Search

Background: Atrial fibrillation (AF) and/or atrial flutter (AFL) with rapid ventricular response (RVR) is a condition that often requires urgent treatment. Although guidelines have recommendations regarding chronic rate control therapy, recommendations on the best choice for acute heart rate (HR) control in RVR are unclear. Methods: A systematic search across multiple databases was performed for studies evaluating the outcome of HR control (defined as HR less than 110 bpm and/or 20% decrease from baseline HR). Included studies evaluated AF and/or AFL with RVR in a hospital setting, with direct comparison between intravenous (IV) diltiazem and metoprolol and excluded cardiac surgery and catheter ablation patients. Hypotension (defined as systolic blood pressure less than 90 mmHg) was measured as a secondary outcome. Two authors performed full-text article review and extracted data, with a third author mediating disagreements. Random effects models utilizing inverse variance weighting were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 test. Results: A total of 563 unique titles were identified through the systematic search, of which 16 studies (7 randomized and 9 observational) were included. In our primary analysis of HR control by study type, IV diltiazem was found to be more effective than IV metoprolol for HR control in randomized trials (OR 4.75, 95% CI 2.50–9.04 with I2 = 14%); however, this was not found for observational studies (OR 1.26, 95% CI 0.89–1.80 with I2 = 55%). In an analysis of observational studies, there were no significant differences between the two drugs in odds of hypotension (OR 1.12, 95% CI 0.51–2.45 with I2 = 18%). Conclusion: While there was a trend toward improved HR control with IV diltiazem compared with IV metoprolol in randomized trials, this was not seen in observational studies, and there was no observed difference in hypotension between the two drugs. [ABSTRACT FROM AUTHOR]

A suitable RP-UPLC method for the quantitative analysis of degradation impurities of Benidipine hydrochloride & Metoprolol succinate is reported. The method was validated for specificity, linearity, range, accuracy, precision, sensitivity (LOQ and LOD), and robustness. The method shows excellent linearity with linear regression (r > 0.9950) within concentration range (0.5 to 3.0 µg/mL). LOD values were 0.14, 0.16 and, 0.15 and LOQ values were 0.42, 0.49 and 0.45 µg/mL for MET impurity-B & O and BEN impurity-2, respectively. The proposed method could be applied to routine quality control analysis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of yixinshu tablets combined with metoprolol on cardiac function, hemorheology and vascular endothelial function in patients with angina pectoris of coronary heart disease. Methods: 126 patients with angina pectoris of coronary heart disease who were admitted to Nanjing Central Hospital from July 2020 to August 2022 were included. Patients were divided into control group（n=63, treated with metoprolol） and study group（n=63, treated with yixinshu tablets on the basis of control group） by random number table method. The changes of clinical symptoms, cardiac function [left ventricular ejection fraction（LVEF), cardiac output（CO), left ventricular end diastolic diameter（LVEDD）], hemorheology [plasma viscosity, whole blood high shear viscosity, whole blood low shear viscosity] and vascular endothelial function [nitric oxide（NO), endothelin-1（ET-1）] were compared between two groups, and the incidence of adverse reactions in two groups were observed. Results: 12 weeks after treatment, the number of angina pectoris attacks decreased and the duration of angina pectoris shortened in two groups, the improvement in study group was greater than that in control group（P＜0.05). 12 weeks after treatment, CO and LVEF increased and LVEDD decreased in two groups, and the improvement in study group was greater than that in control group（P＜0.05). 12 weeks after treatment, the plasma viscosity, whole blood high shear viscosity and whole blood low shear viscosity in two groups decreased, and the improvement in study group was greater than that in control group（P＜0.05). 12 weeks after treatment, ET-1 decreased and NO increased in two groups, and the improvement in study group was greater than that in control group（P＜0.05). There was no difference in the incidence of adverse reactions between control group（4.76%）and study group（6.35%）（P＞0.05). Conclusion: Yixinshu tablets combined with metoprolol can effectively improve the hemorheology, cardiac function, and endothelial function of patients with coronary heart disease and angina pectoris. [ABSTRACT FROM AUTHOR]

Background: This observational, prospective cross-sectional study aimed to assess the safety and efficacy of metoprolol and bisoprolol in the treatment of Coronary Artery Disease (CAD) patients. Materials and Methods: The study received institutional ethics approval and was conducted at a tertiary care private teaching hospital over six months. Ninety CAD patients were included, with demographics and clinical characteristics recorded. Vital signs were measured at baseline, 48 hr, 7 days, and 1 month. Angina severity was assessed using the Canadian Cardiovascular Society Grading Scale and New York Heart Association classification. Statistical analysis compared outcomes between metoprolol and bisoprolol groups. Results: Male patients (72.22%) received metoprolol more frequently, while bisoprolol was preferred among females (28.88%). Age had minimal influence on medication choice. Metoprolol-treated patients had higher Left Ventricular Ejection Fraction (LVEF) values (50.26%) compared to bisoprolol-treated patients (45.78%). Regional Wall Motion Abnormalities (RWMA) was similar between groups. Both medications effectively reduced hypertension severity and vital parameters, with significant reductions in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) with metoprolol. The prevalence of chest pain decreased in both groups, with Class III patients achieving complete relief. Breathlessness symptoms improved overall, with some patients experiencing relief while others showed reduced symptoms. Side effects were low in both groups, but metoprolol had a slightly higher incidence. Conclusion: Metoprolol and bisoprolol demonstrated safety and efficacy in managing CAD patients. Metoprolol showed advantages in LVEF improvement and greater reduction in SBP, DBP, and HR, but it had a slightly higher side effect incidence. Both medications effectively alleviated chest pain and breathlessness symptoms. This study provides valuable insights into the clinical characteristics and outcomes associated with metoprolol and bisoprolol in CAD patients, supporting their use in managing cardiac symptoms and hypertension. [ABSTRACT FROM AUTHOR]

Chitosan succinate is distinguished by its ability to shield the loaded drug from the acidic environment, localize and keep the drug at the colon site, and release the drug over an extended time at basic pH. The current study attempts to develop polyelectrolyte liposomes (PEL), using chitosan and chitosan succinate (CSSC), as a carrier for liposomal-assisted colon target delivery of 5 fluorouracil (5FU). The central composite design was used to obtain an optimized formulation of 5FU-chitosomes. The chitosan-coated liposomes (chitosomes) were prepared by thin lipid film hydration technique. After that, the optimized formulation was coated with CSSC, which has several carboxylic (COOH) groups that produce an anionic charge that interacts with the cation NH2 in chitosan. The prepared 5FU-chitosomes formulations were evaluated for entrapment efficiency % (EE%), particle size, and in vitro drug release. The optimized 5FU-chitosomes formulation was examined for particle size, zeta potential, in vitro release, and mucoadhesive properties in comparison with the equivalent 5FU-liposomes and 5FU-PEL. The prepared 5FU-chitosomes exhibited high EE%, small particle size, low polydispersity index, and prolonged drug release. PEL significantly limited the drug release at acidic pH due to the deprotonation of carboxylate ions in CSSC, which resulted in strong repulsive forces, significant swelling, and prolonged drug release. According to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, PEL treatment significantly decreased the viability of HT-29 cells. When compared to 5FU-liposome and 5FU-chitosome, the in vivo pharmacokinetics characteristics of 5FU-PEL significantly (p < 0.05) improved. The findings show that PEL enhances 5FU permeability, which permits high drug concentrations to enter cells and inhibits the growth of colon cancer cells. Based on the current research, PEL may be used as a liposomal-assisted colon-specific delivery. [ABSTRACT FROM AUTHOR]

Copyright of Archives of the Turkish Society of Cardiology / Türk Kardiyoloji Derneği Arşivi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Contamination of water bodies by emerging pollutants such as β‐blockers has been a global concern over the past few years. This is due to the bioaccumulative character of β‐blockers in the aquatic systems, and their excessive usage might cause adverse effects on both humans and aquatic biota. A reusable and recyclable magnetic chromium‐based MIL‐101 (Fe3O4@MIL‐101(Cr)) nanocomposite was used as an adsorbent for the removal of the selected β‐blockers (acebutolol and metoprolol) from wastewater. The nanocomposite's structural, magnetic and surface properties were confirmed using various characterisation techniques. The equilibrium data indicated that the maximum adsorption capacities of Fe3O4@MIL‐101(Cr) for acebutolol and metoprolol were 30.9 mg g−1 and 28.3 mg g−1, respectively. The isotherm and kinetic experimental data best fitted Langmuir isotherm and pseudo‐second‐order kinetics models. Obtained free energies using the Dubinin‐Radushkevich model were above 8 kJ mol−1, demonstrating that the interaction mechanism between β‐blockers and the Fe3O4@MIL‐101(Cr) nanocomposite was chemisorption. The prepared nanocomposite was then used to remove β‐blockers from real samples, and maximum removal efficiencies (94.1–97.1 %) were obtained in the presence of co‐existing species. The Fe3O4@MIL‐101(Cr) hybrid showed great potential for efficient and facile removal of β‐blockers from river water, effluent and influent wastewater samples. [ABSTRACT FROM AUTHOR]

Backgrounds: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. Aims and methods: We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. Results: A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. Conclusion: Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation. [ABSTRACT FROM AUTHOR]

Background: High-alert medications (HAMs) potentiate heightened risk of causing patient harm ranging from 0.24 to 89.6 errors per 100 prescriptions. High-alert medications are crucially utilized in the intensive care settings (ICUs) due to their excellent potential in delivering therapeutic efficacy, yet these medications could cause severe harm if used inappropriately. Despite the cautious use of these medications, medication safety issues persist, which compromises patient safety. Methods: A prospective interventional study was conducted in ICUs for a period of 6 months. The HAMs were adopted from the Institute for Safe Medication Practices (ISMP) list of HAMs that were used. A suitably designed medication error assessment form was used to capture the necessary data, including demographics, medications, medication error, and the contributing factors. The National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) index was used to categorize the medication errors (MEs). The error rate was calculated using error rate formula. Continuous variables were expressed as mean ± standard deviation, whereas categorical variables were presented in frequencies and percentages. Results: A total of 165 patients were enrolled during the study period, with 98 (59.4%) being male and 67 (40.6%) female. The majority [54 (32.73%)] of the study participants belonged to the 61-70 age range. A total of 204 MEs were reported, of which [92 (41.5%)] errors were prescribing errors, followed by documentation errors [69 (33.82%)] and administration errors [43 (21.08%)]. The baseline medication error rate was noted to be 160.12/1,000 patient days. Potassium chloride, tramadol, propranolol, aspirin, insulin, and metoprolol were identified as the most common HAMs to cause errors. According to NCC MERP classification, 41.18% were categorized as category B, followed by category C (35.78%). An overall of 666 contributing factors (CFs) were identified for 204 errors. Stress (24.32%) was the most common factor that contributed to the MEs, followed by workload (21.47%). Conclusion: While great strides have been adopted in error prevention, yet the goal of making HAM errors "never" event has not been achieved. Thus, an active surveillance by a clinical pharmacist could support the healthcare team in promoting patient care. [ABSTRACT FROM AUTHOR]

Background Diabetes Mellitus (DM) is a prominent health care issue worldwide. One of the most prevalent comorbidities of DM is cardiovascular disease (CVD). The objective of this study was to assess the utilization patterns of cardiovascular medications in patients with DM in Iran from 2013 to 2017. Methods This retrospective cross-sectional study was undertaken using prescription claims data from 2013 to 2017 in Iran. Epidemiological data elements used in this study were obtained from the Global Burden of Disease (GBD) 2019 study. In addition, data on total medication sales were obtained from the national regulatory authority database. The data on medication utilization were analyzed according to the Anatomical Therapeutic Chemical Classification (ATC) /Defined Daily Doses (DDD) international system. Results Based on the findings, Acetylsalicylic acid was the mainstay of treatment with a utilization rate of 191.7 DDD/ patient/ year in 2017, followed by Atorvastatin with 170.0 and Losartan with 115.1. Although there was an increasing trend in the utilization rate of the medications, the rate of Atenolol and Enalapril was constantly declining during the 2013-17 period. On the other hand, Valsartan and Metoprolol were attracting attention. Almost all medication utilization rates increased from the 30--39 age group up to the 80 + age group. Females had a higher utilization rate in each age group during the whole study period. Conclusion The present study reflects that medication utilization patterns were rational, according to the standard treatment guidelines. Utilization patterns of medications that are recommended for both prevention and treatment of CVD in diabetes were observed to be the highest. Implementation of further policies is needed to minimize cardiovascular complications of diabetes. [ABSTRACT FROM AUTHOR]

Beta‐blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age‐related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta‐blockers are associated with an increased risk of falls in older beta‐blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta‐blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B‐PROOF cohort. The associations between the beta‐blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11–2.16], p =.01). No association was found for nonselective beta‐blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta‐blockers users. This might be caused by a decreased β1‐selectivity in high plasma concentrations. In the future, beta‐blocker concentrations could potentially help clinicians estimate fall risk in older beta‐blockers users and personalize treatment. [ABSTRACT FROM AUTHOR]

Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in patients with reperfused acute myocardial infarction were equivocal. We, therefore, went back and tested the translational robustness of infarct size reduction by metoprolol in minipigs. Using a power analysis-based prospective design, we pretreated 20 anaesthetised adult Göttingen minipigs with 1 mg kg−1 metoprolol or placebo and subjected them to 60-min coronary occlusion and 180-min reperfusion. Primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was a secondary endpoint. There was no significant reduction in infarct size (46 ± 8% of area at risk with metoprolol vs. 42 ± 8% with placebo) or area of no-reflow (19 ± 21% of infarct size with metoprolol vs. 15 ± 23% with placebo). However, the inverse relationship between infarct size and ischaemic regional myocardial blood flow was modestly, but significantly shifted downwards with metoprolol, whereas ischaemic blood flow tended to be reduced by metoprolol. With an additional dose of 1 mg kg−1 metoprolol after 30-min ischaemia in 4 additional pigs, infarct size was also not reduced (54 ± 9% vs. 46 ± 8% in 3 contemporary placebo, n.s.), and area of no-reflow tended to be increased (59 ± 20% vs. 29 ± 12%, n.s.). Infarct size reduction by metoprolol in pigs is not robust, and this result reflects the equivocal clinical trials. The lack of infarct size reduction may be the result of opposite effects of reduced infarct size at any given blood flow and reduced blood flow, possibly through unopposed alpha-adrenergic coronary vasoconstriction. [ABSTRACT FROM AUTHOR]

Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 μg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video‐tracking software (ANY‐maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol‐exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol‐mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol‐exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido‐inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the influence of variables on dosage form development using a Taguchi orthogonal array design. By implementing the design, a total of nine sustained-release Metoprolol tartrate tablet formulations were created. In addition to four responses, four independent variables, including METHOCEL K15M, HPMC K100, Guar gum, and Pectic polysaccharide, were analyzed. In addition to evaluating formulations for hardness, swelling index, drug release percentage, and friability, a release kinetics study is conducted. Half normal plots and interaction plots were drawn to identify significant factors and study their interactions. The data were analyzed using statistical modeling, with the process order being design model and the model type being factorial with main effect determination. Formulation 'F1' was determined to be the best and most optimized formulation, and it was further characterized by attenuated total reflectance, differential scanning calorimetry, and X-ray diffraction studies. Additionally, the formulation was evaluated for stability in accordance with ICH guidelines, which revealed that it was sufficiently stable. [ABSTRACT FROM AUTHOR]

Background: Respiratory responses to extubation can cause serious postoperative complications. Beta-blockers, such as metoprolol, can interfere with the cough pathway. However, whether metoprolol can effectively control respiratory reflexes during extubation remains unclear. The objective of this study is to evaluate the efficacy of intravenous metoprolol in attenuating respiratory responses to tracheal extubation. Methods: Randomized, double-blinded, placebo-controlled trial. Setting: Tertiary referral center located in Brasília, Brazil. Recruitment: June 2021 to December 2021. Sample: 222 patients of both sexes with an American Society of Anesthesiologists (ASA) physical status I–III aged 18–80 years. Patients were randomly assigned to receive intravenous metoprolol 5 mg IV or placebo at the end of surgery. The primary outcome was the proportion of patients who developed bucking secondary to endotracheal tube stimulation of the tracheal mucosa during extubation. Secondary outcomes included coughing, bronchospasm, laryngospasm, Mean Blood Pressure (MAP), and Heart Rate (HR) levels. Results: Two hundred and seven participants were included in the final analysis: 102 in the metoprolol group and 105 in the placebo group. Patients who received metoprolol had a significantly lower risk of bucking (43.1% vs. 64.8%, Relative Risk [RR = 0.66], 95% Confidence Interval [95% CI 0.51–0.87], p = 0.003). In the metoprolol group, 6 (5.9%) patients had moderate/severe coughing compared with 33 (31.4%) in the placebo group (RR = 0.19; 95% CI 0.08–0.43, p < 0.001). Conclusion: Metoprolol reduced the risk of bucking at extubation in patients undergoing general anesthesia compared to placebo.

Here, we, for the first time, compared the cardioprotective effects of third-generation vasodilating beta-blocker nebivolol (Neb) and conventional beta-blocker metoprolol (Met) on LPS-induced injury in H9c2 cardiomyoblasts. Our findings denoted that Neb and Met pretreatment diminish LPS-mediated cytotoxicity and oxidative stress. Concomitantly, LPS-triggered inflammatory cytokines activation was significantly suppressed by Neb but not by Met. Pretreatment with either Neb or Met alleviated LPS-mediated mitochondrial impairment by enhancing the expression of genes related to its biogenesis such as PGC-1α, NRF1, and TFAM. On the contrary, Neb but not Met-upregulated mitochondrial fusion-related genes such as OPA, and MFN2. In summary, our findings suggest that Neb and Met treatment significantly ameliorated the LPS-induced cytotoxicity and oxidative stress. Additionally, these findings suggest that Neb but not Met significantly down-regulates LPS-induced proinflammatory factors, probably by enhancing mitochondrial biogenesis and fusion.

Abstract New, simple, accurate, sensitive and validated high performance thin layer chromatographic (HPTLC) method coupled with UV absorbance mode and fluorescence (FL) detectors which were used for simultaneous determination of ivabradine (IVA) and metoprolol (MET) in their bulk and pharmaceutical dosage form using TLC silica 60 F254 plates and non-fluorescent TLC silica gel 60 plates. The developing system was chloroform: methanol: formic acid: ammonia (8.5:1.5:0.2:0.1, v/v). Desnitometric analysis in UV absorbance mode was set at λ = 275 nm. While, fluorescence mode was performed with excitation at 260 nm for quantitative simultaneous determination of IVA and MET using optical filter K320. The retention factors values were 0.45 ± 0.05 and 0.89 ± 0.01 of IVA and MET, respectively. UV absorbance mode, linearity was 50.0–600.0 ng/band for IVA and 50.0–900.0 ng/band for MET. For fluorescence mode, the linearity ranges were 18.0–400.0 ng/band and 50.0–550.0 ng/band for IVA and MET; respectively. ICH guidelines were followed in respect to linearity and range, accuracy, precision and selectivity, limit of detection (LOD), limit of quantitation (LOQ) and robustness. The analytical eco-scale, green analytical procedure index (GAPI) and analytical greenness metric tools were used to assess the suggested method. The quantitative proposed method results showed there was no statistically significant difference at 95% confidence when compared to the reported method of high performance liquid chromatography (HPLC).

The study presents the case of a 47-year-old woman with type 2 diabetes (T2D), hypertension and anemia, treated with metformin, glyburide, metoprolol, and iron/folic acid. A drug interaction was identified between glyburide and metoprolol, causing symptoms of hypoglycemia in the afternoon. Evaluation using Horn’s Drug Interaction Probability Scale (DIPS) suggested a probable interaction. Pharmacokinetic analysis revealed that the time at which the maximum concentrations of both drugs were reached coincided with the onset of symptoms. A new medication schedule was implemented which resolved the symptoms. The drug interaction was attributed to the blockade of adrenergic effects by metoprolol, compromising the ability to counteract the action of insulin released by glybenclamide. The importance of surveillance, informed decision-making and the implementation of preventive strategies is highlighted to ensure the safety and effectiveness of pharmacological treatment in patients with specific clinical conditions, such as T2D and concomitant cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Metoprolol has been widely used for controlling high blood pressure, preventing myocardial reinfarction, setting rate changes, setting heart rhythm, treatment of chronic angina and preventing excessive bleeding during surgery. The purpose of this research is formulation and manufacture of extended release tablets of metoprolol succinate that conform to all the in vitro physicochemical US Pharmacopoeia national formulary (USP32). For preparing the tablets, the hydrophilic HPMC(K100M) polymer was used in direct compression method. Release of metoprolol in phosphate buffer having pH=6.8 (USP32) was measured by HPLC. Also, using experimental correlation of diffusivity in buffer medium and Gurney-Lurie charts during tablet enlargement with time, diffusion coefficients of drug and partition coefficients were obtained at different time steps. The rate of drug release depends on the type, viscosity and polymer concentration. Drug release results over 20 hours for polymers of HPMC(K100M), HPMC(K4M), HPMC(K15M), polyethylene oxide, ethyl cellulose, Eudragit (RL100) were investigated and compared. The results demonstrated that HPMC(K100M) met the standards of USP32 very well and was superior over the other polymers tested.

Abstract Beta‐blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age‐related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta‐blockers are associated with an increased risk of falls in older beta‐blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta‐blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B‐PROOF cohort. The associations between the beta‐blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11–2.16], p = .01). No association was found for nonselective beta‐blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta‐blockers users. This might be caused by a decreased β1‐selectivity in high plasma concentrations. In the future, beta‐blocker concentrations could potentially help clinicians estimate fall risk in older beta‐blockers users and personalize treatment.

Aims: Recent evidence supports non-class cardioprotective effects of metoprolol against neutrophil-mediated ischemia-reperfusion injury during exacerbated inflammation. Whether metoprolol exerts direct anti-inflammatory effect on cardiomyocytes is unknown. Accordingly, we aimed to investigate the direct anti-inflammatory effects of metoprolol in a cellular model of human induced pluripotent stem cell-derived cardiomyocytes (hiCMs) and to explore the role of β-arrestin2 (β-ARR2) biased agonism signaling pathway. Methods and results: hiCMs were treated with TNF-α for 24 h, followed by 4-hour treatment with metoprolol or esmolol. Electrical response of hiCMs to β1-selective blockade was assessed by microelectrode arrays technology. The effect on inflammatory and adhesion molecule expression was evaluated in wild-type and β-ARR2 silenced hiCMs. To silence β-ARR2 expression, hiCMs were transfected with a specific small interfering RNA targeting β-ARR2 mRNA and preventing its translation.TNF-α stimulation boosted the expression of IκB, NF-κB, IL1β, IL6, and VCAM1 in hiCMs. TNF-α-treated hiCMs showed similar physiological responses to metoprolol and esmolol, with no difference in field potential duration and beat period recorded. Adding metoprolol significantly decreased inflammatory response patterns in wild-type hiCMs by dampening TNF-α induced expression of NF-κB, IL1β, and IL6, but not in β-ARR2-knockout hiCMs. A similar response was not observed in presence of β1-selective blockade with esmolol. Conclusions: Metoprolol exerts a non-class direct anti-inflammatory effect on hi-CMs. β1-selective blockade with metoprolol disrupts inflammatory responses induced by TNF-α and induces significant inhibition of NF-κB signaling cascade via β-ARR2 biased agonism. If confirmed at clinical level, metoprolol could be tested and repurposed to treat cardiac inflammatory disorders.

Purpose: To study whether a Poincaré plot can help predict the curative effect of metoprolol for postural orthostatic tachycardia syndrome (POTS) in children. Methods: Pediatric patients with POTS who were administered metoprolol were retrospectively included. The collected data included general data (sex, age, height, weight, and body mass index), the manifestations and treatment (baseline orthostatic intolerance symptom score and course of metoprolol treatment), vital signs (supine heart rate [HR], supine blood pressure, and increased HR during the standing test), HR variability indexes (standard deviation of normal-to-normal intervals [SDNN]; standard deviation of the averages of normal-to-normal intervals [SDANN]; mean standard deviation of the NN intervals for each 5-min segment [SDNNI]; root mean square of the successive differences [rMSSD]; percentage of adjacent NN intervals that differ by >50 ms [pNN50]; triangular index; ultra-low [ULF], very low [VLF], low [LF], and high frequency [HF]; total power [TP]; and LF/HF ratio), and graphical parameters of the Poincaré plot (longitudinal axis [L], transverse axis [T], and L/T). Receiver operator characteristic curves were used to calculate the predictive function of the indexes with significant differences between patients who responded and those who did not. The index combination with the highest predictive value was obtained through series–parallel analysis. Results: Overall, 40 responders and 23 non-responders were included. The L and T in the Poincaré plots and rMSSD, pNN50, HF, and TP of the HR variability data were significantly lower in participants who responded to metoprolol than in participants who did not (p < 0.001). The L/T of participants who responded to metoprolol was greater than that of non-responders (p < 0.001). Moreover, we noted a strong correlation between every two indexes among L, T, rMSSD, pNN50, HF, TP, and L/T (p < 0.05). T < 573.9 ms combined with L/T > 2.9 had the best performance for predicting the effectiveness of metoprolol, with a sensitivity of 85.0%, specificity of 82.6%, and accuracy of 84.1%. Conclusion: In the Poincaré plot, a T < 573.9 ms combined with an L/T > 2.9 helps predict good outcomes of using metoprolol to treat pediatric POTS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. β-Adrenergic receptor antagonists (β-blockers) are the first-line therapy for HCM. However, β-blockers commonly selected for this disease are often poorly tolerated in patients, where heart-rate reduction and noncardiac effects can lead to reduced cardiac output and fatigue. Mavacamten, myosin ATPase inhibitor recently approved by the US Food and Drug Administration, has demonstrated the ability to ameliorate hypercontractility without lowering heart rate, but its benefits are so far limited to patients with left ventricular (LV) outflow tract obstruction, and its effect on arrhythmia is unknown. METHODS: We screened 21 β-blockers for their impact on myocyte contractility and evaluated the antiarrhythmic properties of the most promising drug in a ventricular myocyte arrhythmia model. We then examined its in vivo effect on LV function by hemodynamic pressure–volume loop analysis. The efficacy of the drug was tested in vitro and in vivo compared with current therapeutic options (metoprolol, verapamil, and mavacamten) for HCM in an established mouse model of HCM (Myh6R403Q/+ and induced pluripotent stem cell (iPSC)-derived cardiomyocytes from patients with HCM (MYH7R403Q/+). RESULTS: We identified that carvedilol, a β-blocker not commonly used in HCM, suppresses contractile function and arrhythmia by inhibiting RyR2 (ryanodine receptor type 2). Unlike metoprolol (a β1-blocker), carvedilol markedly reduced LV contractility through RyR2 inhibition, while maintaining stroke volume through α1-adrenergic receptor inhibition in vivo. Clinically available carvedilol is a racemic mixture, and the R-enantiomer, devoid of β-blocking effect, retains the ability to inhibit both α1- receptor and RyR2, thereby suppressing contractile function and arrhythmias without lowering heart rate and cardiac output. In Myh6R403Q/+ mice, R-carvedilol normalized hyperdynamic contraction, suppressed arrhythmia, and increased cardiac output better than metoprolol, verapamil, and mavacamten. The ability of R-carvedilol to suppress contractile function was well retained in MYH7R403Q/+ iPSC-derived cardiomyocytes. CONCLUSIONS: R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and at the same time, improves cardiac output without lowering heart rate by dual blockade of α1-adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction. [ABSTRACT FROM AUTHOR]

New, simple, accurate, sensitive and validated high performance thin layer chromatographic (HPTLC) method coupled with UV absorbance mode and fluorescence (FL) detectors which were used for simultaneous determination of ivabradine (IVA) and metoprolol (MET) in their bulk and pharmaceutical dosage form using TLC silica 60 F254 plates and non-fluorescent TLC silica gel 60 plates. The developing system was chloroform: methanol: formic acid: ammonia (8.5:1.5:0.2:0.1, v/v). Desnitometric analysis in UV absorbance mode was set at λ = 275 nm. While, fluorescence mode was performed with excitation at 260 nm for quantitative simultaneous determination of IVA and MET using optical filter K320. The retention factors values were 0.45 ± 0.05 and 0.89 ± 0.01 of IVA and MET, respectively. UV absorbance mode, linearity was 50.0–600.0 ng/band for IVA and 50.0–900.0 ng/band for MET. For fluorescence mode, the linearity ranges were 18.0–400.0 ng/band and 50.0–550.0 ng/band for IVA and MET; respectively. ICH guidelines were followed in respect to linearity and range, accuracy, precision and selectivity, limit of detection (LOD), limit of quantitation (LOQ) and robustness. The analytical eco-scale, green analytical procedure index (GAPI) and analytical greenness metric tools were used to assess the suggested method. The quantitative proposed method results showed there was no statistically significant difference at 95% confidence when compared to the reported method of high performance liquid chromatography (HPLC). [ABSTRACT FROM AUTHOR]

Introduction-Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after heart surgery. The present study was conducted to study the use of metoprolol in pre and post isolated CABG cases to reduce the incidence of atrial fibrillation. Material and methods- 50 cases and controls who had undergone isolated CABG surgery with extracorporeal circulation participated in a randomised research. The administration of metoprolol orally to the patients during the postoperative phase was randomised. The results included the identification of persistent arrhythmia that was symptomatic or needed medical attention. Patients having baseline left ventricular ejection fractions less than 35%, prior episodes of AF, a history of bronchospasm, second- and third-degree atrioventricular blocks, inadequate cardiac output, and heart failure were excluded from the trial. Results- In the metoprolol group, 10% patients experienced arrhythmias, compared to 23% in the control group (P=0.03). The arrhythmia that was seen the most commonly (85%) was AF. Arrhythmias occurred in 52% metoprolol-treated patients and 56% control patients among patients aged 70 or older with the 95% confidence interval for the risk was 0.10. Conclusion- In the postoperative period following CABG surgery, metoprolol is useful in reducing arrhythmia, and this effect was especially noticeable in the group of senior patients. [ABSTRACT FROM AUTHOR]

The article describes the case of a 55-year-old man with arrhythmogenic cardiomyopathy with biventricular involvement who was referred for subcutaneous defibrillator (S-ICD) removal and dual chamber implantable cardioverter defibrillator (ICD) implanation. Topics discussed include his left ventricular ejection fraction on echocardiography, his medical therapy, and advantage of antitachycardia pacing (ATP) offered by transvenous ICDs over S-ICDs.

Nowadays, it is a challenge for a bone scaffold to achieve controllable drug release and a porous structure at the same time. Herein, we fabricated hydroxyapatite/poly (butylene succinate)/metoprolol tartrate (HA/PBS/MPT) composites via melt blending, aiming to provide the option of an in situ pore-forming strategy. The introduction of HA not only significantly improved the hydrophilicity of the PBS matrix by reducing the hydrophilic contact angle by approximately 36% at a 10% content, but also damaged the integrity of the PBS crystal. Both were beneficial for the penetration of phosphate-buffered saline solution into matrix and the acceleration of MPT release. Accompanied with MPT release, porous structures were formed in situ, and the HA inside the matrix was exposed. With the increase in HA content, the MPT release rate accelerated and the pore size became larger. The in vitro cytocompatibility evaluation indicated that HA/PBS/MPT composites were conductive to the adhesion, growth, and proliferation of MC3T3-E1 cells due to the HA being exposed around the pores. Thus, the MPT release rate, pore size, and cell induction ability of the HA/PBS/MPT composites were flexibly and effectively adjusted by the composition at the same time. By introducing HA, we innovatively achieved the construction of porous structures during the drug release process, without the addition of pore-forming agents. This approach allows the drug delivery system to combine controllable drug release and biocompatibility effectively, offering a novel method for bone repair material preparation. This work might provide a convenient and robust strategy for the fabrication of bone scaffolds with controllable drug release and porous structures. [ABSTRACT FROM AUTHOR]

This research was designed to unveil the impacts of percutaneous coronary intervention via transradial artery access (TRA-PCI) combined with metoprolol on cardiac function and vascular endothelial function in elderly patients with coronary heart disease (CHD). Collectively, 112 CHD patients were enrolled and allocated into a control group (patients treated with TRA-PCI) and an observation group (patients treated with TRA-PCI and metoprolol) following the random number table method (n = 56 patients). The treatment outcome, cardiac function indicators, serum inflammatory factor indicators, vascular endothelial function indicators, and the occurrence of coronary restenosis were compared between the two groups. After treatment, elevated total effective rate was noted in CHD patients treated with TRA-PCI and metoprolol in contrast to TRA-PCI treatment alone. CHD patients treated with TRA-PCI and metoprolol alleviated cardiac function and vascular endothelial function and reduced inflammatory response and the occurrence of coronary restenosis in comparison to TRA-PCI treatment alone. TRA-PCI combined with metoprolol is effective in improving cardiac function and endothelial function, and reducing the degree of inflammation in the body and the occurrence of coronary restenosis in CHD patients. [ABSTRACT FROM AUTHOR]

This study describes the systematic development of a high-performance thin-layer chromatography (HPTLC) method for the quantification of amlodipine besylate (AML), metoprolol succinate (MET), and telmisartan (TEL) in synthetic mixture within the quality by design framework. A mixture of toluene‒methanol‒isopropanol‒triethylamine (6:0.8:2:0.2, V/V) was used as the mobile phase for chromatographic separation on aluminum-backed silica gel 60 F254 plates with densitometric scanning at 233 nm. The effects of identified critical method parameters, volume of methanol, chamber saturation duration, and solvent front on the RF value of all three drugs and resolution between two drugs were investigated using Box‒Behnken experimental design. To understand potential interactions among critical method parameters, statistical modelization was used, followed by response surface analysis. By using numerical and graphical optimization to define the design space, the search for the best solution was carried out. The RF values discovered after optimization for AML, MET, and TEL were 0.25, 0.39, and 0.48, respectively. The calibration plots' data from the linear regression analysis indicated a regression coefficient more than 0.99 for a concentration range of 500–2500 ng/band for AML, 400–2000 ng/band for MET, and 100–500 ng/band for TEL. The optimized HPTLC method was validated according to the International Council for Harmonisation (ICH) guideline Q2 (R1). The %RSD for accuracy, precision, and robustness were all within the acceptable range, less than 2. Additionally, the AGREE greenness assessment tool was used to analyze the greenness profile of the developed method, the score of 0.79 proved that the technique is environmentally friendly and can be regularly used for the analysis of all three drugs in combination. The investigations effectively show the applicability of the quality by design (QbD) strategy in the development of the highly sensitive HPTLC method with improved method performance. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study on the trend of beta-blocker doses in various age groups among older people with heart failure with reduced ejection fraction (HFrEF). Also cited are the use of the Medicare Fee-for-Service (FFS0 claims data in the study, and the recommended target doses from the 2013 American College of Foundation/American Heart Association for HF management.

The primary objective of this study was to assess the potential utility of quince seed mucilage as an excipient within a graft copolymer for the development of an oral-controlled drug delivery system. The Cydonia oblonga-mucilage-based graft copolymer was synthesized via a free radical polymerization method, employing potassium per sulfate (KPS) as the initiator and N, N-methylene bisacrylamide (MBA) as the crosslinker. Various concentrations of monomers, namely acrylic acid (AA) and methacrylic acid (MAA), were used in the graft copolymerization process. Metoprolol tartarate was then incorporated into this graft copolymer matrix, and the resultant drug delivery system was subjected to comprehensive characterization using techniques such as Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The swelling behavior of the drug delivery system was evaluated under different pH conditions, and in vitro drug release studies were conducted. Furthermore, pharmacokinetic parameters including the area under the curve (AUC), maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and half-life (t1/2) were determined for metoprolol-loaded hydrogel formulations in rabbit plasma, and these results were compared with those obtained from a commercially available product. The key findings from the study include observations that higher concentrations of acrylic acid (AA) and Cydonia oblonga mucilage (CM) in the graft copolymer enhanced swelling, while the opposite trend was noted at elevated concentrations of methacrylic acid (MAA) and N, N-methylene bisacrylamide (MBA). FTIR analysis confirmed the formation of the graft copolymer and established the compatibility between the drug and the polymer. SEM imaging revealed a porous structure in the prepared formulations. Additionally, the swelling behavior and drug release profiles indicated a pH-sensitive pattern. The pharmacokinetic assessment revealed sustained release patterns of metoprolol from the hydrogel network system. Notably, the drug-loaded formulation exhibited a higher Cmax (156.48 ng/mL) compared to the marketed metoprolol product (96 ng/mL), and the AUC of the hydrogel-loaded metoprolol was 2.3 times greater than that of the marketed formulation. In conclusion, this study underscores the potential of quince seed mucilage as an intelligent material for graft-copolymer-based oral-controlled release drug delivery systems. [ABSTRACT FROM AUTHOR]

Small studies suggest that amiodarone is a weak inhibitor of cytochrome P450 (CYP) 2D6. Inhibition of CYP2D6 leads to increases in concentrations of drugs metabolized by the enzyme, such as metoprolol. Considering that both metoprolol and amiodarone have β‐adrenergic blocking properties and that the modest interaction between the two drugs would result in increased metoprolol concentrations, this could lead to a higher risk of bradycardia and atrioventricular block. The primary objective of this study was to evaluate whether metoprolol plasma concentrations collected at random timepoints from patients enrolled in the Montreal Heart Institute Hospital Cohort could be useful in identifying the modest pharmacokinetic interaction between amiodarone and metoprolol. We performed an analysis of a cross‐sectional study, conducted as part of the Montreal Heart Institute Hospital Cohort. All participants were self‐described "White" adults with metoprolol being a part of their daily pharmacotherapy regimen. Of the 999 patients being treated with metoprolol, 36 were also taking amiodarone. Amiodarone use was associated with higher metoprolol concentrations following adjustment for different covariates (p =.0132). Consistently, the association between amiodarone use and lower heart rate was apparent and significant after adjustment for all covariates under study (p =.0001). Our results highlight that single randomly collected blood samples can be leveraged to detect modest pharmacokinetic interactions. [ABSTRACT FROM AUTHOR]

Copyright of Saudi Medical Journal is the property of Saudi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cardiac Kv4.3 channels contribute to the transient outward K+ current, Ito, during early repolarization of the cardiac action potential. Two different isoforms of Kv4.3 are present in the human ventricle and exhibit differential remodeling in heart failure (HF). Cardioselective betablockers are a cornerstone of HF with reduced ejection fraction therapy as well as ventricular arrhythmia treatment. In this study we examined pharmacological effects of betablockers on both Kv4.3 isoforms to explore their potential for isoform-specific therapy. Kv4.3 isoforms were expressed in Xenopus laevis oocytes and incubated with the respective betablockers. Dose-dependency and biophysical characteristics were examined. HEK 293T-cells were transfected with the two Kv4.3 isoforms and analyzed with Western blots. Carvedilol (100 µM) blocked Kv4.3 L by 77 ± 2% and Kv4.3 S by 67 ± 6%, respectively. Metoprolol (100 µM) was less effective with inhibition of 37 ± 3% (Kv4.3 L) and 35 ± 4% (Kv4.3 S). Bisoprolol showed no inhibitory effect. Current reduction was not caused by changes in Kv4.3 protein expression. Carvedilol inhibited Kv4.3 channels at physiologically relevant concentrations, affecting both isoforms. Metoprolol showed a weaker blocking effect and bisoprolol did not exert an effect on Kv4.3. Blockade of repolarizing Kv4.3 channels by carvedilol and metoprolol extend their pharmacological mechanism of action, potentially contributing beneficial antiarrhythmic effects in normal and failing hearts. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to examine the effects of orally administered metoprolol on the frequency and severity of pain caused by rocuronium injection in patients who started to use and were currently using oral metoprolol for any reason such as ischemic heart disease, hypertension, and arrhythmias. Methods: Patients were evaluated in four groups. Group M: patients currently using metoprolol and who did not receive lidocaine before the application of rocuronium. Group ML: patients currently using metoprolol and who received lidocaine before rocuronium application. Group L: patients currently not using metoprolol and received lidocaine before rocuronium application. Group C: patients currently not using metoprolol and who did not receive lidocaine before rocuronium application. Following the induction of general anesthesia with thiopental sodium, a researcher blind to the groups observed the pain during rocuronium injection based on the following scale: (1) no reaction, (2) movement only in the ankle, (3) movement or withdrawal only in the arm (shoulder and ankle), and (4) diffuse reaction (movement or withdrawal in more than one extremity, coughing and holding breath). Results: Two hundred patients with 50 in each of four groups were included. The incidence of pain was statistically significantly lower in Group ML compared to Groups M and C (p = 0.001). The correlations between pain caused by rocuronium injection and duration of metoprolol usage and the time since the last dose were not statistically significant (for all, p > 0.05). Conclusions: Oral metoprolol combined with lidocaine reduced pain and withdrawal reflex caused by rocuronium injection. No significant difference was observed between the last dose and the duration of metoprolol usage. [ABSTRACT FROM AUTHOR]

The use of the USP IV apparatus (flow-through cell) has gained acceptance in recent years due to its versatility and ability to discriminate due to its hydrodynamic conditions. Therefore, the objective of the present study was to develop a discriminative dissolution method in the USP IV apparatus using the open-loop configuration, as well as to propose a method to compare non-cumulative dissolution profiles obtained in the open-loop configuration considering kinetic parameters and validate its predictive power through its comparison with independent and dependent methods using five commercial immediate-release tablet drugs (one reference drug and four generic drugs) of metoprolol tartrate as a model drug. The comparison of the non-accumulated dissolution profiles consisted of determining the geometric ratio of Cmax, AUC0∞, AUC0Cmax, and Tmax (kinetic parameters) of the generic/reference drugs, whereby generic drugs "C" and "D" presented the highest probability of similarity since their 90% confidence intervals were included, or they were very close to the acceptance interval (80.00–125.00%). These results were consistent with the f2, bootstrap f2, and dissolution efficiency approaches (independent models). In conclusion, the proposed comparison method can be an important tool to establish similarity in dissolution profiles and to facilitate the development/selection of new formulations and positively ensure bioequivalence in clinical studies. [ABSTRACT FROM AUTHOR]

The aim of this study is to design and evaluate metoprolol succinate sustained release (SR) matrix tablets employing a natural gum blend as the rate-retarder. Developing a tablet matrix utilizing locust bean gum (LBG), xanthan gum (XG), and guar gum (GG) was done to aid metoprolol succinate release over a 24-h period and help in once-daily dosage, reducing nocturnal episodes in hypertensive patients. In an effort to create a synergistic effect, attempts were made to combine commonly used natural gums, XG and GG, with LBG, which served as the primary release-retardant. The optimal way to formulate the tablet was studied using polymer blend ratios of 1:1, 1:3, 1:5, 1:1:1, 1:2:1 and 1.5:1.5:1. The same created polymer mix was used as the binding agent to prepare tablets utilizing the wet granulation process. Weight, thickness, hardness, content homogeneity, in-vitro drug release, erosion, and water uptake were used to characterize the formulations. Additional testing for drug-excipient compatibility was conducted. It was discovered that an XG:LBG:GG ratio of 1:2:1 produced the best outcomes having the highest t75% of cumulative drug release of 15.2 h, outperforming commercial formulations. A relation between the gum concentration and release rate retarding effect was also established. 3.33% of gum concentration showed optimal sustained release effects. The results concluded that the prepared SR metoprolol succinate tablets might be one of the best formulation for hypertensive patients that not only serves therapeutic purpose but also values the patients concern of providing minimal side-effect in the long run use of the medication. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to investigate the effects of ivabradine (IVA) on ventricular electrophysiological remodeling after myocardial infarction (MI) in rats. Material and methods: A total of 60 male Sprague-Dawley rats were randomly divided into five groups: an MI group, an IVA group, a metoprolol (MET) group, an IVA + MET group, and a sham group. After a four-week intervention, the ventricular electrophysiological parameters were detected by multichannel electrophysiological polygraph. Then, the morphological characteristics were evaluated using hematoxylin and eosin (H&E) and Masson's staining, and the expression of phosphorylated connexin 43 (p-Cx43) in the left ventricular wall was detected through immunohistochemistry and the Western blot test. Results: The electrophysiological examination revealed that the induction rate and fatality rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) were lower in both the IVA and the MET group, compared with the MI group (6/12, 6/12 vs. 10/11; and 1/12, 1/12 vs. 5/11; all p < 0.05), as well as the IVA + MET group (1/11 vs. 10/11, p < 0.01; and 1/11 vs. 5/11, p < 0.05). The induction rate of VT/VF was lower in the IVA + MET group, compared to the MET group (1/11 vs. 6/12, p < 0.05). H&E and Masson's staining revealed that compared with the MI group, the left ventricular infarction area was lower in the IVA, MET, and IVA + MET groups (p < 0.05, p < 0.05, and p < 0.01, respectively), while collagen volume fraction (CVF) also was lower in the other groups (all p < 0.01). The left ventricular infarction area and CVF both were lower in the IVA + MET group, compared to the MET group (p < 0.05 and p < 0.01, respectively). The immunohistochemistry and Western blot revealed that p-Cx43 expression was higher in the treatment groups, compared with the MI group (all p < 0.01). Conclusions: IVA can reduce the incidence of ventricular arrhythmia after MI in male rats by improving both structural and electrical remodeling, and the combination of IVA and MET is even more effective. [ABSTRACT FROM AUTHOR]