Search Results (131)

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

Aims: Sinus tachycardia after heart transplantation (HTX) due to cardiac graft denervation is associated with reduced post-transplant survival and requires adequate treatment. We analyzed the long-term effects of heart rate control with ivabradine or metoprolol succinate in HTX recipients. Methods: This observational retrospective single-center study analyzed the ten-year results of 110 patients receiving ivabradine (n = 54) or metoprolol succinate (n = 56) after HTX. Analysis included comparison of demographics, medications, heart rates, blood pressure values, echocardiographic features, cardiac catheterization data, cardiac biomarkers, and post-transplant survival including causes of death. Results: Both groups showed no significant differences concerning demographics or medications (except for ivabradine and metoprolol succinate). At 10-year follow-up, HTX recipients with ivabradine showed a significantly lower heart rate (72.7 ± 8.5 bpm) compared to baseline (88.8 ± 7.6 bpm; p < 0.001) and to metoprolol succinate (80.1 ± 8.1 bpm; p < 0.001), a significantly lower NT-proBNP level (588.4 ± 461.4 pg/mL) compared to baseline (3849.7 ± 1960.0 pg/mL; p < 0.001) and to metoprolol succinate (1229.0 ± 1098.6 pg/mL; p = 0.005), a significantly lower overall mortality (20.4% versus 46.4%; p = 0.004), and mortality due to graft failure (1.9% versus 21.4%; p = 0.001). Multivariate analysis showed a significantly decreased risk of death within 10 years after HTX in patients with post-transplant use of ivabradine (HR 0.374, CI 0.182–0.770; p = 0.008). Conclusions: In this single-center trial, patients with ivabradine revealed a significantly more pronounced heart rate reduction, a lower NT-proBNP level, and a superior 10-year survival after HTX. Full article

In response to the European Union’s revised Urban Wastewater Treatment Directive, which mandates enhanced monitoring and advanced treatment of micropollutants, this study was conducted. It took place within the Coastal Landscape Park (CLP), a Natura 2000 protected area in northern Poland. The focus was on the municipal wastewater treatment plant in Jastrzębia Góra, located in a region exposed to seasonal tourist pressure and discharging effluent into the Czarna Wda River. A total of 90 wastewater samples were collected during five monitoring campaigns (July, September 2021; February, May, July 2022) and analysed for 13 pharmaceuticals and personal care products (PPCPs) using ultra-high-performance liquid chromatography tandem mass spectrometry with electrospray ionisation (UHPLC-ESI-MS/MS). The monitoring included both untreated (UTWW) and treated wastewater (TWW) to assess the PPCP removal efficiency and persistence. The highest concentrations in the treated wastewater were observed for metoprolol (up to 472.9 ng/L), diclofenac (up to 3030 ng/L), trimethoprim (up to 603.6 ng/L) and carbamazepine (up to 2221 ng/L). A risk quotient (RQ) analysis identified diclofenac and LI-CBZ as priority substances for monitoring. Multivariate analyses (PCA, HCA) revealed co-occurrence patterns and seasonal trends. The results underline the need for advanced treatment solutions and targeted monitoring, especially in sensitive coastal catchments with variable micropollutant presence. Full article

Background: Acute kidney injury (AKI) in critically ill patients is often complicated by arrhythmias, potentially affecting outcomes. This study aimed to develop predictive models for arrhythmias in AKI patients and assess the impact of antiarrhythmic drugs on in-hospital mortality. Methods: We conducted a multi-database retrospective cohort study using MIMIC-IV and eICU databases. XGBoost and Bayesian Information Criterion (BIC) models were employed to identify key predictors of arrhythmias. Weighted log-rank and Cox analysis evaluated the effect of amiodarone and metoprolol on in-hospital mortality. Results: Among 14,035 critically ill AKI patients, 5614 individuals (40%) developed arrhythmias. Both XGBoost and BIC showed predictive power for arrhythmias. The XGBoost model identified HR_max, HR_min, and heart failure as the most important features, while the BIC model highlighted heart failure had the highest odds ratio (OR 1.18, 95% CI 1.16–1.20) as a significant predictor. Patients experiencing arrhythmia is associated with in-hospital mortality (arrhythmia group: 636 (11.3%) vs. non-arrhythmia group: 587 (7.0%), p < 0.01). Antiarrhythmic medications showed a statistically significant effect on in-hospital mortality (amiodarone: HR 0.28, 95% CI 0.19–0.41, p < 0.01). Conclusions: Our predictive models demonstrated a robust discriminatory ability for identifying arrhythmia occurrence in critically ill AKI patients, with identified risk factors showing strong clinical relevance. The significant association between arrhythmia occurrence and increased in-hospital mortality underscores the clinical importance of early identification and management. Furthermore, amiodarone therapy effectively reduced the risk of in-hospital mortality in these patients, even after accounting for time-dependent biases. The findings highlight the necessity of precise arrhythmia definition, careful consideration of time-dependent covariates, and comprehensive model validation for clinically actionable insights. Full article

The current paper examines the sustainable possibility for recycling unused or expired Metoprolol (MET), a benzodiazepine derivative, as an effective corrosion inhibitor for carbon steel in saline solutions. Repurposing expired medicinal drugs aligns with green chemistry concepts and supports circular economy initiatives by reducing pharmaceutical waste and averting the production of new synthetic inhibitors. The technical benefit of recycling expired MET drugs pertains to the elimination of costs associated with organic inhibitor manufacturing and the decrease in disposal expenses for the expired medication. A combination of electrochemical techniques (potentiodynamic polarization and electrochemical impedance spectroscopy) and quantum chemical calculations was employed to evaluate the inhibitory mechanism and efficacy of MET. At a concentration of 10⁻³ M, MET reduced the corrosion current density from 19.38 to 5.97 μA cm⁻², achieving a maximum IE of 69.1%. Adsorption Gibbs free energy, determined using different adsorption isotherms, revealed that interactions between metal atoms and MET adsorbed molecules have a chemical character with a ∆G^o_ads value of −50.7 kJ·mol⁻¹. Furthermore, quantum chemistry calculations indicate that the investigated drug, owing to its molecular structure (E_HOMO = −9.12 eV, E_LUMO = 0.21 eV, µ = 3.95 D), possesses the capacity to establish an adsorption layer on the metal surface, thereby impeding the diffusion of molecules and ions involved in the overall corrosion process. The results obtained using the different techniques were in good agreement and highlighted the effectiveness of MET in the corrosion inhibition of carbon steel. Full article

Hypertension disorders of pregnancy affect almost 10% of pregnancies. Most hypertensive disorders associated with pregnancy, including chronic hypertension and gestational hypertension, often persist into the postpartum period. Thus, many breastfeeding mothers require ongoing antihypertensive treatment with antihypertensive medications while nursing. This highlights the importance of understanding the efficacy, safety, and potential adverse effects of antihypertensive therapy in breastfeeding mothers. Unfortunately, research in this area is limited, and references in clinical guidelines remain sparse. Our review aims to provide a comprehensive summary of the current knowledge on antihypertensive medications during breastfeeding, drawing from available research and evidence-based guidelines. This article discusses all groups of antihypertensive drugs, presenting societies’ recommendations and available clinical data. Based on the available literature, calcium channel blockers (extended-release nifedipine as the first choice) and beta-blockers (labetalol, metoprolol) appear to be the drugs of choice. Our review highlights the need for further research to evaluate the long-term safety of antihypertensive medications during breastfeeding, improve clinical guidelines, and ensure optimal treatment for nursing mothers. Full article

The antihypertensive drugs indapamide, atenolol, metoprolol, propranolol and bisoprolol were considered in this research. Because they have structures that are affected by pH, developing a chromatographic method was challenging. Based on the speciation diagram of these compounds versus pH scale, a mixed-mode stationary phase (hydrophobic stationary phase, C18 and strong cation exchanger (SCX)) was our first choice. Design of Experiments (DoE) was used to estimate how various factors such as pH, mobile phase composition and flow rate influenced chromatographic performance. As a result, the separation was achieved in 24 min using an aqueous phosphate buffer phase (pH 7.20) and 20 mM triethylamine, with methanol being used as organic modifier (30%). Their retention mechanism was investigated. The new method was validated in term of linearity, limits of detection and quantification, precision, accuracy, and robustness. The method was applied to river water samples, and good results were obtained. Full article

Background: Permanent atrial fibrillation (AF) frequently coexists with heart failure (HF), leading to structural remodeling and progressive sinus node dysfunction. As the condition advances, bradyarrhythmia or tachy-brady syndrome may develop. Right ventricular pacing and cardiac resynchronization therapy may impair left ventricular function due to non-physiological ventricular activation. His bundle pacing (HBP) offers a more physiological alternative. This study evaluates HBP’s impact on left ventricular function in patients with bradyarrhythmia or tachy-brady syndrome and permanent AF. Methods: A retrospective analysis included 41 patients with HF who underwent HBP implantation due to bradyarrhythmia or tachy-brady syndrome in permanent AF. LVEF, LVEDD, and MR were assessed before and after implantation, alongside the impact of comorbidities (e.g., ischemic heart disease and chronic kidney disease) and pharmacotherapy (digoxin, metoprolol, and mineralocorticoid receptor antagonists). Statistical analyses included the Wilcoxon test (LVEF and MR), paired Student’s t-test (LVEDD), Spearman’s correlation, and linear regression. Significance was set at p < 0.05. Results: HBP significantly improved LVEF (median increase: 14.58%; p < 0.001) and reduced LVEDD (mean reduction: 5.41 ± 1.30 mm; p < 0.001). MR severity also decreased (p < 0.001). Patients with lower baseline LVEF showed greater improvement in this parameter after HBP (ρ = −0.671, p < 0.001). Only chronic kidney disease was associated with a lower likelihood of MR improvement (p = 0.0486). Conclusions: HBP improves left ventricular function and reduces MR severity in patients with permanent AF and bradyarrhythmia or tachy-brady syndrome. A low baseline LVEF was the strongest predictor of subsequent improvement. Further studies are needed to confirm long-term benefits. Full article

Beta-blockers are pharmaceuticals used to treat cardiovascular diseases such as hypertension, angina pectoris, and arrhythmia. Due to high consumption, they are continuously released into the environment, being detected in many aqueous matrices. The aim of this research is to test the effectiveness of two green liquid-phase microextraction procedures, such as dispersive liquid–liquid microextraction (DLLME) and solidification of floating organic droplet microextraction (SFOME) for the selective extraction of eight beta-blockers (atenolol, nadolol, pindolol, acebutolol, metoprolol, bisoprolol, propranolol, and betaxolol) from aqueous matrices for their analysis by gas chromatography (GC) or liquid chromatography (LC). The influence of extraction parameters, such as the type and volume of extraction and disperser solvents, and ionic strength were studied. The developed extraction procedures provide a good enrichment factor for six compounds (61.22–243.97), good extraction recovery (53.04–92.1%), and good sample cleaning for both extraction procedures. Good limits of detection (0.13 to 0.69 µg/mL for GC and 0.07 to 0.15 µg/mL for HPLC) and limits of quantification (0.39 to 2.10 µg/mL for GC and 0.20 to 0.45 µg/mL for LC) were obtained. The developed procedures were successfully applied to the analysis of selected beta-blockers in wastewater samples, proving their applicability to the real samples. Full article

Complete atrioventricular (AV) block is a severe conduction abnormality caused by intrinsic cardiac disease, ischemia, electrolyte imbalances, or drug interactions. Elderly patients on multiple medications are particularly vulnerable to polypharmacy-related interactions. This case report describes an 82-year-old female presenting to the emergency department with fatigue, syncope, and disorientation. Her medical history included atrial fibrillation, hypertension, and heart failure, with a medication regimen of digoxin 0.25 mg given daily 5 days out of 7, metoprolol 50 mg twice daily, lisinopril 10 mg daily, furosemide 40 mg daily, and spironolactone 50 mg daily. Clinical examination revealed bradycardia and a holosystolic murmur in the mitral valve area, while the electrocardiogram showed complete AV block at a ventricular rate of 35 bpm. Laboratory results indicated mild hyperkalemia (4.9 mmol/L). Suspecting a digoxin–beta-blocker interaction, antiarrhythmic therapy was discontinued. Within three days, the AV block resolved, transitioning to atrial fibrillation with a high ventricular rate. Bisoprolol was introduced for rate control, and hemodynamic stability was achieved. The patient was discharged with a revised medication regimen and showed no recurrence of AV block. This case emphasizes the importance of recognizing drug interactions as a reversible cause of AV block and using drug interaction checkers to manage polypharmacy, especially in elderly patients with multiple comorbidities. It also highlights the rare and paradoxical combination of atrial flutter and complete AV block. Full article

Background/Objectives: Some specific types of white blood cells (WBCs) and the neutrophil/lymphocyte ratio (NLR) are independent predictors of outcome for heart failure (HF) patients. WBC redistribution is induced by catecholamines, and therefore we evaluate how different types of beta-blockers (BBs) influence it. Methods: The HF patients were clinically evaluated, and blood was drawn to measure N-Terminal pro–B-type natriuretic peptide (NT-proBNP), WBC-differential formula, etc. Results: On admission, 61.16% of patients who used a BB had no significant difference in the number of lymphocytes (Lym) and neutrophils (Neu), but NLR and NT- proBNP were significantly lower compared with those without BB. NT-proBNP correlated with BB dose on admission and was significantly lower in patients treated with Metoprolol (Met) as compared with Carvedilol (Car). The type and dose of BB used was responsible for 6.1% and 5.9% of the variability in the number of Lym and Neu, respectively. Patients treated with ≥100 mg Met/day had a higher Lym number, but not of Neu, with reduced NLR, compared with lower doses. Patients treated with ≥25 mg Car/day had a lower Lym number and a greater Neu number, compared with lower doses, with increased NLR. Conclusions: However, both BBs had the same rehospitalization rate during the 12 month follow-up and had an improved outcome. Full article

As an ideal carrier for the spread of pollutants in the aquatic environment, microplastics (MPs) can adsorb pharmaceutical β-blockers, which can affect their migration and lead to some unpredictable adverse consequences. In this paper, the sorption behaviors and mechanism of MPs (polyvinyl chloride (PVC) and polypropylene (PP)) for typical β-blocker metoprolol (MTL) were investigated. The effects of pH, salinity and humic acids (HAs) on the sorption were studied, which proved that the sorption behavior was different under different environmental conditions. Both low pH and high salinity inhibited the sorption of MTL by the MPs. Specifically, the sorption capacity of MTL increased, with pH increase from 3 to 10. When pH = 10, the sorption capacities of MTL on PVC (1.75 mg/g) and PP (3.34 mg/g) reached the maximum. After pH > 10, the amount of MTL adsorbed on PVC was slightly decreased, while that on PP was essentially the same. The addition of salt ions inhibited the sorption in the concentration range of 5–250 mg/g for both NaCl and CaCl₂, with the inhibitory effect of Ca²⁺ being stronger than that of Na⁺. Moreover, the presence of HAs promoted the sorption of MPs for MTL. In the absence of HAs, the sorption capacities of PP and PVC for MTL were 0.34 mg/g and 0.79 mg/g, respectively. When HA concentration was 100 mg/L, the highest sorption capacities of PP and PVC reached 0.79 mg/g and 1.37 mg/g, respectively. This indicated that the promoting effect of HAs on PP was stronger than that on PVC. In general, based on the study of the sorption behavior of MTL and the characterization of the MPs, the sorption mechanism was speculated to consist mainly of electrostatic interactions, cation exchange, hydrophobic interaction and halogen bonding. The sorption kinetics of MTL on the two MPs were well-fitted by the pseudo-second-order model with R² > 0.99. The sorption isotherms both fitted the Freundlich model, which substantiated that the sorption of MTL on the MPs (PVC and PP) was multilayered and heterogeneous. Collectively, these findings provided a theoretical basis for revealing the complex interactions between MPs and MTL in natural water and a new insight into the fate and migration of MPs and β-blockers in the environment. Full article

Metoprolol (MTP), a selective beta-1 adrenergic blocker, is commonly administered in the form of succinate or tartrate salts, depending on the pharmaceutical formulation. It is typically prescribed in oral forms as either immediate-release or extended-release tablets. This study describes a chromatographic method using automated sample clean-up and elution via a reversed-phase mechanism. A TurboFlow approach was applied with a Cyclone P column, and the elution was performed isocratically using a mobile phase of water and acetonitrile (0.1% v/v formic acid) within 4.5 min. Quantification of MTP was achieved using triple quadrupole mass spectrometry, with the transition m/z 268.1 → m/z 130.96 for metoprolol, while bisoprolol fumarate, the internal standard, was detected at m/z 326.3 → m/z 116.2. The method was validated according to bioequivalence guidelines. Selectivity was assessed by checking for potential interferences from blank samples or related compounds formed during sample preparation. Precision and accuracy were evaluated both within and between runs, with a maximum coefficient of variation (CV%) of 10.28 and a maximum relative error (ER%) of 5.38. Linearity was demonstrated over the range of 5 ng/L to 1000 ng/L, with a lower limit of quantification at 0.042 ng/L, made possible by injecting larger sample volumes. A matrix effect of 89% was considered acceptable when compared to standard solutions. Plasma concentrations of MTP were monitored in patients administered either 50 mg or 100 mg doses. For the 50 mg dose, plasma levels reached up to 34 μg/L, while the 100 mg dose produced concentrations ranging from 3.56 to 50.81 μg/L. Although the higher dose generally resulted in elevated plasma levels, significant variability was observed. A strong correlation (r = 0.992) was found between the administered dose and plasma concentration, though variations in absorption rates and patient demographics likely contributed to the observed variability. This method provides a reliable analytical approach suitable for pharmacokinetic and clinical studies involving metoprolol. Full article

Metoprolol is a cardioselective beta-blocker drug often used to treat hypertension, but it is considered as a hazardous organic persistent contaminant in wastewater. In this study, a 2.5 L solution of metoprolol (50 mg/L) underwent electro-oxidation in a flow-by reactor using boron-doped diamond electrodes in the batch recirculation mode. The study used multi-objective optimization and multi-criterion decision-making to determine the optimal operating parameters. The response surface methodology and a central composite rotatable design were used with three factors (pH₀: 5–8, I: 2.5–4 A, and Q: 0.8–1.7 L/min) to model the chemical oxygen demand’s (COD’s) removal efficiency and the total organic carbon’s (TOC’s) removal efficiency. The experimental responses were modeled by reduced third- and second-order polynomials with determination coefficients (R²) of 0.9816 and 0.9430. The optimal operating parameters were found to be pH₀ 5, an I value of 3.84 A, and a Q value of 0.8 L/min with an electrolysis time of 7.5 h, resulting in a maximum COD removal efficiency of 60.8% and a TOC removal efficiency of 90.1%. The specific energy consumption was calculated as 9.61 kWh/mg of TOC, with a total operating cost of 0.77 USD/L. In conclusion, this study showed that the electrochemical process is efficient and reliable for treating wastewater containing metoprolol. Full article

Beta-blockers are first-line drugs in the treatment of chronic heart failure (CHF). However, there is no consensus on the specific effects of the beta-blockers of the I-III generation on energy metabolism in CHF. The aim of this study is to conduct a study of beta-blockers of different generations on myocardial energy metabolism in experimental CHF. CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically—new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, Metoprolol—15 mg/kg, Nebivolol −10 mg/kg, Carvedilol 50 mg/kg, and Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined—ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, and NAD-dependent malate dehydrogenase (NAD-MDH) activity. Traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties—Carvedilol and, especially, Nebivalol and Hypertril—improved myocardial energy metabolism. The obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF. Full article