diseases of particular onset biorhythm provided the room for the development ofchronopharmacological drug delivery systems.Aim In this work, the drug release and pharmacokinetics behavior of metoprolol tartrate (MT) pulsatile tabletdeveloped in our lab was investigated to figure out its feasibility of convenient drug taking to exert effectivechronotherapy for cardiovascular diseases like hypertension and angina pectoris.Methods The in vitro release behavior of MT pulsatile tablets was investigated by using basket method. Theappearance and morphology of MT pulsatile tablets during drug release was observed by naked eye and scanning electronic microscope, respectively. In vivo pharmacokinetics performance was studied in NewZealand rabbits.Results The lag time of MT pulsatile tablets was approximately 7 h in vitro, and a fast release was observedthereafter, with more than 90% releasing within 10 min. The pharmacokinetics study in rabbits demonstrateda perfect consistence in the absorption lag time of 7.04 ± 0.29 h in vivo. Compared with the marketedconventional tablet, the MT pulsatile tablet showed a bioequivalence in absorption extent with a relativebioavailability of 110.04%, but not in absorption rate.Conclusion The designed lag time of 7 hours enabled the MT pulsatile tablets to achieve effectivechronotherapy for cardiovascular diseases like hypertension and angina pectoris with a high attack rhythmaround 4:00-6:00 A.M by giving medicine conveniently around 22:00 P.M. the night before.

A comparative study on efficacy of metoprolol and ivabradine in acute ST elevation myocardial infarction patients

Background: The ST-elevation myocardial infarction (STEMI), a fatal disease, is rapidly extending in patients, worldwide. Therefore, proper and timely diagnosis followed by appropriate management becomes necessary. The study aimed to compare the effectiveness of metoprolol and ivabradine in acute STEMI patients.Methods: This was an observational, comparative, in-hospital study carried out in patients admitted in the in-patient cardiac department, intensive cardiac care unit of a tertiary care centre in India. Total 60 patients diagnosed with acute ST-elevation MI were included in the study and were equally divided into two groups. Group 1 involved patients who were given metoprolol for treatment and group 2 involved patients who were given ivabradine. The patients were assessed in terms of heart rate, NYHA class, and ejection fraction. Follow-up of 30 days was taken in all patients.Results: Ivabradine reduced mean heart rate from 85.57 bpm at baseline to 78.23 bpm. Heart rate in the metoprolol group was reduced from 81.93 bpm to 76.47 bpm over the same time period. Metoprolol and ivabradine showed significant improvement in the ejection fraction volume during the in-hospitalization stay. Ivabradine showed a better improvement in ejection fraction when compared to metoprolol but the difference was not found to be statistically significant. Higher mortality was assessed in ivabradine group compared to metoprolol.Conclusions: The study gives the gold standard efficacy and mortality benefit of metoprolol, although ivabradine on the other hand gave better responses in heart rate reduction and improvements in ejection fraction.

Comparison of Oral Ivabradine, Oral Metoprolol and Placebo to Attenuate the Stress Response in Nasal and Laryngeal Surgeries: A Prospective, Randomized, Double Blind Study

Introduction: Nasal surgeries like septoplasty, polypectomyand laryngeal surgeries for removal of vocal nodule, cysts etcare commonly performed. Changes in haemodynamics due tolaryngoscopy and endotracheal intubation are likely to persistduring these procedures. These surgeries also require bloodless field. The present study was conducted to evaluate andcompare the efficacy of oral metoprolol tartrate versus oralivabradine versus placebo in attenuation of haemodynamicresponses during laryngoscopy, tracheal intubation andthroughout nasal and laryngeal surgeries.Methods: This was a prospective, randomized, comparative,double blind study. . Patients were randomly allocated bysimple randomization into 3 groups having 30 patients in each.Neither the patient nor the investigator was aware, whichpatient is allocated into which group and were unaware of thedrug being administered as it was given to the patient by aperson not involved in the study. Data collections were carriedout by investigator in a double blind manner. All the patientswere explained about the anesthesia technique and writteninformed consent was taken. Group 1: Oral Ivabradine 5mgtablet was given orally 2 hours before induction of anaesthesia.Group 2: Oral Metoprolol tartrate 50mg tablet was given orally2 hours before induction of anaesthesia. Group 3: Oral placebowas given 2 hours before induction of anaesthesia.Results and Conclusion: We concluded that both the drugscan be used as an effective premedication, to attenuate thesympathetic response to laryngoscopy, endotrachealintubation, extubation and throughout nasal and laryngealsurgeries. However Metopolol was found to have better controlthan Ivabradine in maintaining the vitals at all points andproviding a good hypotensive effect than ivabradine.

Effects of CYP2D610 on plasma trough concentration of metoprolol in patients with coronary artery disease / 南方医科大学学报

OBJECTIVE@#To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease.@*METHODS@#The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes.@*RESULTS@#In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them.@*CONCLUSIONS@#CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.

Metoprolol treatment of dual cocaine and bupropion cardiovascular and central nervous system toxicity

Cardiovascular and central nervous system (CNS) toxicity, including tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion use. We report acute toxicity from the concomitant use of cocaine and bupropion in a 25-year-old female. She arrived agitated and uncooperative, with a history of possible antecedent cocaine use. Her electrocardiogram demonstrated tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses of 5 mg intravenous metoprolol were administered, which resolved the agitation, tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive toxicology screen returned positive for both cocaine and bupropion. We believe clinicians should be aware of the potential for synergistic cardiovascular and CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent an effective initial treatment. Unlike benzodiazepines, metoprolol directly counters the pharmacologic effects of stimulants without respiratory depression, sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has good penetration of the CNS and can counter stimulant-induced agitation.

Therapeutic effect of metoprolol tartrate on UAP and its influence on levels of blood lipids and inflam‐ matory factors／ / 心血管康复医学杂志

Objective :To observe therapeutic effect of metoprolol tartrate on unstable angina pectoris (UAP) and its influence on levels of blood lipids and inflammatory factors .Methods :A total of 96 UAP patients treated in our hos‐pital from Jan 2016 to Jun 2017 were randomly and equally divided into routine treatment group and metoprolol group (received metoprolol tartrate based on routine treatment ) ,both groups were continuously treated for 14d. Onset times and duration of angina pectoris ,visual analogue scale (VAS) score for pain degree ,levels of blood lip‐ids ,serum hsCRP ,TNF‐α ,MMP‐9 and plasma BNP ,and therapeutic effect were observed and compared between two groups before and after treatment .Results :Compared with routine treatment group after treatment ,there were significant reductions in onset times [ (5.67 ± 3.57) times／week vs .(2.81 ± 1. 18) times／week] and duration [ (4. 51 ± 1. 43) min／time vs.(1.37 ± 0. 87) min／time] of angina pectoris ,VAS score for pain degree [(5.69 ± 0.87) scores vs.(4. 08 ± 0.61 ) scores] ,levels of serum hsCRP [ (18.34 ± 4. 16 ) mg／L vs.(14.59 ± 3. 98 ) mg／L ] , TNF‐α [ (173. 41 ± 21.42) μg／L vs.(119. 03 ± 21. 83) μg／L] ,MMP‐9 [(368.51 ± 38. 24) μg／L vs.(303.77 ± 29. 97) μg／L] and plasma BNP [ (869.78 ± 82.89) pg／ml vs.(721. 36 ± 75.62) pg／ml] in metoprolol group , P＝0. 001 all. Conclusion :Metoprolol tartrate can improve therapeutic effect ,significantly improve angina and reduce serum levels of inflammatory factors in UAP patients .

Effect of isosorbide mononitrate combined with metoprolol in the treatment of heart failure in patients with coronary heart disease / 中国基层医药

Objective To observe the clinical effect of isosorbide mononitrate combined with metoprolol in the treatment of coronary heart failure.Methods From January 2015 to May 2017,100 patients with coronary heart failure treated in the Second People's Hospital of Yuyao were randomly divided into two groups according to the digital table,with 50 cases in each group.The conventional group was treated with conventional therapy.The observation group was treated with isosorbide mononitrate combined with metoprolol on the basis of conventional treatment for 30 days.The clinical efficacy,cardiac function index and plasma BNP level were compared between the two groups.Results The total effective rate of the observation group was 96.0％ (48/50),which was higher than 78.0％ (39/50) in the conventional group(x2 =7.161,P ＜ 0.01).After treatment,the cardiac drainage index(CI) [(3.14 ± 0.53) L · min-1 · (m2)-1],cardiac output blood volume (CO) [(5.62 ± 0.95) L/min],each stroke volume (SV) [(79.24 ± 2.56) mL],left ventricular ejection fraction (LVEF) [(61.62 ± 4.95) ％] in the observation group were better than those in the conventional group[(2.41 ±0.45) L · min-1 · (m2)-1,(4.79 ± 0.23) L/min,(72.30 ± 2.78)mL,(53.79 ±4.23)％,t =7.043,5.696,12.318,8.066,all P ＜0.05].The BNP level of the observation group was (172.17 ± 10.36) pg/mL,which was lower than (215.47 ± 12.48) pg/mL of the conventional group (t =17.908,P ＜ 0.05).Conclusion The treatment of coronary heart failure with isosorbide mononitrate and metoprolol can improve the clinical effect and improve cardiac function.