Beta-blocking Drugs Research Articles

Beta-Blocker Interruption or Continuation after Myocardial Infarction

BackgroundThe appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction.MethodsIn a multicenter, open label, randomized, noninferiority trial conducted at 49 sites in France, we randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months. The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). The main secondary end point was the change in quality of life as measured by the European Quality of Life–5 Dimensions questionnaire.ResultsA total of 3698 patients underwent randomization: 1846 to the interruption group and 1852 to the continuation group. The median time between the last myocardial infarction and randomization was 2.9 years (interquartile range, 1.2 to 6.4), and the median follow-up was 3.0 years (interquartile range, 2.0 to 4.0). A primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and in 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P=0.44 for noninferiority). Beta-blocker interruption did not seem to improve the patients’ quality of life.ConclusionsIn patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not found to be noninferior to a strategy of beta-blocker continuation. (Funded by the French Ministry of Health and ACTION Study Group; ABYSS ClinicalTrials.gov number, NCT03498066; EudraCT number, 2017-003903-23.)

Structural and Functional Impact of Adrenoceptor Beta-1 Gene Polymorphism in Patients with Hypertrophic Cardiomyopathy and Response to Beta-Blocker Therapy.

Hypertrophic cardiomyopathy (HCM) is a genetically inherited cardiac disorder with diverse clinical presentations. Adrenergic activity, primarily mediated through beta-adrenoceptors, plays a central role in the clinical course of HCM. Adrenergic stimulation increases cardiac contractility and heart rate through beta-1 adrenoceptor activation. Beta-blocker drugs are recommended as the primary treatment for symptomatic HCM patients to mitigate these effects. This prospective study aimed to investigate the impact of common ADRB-1 gene polymorphisms, specifically serine-glycine at position 49 and arginine-glycine at position 389, on the clinical and structural aspects of HCM. Additionally, the study explored the association between these genetic variations and the response to beta-blocker therapy in HCM patients. A cohort of 147 HCM patients was enrolled, and comprehensive assessments were performed. The findings revealed that the Ser49Gly polymorphism significantly influenced ventricular ectopic beats, with beta-blocker therapy effectively reducing them in Ser49 homozygous patients. Moreover, natriuretic peptide levels decreased, particularly in Ser49 homozygotes, indicating improved cardiac function. Left ventricular outflow obstruction, a hallmark of HCM, was also reduced following beta-blocker treatment in all patient groups. In contrast, the Arg389Gly polymorphism did not significantly impact baseline parameters or beta-blocker response. These results emphasize the role of the Ser49Gly polymorphism in the ADRB-1 gene in shaping the clinical course and response to beta-blocker therapy in HCM patients. This insight may enable a more personalized approach to managing HCM by considering genetic factors in treatment decisions. Further research with larger populations and longer follow-up periods is needed to confirm and expand upon these findings.

Labetalol Ameliorates Experimental Colitis in Rat Possibly Through its Effect on Proinflammatory Mediators and Oxidative Stress.

Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1β, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1β, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.

The role of beta-blocker drugs in critically ill patients: a SIAARTI expert consensus statement

BackgroundThe role of β-blockers in the critically ill has been studied, and data on the protective effects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades. However, consensus and guidelines by scientific societies on the use of β-blockers in critically ill patients are still lacking.The purpose of this document is to support the clinical decision-making process regarding the use of β-blockers in critically ill patients. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient’s care process.MethodsThe Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects underlying the use of β-blockers in critically ill adult patients. The methodology followed by the experts during this process was in line with principles of modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales in the form of informative text. The overall list of statements was subjected to blind votes for consensus.ResultsThe literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with organ dysfunction and increased mortality. Heart rate control thus seems to be critical in the management of the critically ill patient, requiring careful clinical evaluation aimed at both the differential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance. In addition, the use of β-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out. Intravenous application should be the preferred route of administration.Conclusionβ-blockers protective effects in critically ill patients have been repeatedly reported in the literature. Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful differential diagnosis, as all causes of tachycardia should be ruled out and addressed first.

Mimic toxicity of Beta-blocker drugs by structural base descriptors

QSAR study has been carried out on the set of 35 Beta-blocker drugs for the modelling of toxicity (Ld50), using topological indices. The stepwise multilinear regression analysis method is used for modelling and the obtained models are critically discussed and examined by various types of cross validation parameters

Effectiveness of Nitrate and Beta-Blocker Drugs in Patients with Angina Pectoris: A Systematic Literature Review

Angina pectoris is the most common clinical manifestation of myocardial ischemia and often occurs when the heart needs more blood. The main goals of treatment in patients with unstable angina are relief of symptoms, slowing disease progression, and reducing future events, especially myocardial infarction, and death. This study aimed to explore the literature regarding the effectiveness of nitrate and beta-blocker drugs in angina pectoris patients. The literature search process was carried out on various databases (PubMed, Web of Sciences, EMBASE, Cochrane Libraries, and Google Scholar) regarding risk factors and clinical overview of acute kidney injury. The search was performed using the terms: (1) "nitric oxide" OR "beta-blockers" OR "morbidity" OR "mortality" AND (2) "angina pectoris". The literature is limited to clinical studies and published in English. Sublingual nitroglycerin has become the mainstay of treatment for angina pectoris. This drug can be used to relieve acute angina or as a prophylaxis, namely before activities that can trigger angina. Beta-blockers are a type of drug that can be used to relieve angina symptoms and prevent ischemic events through the mechanism of reducing myocardial oxygen demand, reducing heart rate, and myocardial contractility. These drugs work by competitively inhibiting the action of circulating catecholamines at cell membrane beta-adrenergic receptors. In conclusion, nitrate and beta-blocker drugs are the main choices in relieving angina pectoris symptoms.

Microextraction by packed sorbent of some β-blocker drugs with chitosan@mof-199 bio-composite in human saliva, plasma, and urine samples

The current study introduces microextraction by packed sorbent (MEPS) to extract three beta-blocker drugs (propranolol, atenolol, and betaxolol) from biological samples. The separation and detection of the drugs were performed by high performance liquid chromatography followed by UV detection. A green approach was applied for synthesizing chitosan@MOF-199 bio-composite, which was packed into the initial part of a metal spinal (22 gage). The effective parameters on the adsorption and desorption efficiencies, including sample solution pH, eluent flow rate, cycle numbers, type and volume of eluent solvent were evaluated and optimized. Under optimal conditions linear ranges (LRs = 5–600 µg L−1), limits of detection (LODs = 1.5–4.5 µg L−1), and relative standard deviations (RSDs% = 4.7 −5.3% with three replicates and concentration of 100 µg L−1) were obtained. Relative recoveries (RR%) for plasma (77–99%), saliva (81–108%), and urine (80–112%) samples were obtained. In this study, the drug release profile of propranolol in urine was evaluated. The results showed that the highest amount of propranolol is released 4 h after taking the drug. Based on the obtained results, this is an effective, fast, sensitive, reproducible, green, and user-friendly method for beta-blocker drug extraction in biological samples.

Genetic background of sinus node dysfunction requiring permanent pacemaker implantation after atrial fibrillation catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Atrial fibrillation catheter ablation (AFCA) improves sinus node function and may defer a permanent pacemaker (PPM) implantation. We explored the clinical and genetic characteristics of the patients with AF and sinus node dysfunction (SND) who eventually needed PPM implantation after AFCA. Methods Among 2,732 AF patients with genome-wide association study (GWAS, PMRA, Thermofisher scientific, MA, USA) data who underwent the first AFCA, 244 patients (65.0, IQR [59.0, 72.0] years, male 58.2%, paroxysmal AF 79.5%) had underlying SND before AFCA (class I indication for PPM). We retrospectively investigated clinical factors, single-nucleotide polymorphisms (SNPs), and their polygenic risk score (PRS) associated with PPM-AFCA. We defined the cut-off of PRS using the Youden index. Results During median 37.9 (IQR 20.3-77.9) months follow-up, 36 out of 244 patients (16.1%) with underlying SND eventually underwent PPM implantation after AFCA (PPM-AFCA). PPM-AFCA group a had a higher body mass index (p=0.013) and large left atrial (LA) dimension (p=0.006) than their counterpart. Among 44 SNPs related to AF and SND, the rs3922844 (p=0.003) near SCN5A and rs9320841 (p=0.011) and rs1015451 (p=0.046) near CJA1 were significantly associated with PPM-AFCA. The rate of PPM-AFCA implantation was significantly higher in the high PRS group (≥1.175, 25.6%) compared to the low PRS group (&amp;lt;1.175, 9.38%, p=0.002, Log-rank p=0.002). LA dimension (adjusted HR 1.06, 95% CI [1.00-1.13], p=0.044) and PRS (adjusted HR 2.69, 95% CI [1.68-4.31], p&amp;lt;0.001) were associated with a higher risk for PPM-AFCA after adjusting clinical factors including age, sex, AF type, beta blocker, and antiarrhythmic drugs after AFCA. Conclusions In AF patients with SND, 16% with the genetic background of SCN5A and CJA1 or large atrium eventually needed PPM implantation after AFCA.

P149 INTEGRATED CARDIO–RADIOLOGICAL TEAM

Abstract Introduction Cardiovascular diseases are the main cause of mortality: a multidisciplinary approach is essential to fight them successfully. CT coronary angiography and cardiac magnetic resonance are diagnostic tests increasingly used to complement traditional methods. At the "SS Annunziata" hospital in Savigliano (CN) there has already been collaboration between dedicated cardiologists and radiologists for many years: first for CT and then also for MRI. In 2020 the collaboration was formalized, through the drafting of an operating procedure, and the "Integrated multidisciplinary cardio–radiological Team" was officially established. Who is part of the team: Dedicated and identified figures, never occasional, of the Cardiology Department and Radiology Department, whose essential requirements are: a) for cardiologists: advanced competence in echocardiography, general technical knowledge, targeted training b) for radiologists: advanced competence in CT and MRI, mastery of specific sequences and processing techniques, cardiological knowledge. Additional requirements for both figures: certifications and publications. Team activities: 1) Scheduling of exams 2) Discuss the case based on the request and documentation and plan the most suitable technical execution. 3) Monitor for the onset of adverse effects if beta–blocker drugs or stimulant drugs are administered 4) Supervise the execution of the exam: 5) Perform image processing and interpretation: for coronary CT, reconstruction of coronary images in the different modalities, search and quantification of stenoses; for MRI, calculation of volumes and ejection fraction for both ventricles, diameters of the cavities and thicknesses of the walls, search for edema, search and quantification of fibrosis, search for basal perfusion defects and after possible pharmacological stimulation, search for any findings extracardiac. 6) Write and sign the report (radiologist and cardiologist). 7) Contact the patient or the referring doctor by the cardiologist if the findings of the tests performed impose decisive implications of a therapeutic nature. 8) Detect the indicators of set goals Perspectives: The technological advance of cardiac imaging diagnostics, with CT and resonance magnetic, suggests that in the near future these techniques can further improve and open up to new applications that will be the task of the group to evaluate, learn and put into practice.

Role of Cardiac Biomarkers in Non-Small Cell Lung Cancer Patients.

Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (NSCLC) patients, and no biomarkers are currently available in clinical practice. A novel and easy-to-calculate marker is the quantitative analysis of calcium plaque in the coronary, calculated on CT. It is called the Agatston score (or CAD score). At the same time, other potential predictors include cardiac ultrasonography and anamnesis of the patients. Our work aimed to correlate cardiac biomarkers with overall survival (OS) in NSCLC patients. We retrospectively analyzed patients with NSCLC discussed in the Multidisciplinary Tumor Board of our Institute for the present analysis between January 2018 and July 2022. Inclusion criteria were the availability of basal CT imaging of the thorax, cardiac ultrasonography with the calculation of ejection fraction (EF), and complete anamnesis, including assessment of co-pathologies and pharmacological drugs. The clinical data of the patients were retrospectively collected, and the CAD scores was calculated on a CT scan. All of these parameters were correlated with overall survival (OS) with univariate analysis (Kaplan-Meier analysis) and multivariate analysis (Cox regression analysis). Following the above-mentioned inclusion criteria, 173 patients were included in the present analysis. Of those, 120 patients died in the follow-up period (69.6%), and the median overall survival (OS) was 28 months (mean 47.2 months, 95% CI, 36-57 months). In univariate analysis, several parameters that significantly correlated with lower OS were the stage (p < 0.001), the CAD grading (p < 0.001), history of ischemic heart disease (p: 0.034), use of beta blocker drugs (p: 0.036), and cardiac ejection fraction (p: 0.005). In multivariate analysis, the only parameters that remained significant were as follows: CAD score (p: 0.014, OR 1.56, 95% CI: 1.04-1.83), stage (p: 0.016, OR: 1.26, 95% CI: 1.05-1.53), and cardiac ejection fraction (p: 0.011, OR 0.46, 95% CI: 0.25-0.84). Both CAD score and ejection fraction are correlated with survival in NSCLC patients at all stages of the disease. Independently from the treatment choice, a cardiological evaluation is mandatory for patients with NSCLC.

Lysozyme allosteric interactions with β-blocker drugs

Effective and reliable prediction of allosteric molecular interactions involved in protein-ligand systems are essential to understand pharmacological modulation and toxicology processes that are driven by multiple factors covering from the atomistic to cellular level. Even though the interactions taking place within a defined biophysical environment are usually intricate and complex, having a preliminary knowledge of the structural determinant and biochemical function of target enzyme in the physiological or unbound state represent a step forward in the characterization of the forces involved these processes under interaction conditions as induced by drugs. In the present work, we tackle the study of relevant binding interactions between two well-recognized betablocker drugs and the lysozyme biological target from an experimental-computational perspective. In this way, molecular docking, machine learning and perturbation analysis combined with UV–vis and fluorescence measurements will allow us to determine the allosteric regulation and functional dynamics of lysozyme by binding propranolol and acebutolol.

An Update on the Use of Molecularly Imprinted Polymers in Beta-Blocker Drug Analysis as a Selective Separation Method in Biological and Environmental Analysis.

Beta-blockers are antihypertensive drugs and can be abused by athletes in some sport competitions; it is therefore necessary to monitor beta-blocker levels in biological samples. In addition, beta-blocker levels in environmental samples need to be monitored to determine whether there are contaminants from the activities of the pharmaceutical industry. Several extraction methods have been developed to separate beta-blocker drugs in a sample, one of which is molecularly imprinted polymer solid-phase extraction (MIP-SPE). MIPs have some advantages, including good selectivity, high affinity, ease of synthesis, and low cost. This review provides an overview of the polymerization methods for synthesizing MIPs of beta-blocker groups. The methods that are still widely used to synthesize MIPs for beta-blockers are the bulk polymerization method and the precipitation polymerization method. MIPs for beta-blockers still need further development, especially since many types of beta-blockers have not been used as templates in the MIP synthesis process and modification of the MIP sorbent is required, to obtain high throughput analysis.

Propranolol-loaded electrospun nanofibrous wound dressing: From fabrication and characterization to preliminary wound healing evaluation.

Objective(s):The wound healing potential of beta-blocker drugs such as propranolol (PNL) has recently attracted attention. To date, incorporation of PNL into electrospun nanofibrous wound dressing mats has not been tested as a novel topical drug delivery system. Presently, electrospun nanofibrous mats loaded with PNL were fabricated, and their physicochemical properties and wound healing activities were evaluated.Materials and Methods:Polyvinyl alcohol solutions containing 0, 2% or 4% (wt/vol) PNL were electrospun into mats, and the physicochemical properties and PNL release were evaluated. In vitro biocompatibility of selected PNL-loaded mats was tested in human foreskin fibroblasts and wound healing capability was evaluated in mouse skin wounds.Results:The 4% PNL mat had thin fibers (160 nm), convincing porosity (79.5%), and good hydrophilicity (swelling: 89.1%, water contact angle: 42.1°) with little degradability (14.2%). The release of PNL was not in bursts and was best explained by the Korsmeyer–Peppas equation (R2 = 0.96, n = 0.40), suggesting Fickian release. The viability of fibroblasts was 173% on day 5 of incubation with 4% PNL mats, indicating good mat biocompatibility. In vivo treatment for 14 days with 4% PNL mats resulted in wounds with a surface area of only 9% of the original wound area. These wounds had better histopathologic characteristics and were associated with less oxidative stress.Conclusion:The wound dressing fabricated with 4% PNL showed good potential for wound healing because of a favorable drug release profile from the nanofiber scaffold, and can be considered eligible for further clinical research.

Monitoring of pharmaceuticals in aquatic biota (Procambarus clarkii) of the Doñana National Park (Spain)

In this work the presence of different pharmaceuticals at Doñana National Park (Spain) and their main entry sources (input source or entry points) have been stated over the 2011–2016 years period. Twenty-three selected pharmaceuticals (corresponding to eight therapeutic families) were evaluated in crayfish and water samples from Doñana National Park (Spain) (six sampling points selected in order to cover different possible pollution sources into and surrounding the Park). The multiresidue determination was carried out using enzymatic-microwave assisted extraction prior to high performance liquid chromatography mass spectrometry detection. Sulphonamides (sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole); trimethoprim, an antibiotic that is frequently co-administered with sulfamethoxazole; amphenicols (chloramphenicol, florfenicol and thiamphenicol); fluoroquinolones (ciprofloxacin, enrofloxacin, flumequine, danofloxacin, gatifloxacin, norfloxacin, marbofloxacin and grepafloxacin); penicillins (amoxicillin); tetracyclines (chlortetracycline and oxytetracycline); non-steroidal anti-inflammatory drugs (salicylic acid and ibuprofen); beta-blocker drugs (atenolol); and antiepileptics (carbamazepine) were analysed. Ciprofloxacin, ibuprofen, salicylic acid, flumequine, and carbamazepine were detected and/or quantified at some of the selected sampling points. A clear ecotoxicological risk to the ecosystem was demonstrated from the occurrence of ciprofloxacin in samples obtained after the punctual and massive presence of people inside the Park. Furthermore, flumequine and carbamazepine have been detected in Procambarus clarkii specimens in concentrations around 30 ng g−1 and 14 ng g−1, respectively, and their occurrence in the specimens could indicate the persistence of the discharge sources. The main source of pharmaceuticals into the Park might be the livestock farming activities, and the influence of urban wastewaters from surrounding villages does not seem to be very important.

The risk of worsening of myasthenia by cardiovascular medication as reflected by reporting frequency.

Some groups of cardiovascular drugs (beta-blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided. From the World Health Organization pharmacovigilance database, we retrieved total and myasthenia-related counts of adverse drug reactions for various groups of drugs used in cardiovascular disease and drugs with related mechanism of action used in other indications. We calculated the reporting odds ratio as a measure of a disproportional fraction of myasthenia-related events among all events. A 95% confidence interval of reporting odds ratio (ROR) >1 was taken as an indication for a higher risk. Because our approach involves a considerable number of tests, this situation is referred to as a signal that requires additional confirmation. A signal for an increased risk was noted for tizanidine, for alpha-blocking drugs, for beta-blocking drugs, and for Ca antagonists. ROR indicated a lower-than-average risk for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins. Angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, and diuretics seem to be safe in antihypertensive therapy. Surprisingly, and yet requiring confirmation by case reports, alpha receptor-blocking drugs seem to carry a risk of myasthenia worsening. Amiodarone seems to be a safe alternative in antiarrhythmic therapy in patients with myasthenia.

Do topical antiglaucoma drugs affect the cornea?

To investigate effects of beta blocker (BB; timolol or betaxolol), latanoprost, and latanoprost-timolol combination (LTC) drugs on corneal endothelial cell density (ECD) and central corneal thickness (CCT) in primary open-angle glaucoma (POAG) patients. Sixty-one patients in BB group, 64 patients in latanoprost group, 59 patients in LTC group, and 58 healthy cases in control group were included. Intraocular pressures (IOP), ECDs, and CCTs of groups were recorded at initial (pre-treatment) period, first and third years after treatment, and comparisons were done. In groups, changes of ECDs according to time were not significant (p > 0.05). In BB and control groups, changes of CCTs according to time were not significant (p > 0.05). In latanoprost and LTC groups, CCTs in both first and third years were significantly thinner than initial CCTs (p = 0.039 for latanoprost, p = 0.041 for LTC at first year; p = 0.018 for latanoprost, p = 0.032 for LTC at third year). In latanoprost and LTC groups, CCTs of patients using drugs for 1 year were similar to those of patients using drugs for 3 years (p > 0.05). In our study, uses of BB, latanoprost or LTC did not affect ECD. BB drugs had no effect on CCT. Although latanoprost and LTC appeared to reduce CCT at 3-year follow-up from the statistical point of view, this 8-10 μm difference in CCT was not clinically significant.

Partitioning and Spatial Distribution of Drugs in Ocular Surface Tissues.

Ocular drug absorption after eye drop instillation has been widely studied, but partitioning phenomena and spatial drug distribution are poorly understood. We investigated partitioning of seven beta-blocking drugs in corneal epithelium, corneal stroma, including endothelium and conjunctiva, using isolated porcine tissues and cultured human corneal epithelial cells. The chosen beta-blocking drugs had a wide range (−1.76–0.79) of n-octanol/buffer solution distribution coefficients at pH 7.4 (Log D7.4). In addition, the ocular surface distribution of three beta-blocking drugs was determined by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) after their simultaneous application in an eye drop to the rabbits in vivo. Studies with isolated porcine corneas revealed that the distribution coefficient (Kp) between the corneal epithelium and donor solution showed a positive relationship and good correlation with Log D7.4 and about a 50-fold range of Kp values (0.1–5). On the contrary, Kp between corneal stroma and epithelium showed an inverse (negative) relationship and correlation with Log D7.4 based on a seven-fold range of Kp values. In vitro corneal cell uptake showed a high correlation with the ex vivo corneal epithelium/donor Kp values. Partitioning of the drugs into the porcine conjunctiva also showed a positive relationship with lipophilicity, but the range of Kp values was less than with the corneal epithelium. MALDI-IMS allowed simultaneous detection of three compounds in the cornea, showed data in line with other experiments, and revealed uneven spatial drug distribution in the cornea. Our data indicate the importance of lipophilicity in defining the corneal pharmacokinetics and the Kp values are a useful building block in the kinetic simulation models for topical ocular drug administration.

Fast fabric phase sorptive extraction of selected β-blockers from human serum and urine followed by UHPLC-ESI-MS/MS analysis

A fast fabric phase sorptive extraction method is presented herein for the rapid isolation of selected beta-blocker drugs from human serum and urine. Among many high efficiency sol-gel sorbent coated FPSE membranes, sol-gel CW20 M coated FPSE membrane was identified as the best FPSE membrane for the target beta-blocker drugs possessing logP values ranging from 0.1 (highly polar) to 3.1 (moderately polar). Due to the engineered affinity towards the analytes via complementary intermolecular interactions and high mass transfer rate of the analytes from the bulk sample solution to the FPSE membrane, the extraction is accomplished in relatively short time (15 min) while its high permeability permits the direct extraction of biological samples without any other pretreatment. The advantages of the fabricated extraction membrane were exploited for the determination of six beta-blockers (namely atenolol, nadolol, metoprolol, oxprenolol, labetalol and propranolol) in biological matrices in combination with UHPLC-ESI-MS/MS. Important parameters including extraction time, sample volume, sorbent size, elution solvent, etc. affecting the performance of the extraction were systematically investigated. The linearity of the method was evaluated in the range of 50–5000 ng mL−1 by constructing weighted (1/X) matrix-matched calibration curves. The intra-day and inter-day trueness were ranged between – 17.2 to 13.3% and – 10.8 to 12.6%, respectively. The intra-day and inter-day precision were less than 11.5 and 14.5 %, respectively. The proposed analytical scheme was successfully applied to the determination of the target drugs in human serum and urine.

Diagnostic and Therapeutic Resources for Risk Stratification of Patients With Acute Coronary Syndrome

Acute coronary syndrome (ACS) results from acute obstruction of a coronary artery which is responsible for a high mortality rate worldwide. The consequences depend on the degree and location of the obstruction and vary from unstable angina to non-ST segment elevation myocardial infarction (NSTEMI), ST-segment elevation myocardial infarction, and sudden cardiac death. The symptoms are similar in each of these syndromes (except for sudden death), involving chest discomfort with or without dyspnea, nausea, and diaphoresis. The diagnosis is possible; thanks to the electrocardiogram that is essential and the existence or absence of serological markers. In addition to these initial resources, other diagnostic methods are noteworthy, such as stress electrocardiogram, echocardiography, nuclear cardiology, computed tomography angiography, and exercise test. Other necessary measures are the stratification of the identified cases according to the degree of risk, availability of a coronary intensive care unit, and the establishment of the opportune treatment that consists of oxygen therapy, analgesia, sedation, antiplatelet, anticoagulants, nitrates, beta-blockers drugs, reperfusion of emergency with fibrinolytic drugs, percutaneous intervention or, occasionally, myocardial revascularization surgery to provide the recovery and consequently a better quality of life for the patient. This brief review aims to discuss the available diagnostic and therapeutic resources and the appropriate risk stratification for adequate care for the victims of acute coronary heart disease promptly in a hospital setting.

Studi Penggunaan Obat Golongan Beta-Blocker Pada Pasien Rawat Inap Rumah Sakit Ansari Saleh Banjarmasin

Beta-blockers have a role in cardiovascular and non-cardiovascular therapy. Many beta-blockers are now available and in general they are all equally effective. There are, however, differences between them, which may affect choice in treating particular diseases or individual patients. Research related to the profile of beta-blocker drug use in cardiovascular and non-cardiovascular therapy is still limited. This study aims to describe the use of beta-blockers in inpatients at Ansari Saleh Hospital, Banjarmasin. This retrospective descriptive study was conducted from April to May 2019 at the Anshari Saleh Hospital, Banjarmasin. The beta-blocker drugs used were bisoprolol and propranolol which were administered in cardiovascular medications such as angina (3.7%); arrhythmia (3%); Congestive Heart Failure (20%); hypertension (3%); myocardial infarction (54.8%); non hemorrhagic stroke (9.6%); and non-cardiovascular including hepatic cirrhosis (1.5%); hyperthyroidism (4.4%). The bisoprolol dosage used by inpatients at Ansari Saleh Hospital starts from 1.25 to 5 mg per day. Myocardial infarction and non-hemorrhagic stroke patients received bisoprolol dose uptitration. The propranolol dosage is 20-30 mg per day. In cardiovascular patients, bisoprolol is a drug that is often given to patients with comorbids than propranolol.&#x0D; Keywords: Beta-blockers, cardiovascular, non-cardiovascular, therapy