Channel Blocking Drug Research Articles

Verapamil-Loaded Cubosomes for Enhancing Intranasal Drug Delivery: Development, Characterization, Ex Vivo Permeation, and Brain Biodistribution Studies

Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high Er value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution.Graphical

Green and efficient preconcentration of calcium channel blocker drugs in water using effervescence powder in syringe-assisted deep eutectic solvent dispersive liquid-liquid microextraction

Efficient preconcentration techniques are crucial for the analysis of calcium channel blocker drugs such as amlodipine and nifedipine, commonly used for hypertension and heart diseases. This study optimized the preconcentration conditions using CO2 effervescence powder assisted deep eutectic solvent dispersive liquid-liquid microextraction (EP-DLLME). A central composite design with 30 experiments was employed to determine the effects of extraction solvent volume, effervescence powder mass, water sample volume, and pH water. The optimized conditions for EP-DLLME were determined as follows: 500-μL of extraction solvent, 25-mL of water sample, 5 mg of effervescence powder, and pH 8. High-performance liquid chromatography (HPLC) coupled with a diode array detector was utilized for subsequent analysis. The method exhibited good linearity (r2 = 0.996) and low limits of detection and quantification: 1.73 ng/mL and 5.76 ng/mL for amlodipine, and 0.37 ng/mL and 1.23 ng/mL for nifedipine, respectively. The extraction efficiency, evaluated at three concentration levels, resulted in recoveries ranging from 73 % to 98 %. Repeatability analysis showed satisfactory intra-day and inter-day relative standard deviation values: 3.65 % to 8.38 % for amlodipine and 1.9 % to 10.11 % for nifedipine in the intra-day analysis, and 2.46 % to 9.07 % for amlodipine and 2.92 % to 10.7 % for nifedipine in the inter-day analysis. Furthermore, the EP-DLLME method demonstrated environmental sustainability, achieving a total AGREEnness score of 0.68, emphasizing its environmentally friendly nature.

Twelve-Lead ECG, Holter Monitoring Parameters, and Genetic Testing in Brugada Syndrome: Insights from Analysis of Multigenerational Family with a History of Sudden Cardiac Arrest during Physical Activity.

Brugada syndrome (BrS) is an arrhythmogenic disorder increasing the risk of syncopal episodes and sudden cardiac death. BrS usually runs through families with reduced penetrance and variable expression. We analyzed the multigenerational family of a patient who died after sudden cardiac arrest with post-mortem diagnosis of BrS. We analyzed clinical history, comprehensive arrhythmic risk, genetic findings, and additional tests, including electrocardiogram (ECG), detailed 24-hour Holter ECG results, and standard echocardiography findings, and followed up the patients in the ambulatory clinic. We analyzed a pedigree of 33 members of four generations of the family (19 male and 14 female patients). In this family, we identified 7 patients with BrS (median Modified Shanghai Score and Sieira model: 4.5 (4-6) and 1 (0-4) points, respectively), including both parents of the deceased patient, and 8 relatives with negative sodium channel blocker drug challenge test. Genetic testing revealed a novel mutation in sodium voltage-gated channel alpha subunit 5 (SCN5A) c.941A>G, (p.Tyr314Cys) inherited from the father of the proband. Patients with BrS were characterized by longer P-wave duration (120 (102-155) vs. 92.5 (88-110) ms, p = 0.013) and longer PR intervals (211.3 ±26.3 vs. 161.6 ± 18.9 ms, p = 0.001), along with more frequent positive aVR sign, but did not differ in terms of QRS duration or T-wave characteristics in resting ECGs. BrS patients were characterized by lower mean, minimal, and maximal (for all p ≤ 0.01) heart rates obtained from Holter ECG monitoring, while there was no difference in arrhythmias among investigated patients. Moreover, visual diurnal variability of ST segment changes and fragmented QRS complexes were observed in patients with BrS in Holter ECG monitoring. There were no major arrhythmic events during median follow-up of 68.7 months of alive BrS patients. These results suggest ECG features which may be associated with a diagnosis of BrS and indicate a novel SCN5A variant in BrS patients. Twelve-lead Holter ECG monitoring, with modified precordial leads placement, may be useful in BrS diagnostics and risk stratification in personalized medicine.

Prevalence and Severity of Amlodipine-induced Gingival Enlargement.

The administration of several classes of drugs; anticonvulsants, immunosuppressants, and calcium channel blockers can cause gingival enlargement. The aim of the present study was to evaluate the frequency and severity of gingival enlargement in patients taking calcium channel blocker drug amlodipine. This descriptive cross-sectional study was conducted on 250 patients who visited the dental hospital at Nepal Medical College between November 2021 to April 2022. Using the Bokenkamp and Bornhorst Index, the patients who had been on amlodipine for at least three months were examined for gingival enlargement. Along with gingival and plaque index, medication dosage and duration were also assessed. The prevalence of gingival enlargement was 37%. Grade 1 gingival enlargement was present in 18% while grade 3 was seen in only 2%. Both individuals taking amlodipine alone and in combination with other antihypertensive drugs showed the same level of gingival enlargement. The dose and duration of amlodipine ingestion showed a significant correlation with the enlargement. The gingival and plaque index also showed a strong correlation with overgrowth. The physicians prescribing amlodipine should well inform the patients about the potential side effects. In such cases, the maintenance of oral hygiene should be prioritized from the beginning. In severe cases, substitution of the drugs followed by oral therapeutic measures should be considered for complete regression.

Cationic nanocapsule suspension as an alternative to the sublingual delivery of nifedipine

Nifedipine (NIFE) is a calcium channel blocker drug used to treat cardiovascular diseases, angina, and hypertension. However, NIFE is photolabile, has a short biological half-life, low aqueous solubility, and undergoes an intense first-pass effect, compromising its oral bioavailability. Thus, this study aimed to develop NIFE-loaded nanocapsules for sublingual administration. Nanocapsule suspensions of Eudragit® RS100 and medium chain triglycerides containing NIFE were prepared by the interfacial deposition of preformed polymer technique. The developed formulations showed particle size around 170 nm, polydispersity index below 0.2, positive zeta potential, and acid pH. The NIFE content was 0.98 ± 0.03 mg/mL, and the encapsulation efficiency was 99.9%. The natural light photodegradation experiment showed that the nanocapsules were able to provide NIFE photoprotection. The nanocapsules reduced the cytotoxicity of NIFE and showed no genotoxic effects in the Allium cepa model. Through the HET-CAM test, the formulations were classified as non-irritating. The developed nanocapsule suspension demonstrated a controlled release of NIFE and mucoadhesive potential. The in vitro permeation assay showed that the nanocapsules favored the NIFE permeation to the receptor compartment. In addition, the nanocapsules provided greater drug retention in the mucosa. Thus, the development of polymeric nanocapsule suspensions showed that this system could be a promising platform for NIFE sublingual administration.

Sodium bicarbonate reverts electrophysiologic cardiotoxicity of ropivacaine faster than lipid emulsions in a porcine model.

Ropivacaine has been described as a safer local anaesthetic (LA); however, serious cardiotoxic accidents have been reported. Intravenous-lipid-emulsion (ILE) therapy during LA intoxication seems to act as an antidote. Sodium bicarbonate is the standard treatment for sodium channel blocker drug toxicity. We compared both antidotes on the reversion of electrophysiologic toxicity induced by ropivacaine. Ropivacaine 5mg kg-1 was administered in 24 pigs, and 3min later, the animals received ILE: 1.5ml kg-1 + 0.25 ml kg-1 min-1 (ILE group); sodium bicarbonate: 2mEq kg-1 + 1mEq kg-1 h-1 (NaHCO3 group); saline solution (CTL group). Electrophysiological parameters were evaluated for 30 min. The area under the curve (AUC) for the first 5 or 30 min was compared between groups. Ropivacaine induced a lengthening of the PR interval by 17% (P= 0.0001), His-ventricle-interval by 58% (P= 0.001), sinus QRS complex by 56% (P= 0.0001), paced QRS at 150 bpm by 257% (P= 0.0001), and at 120 bpm by 143% (P= 0.0001) in all groups. At 5min after treatment, sinus QRS in the NaHCO3 group was shorter than that in the CTL group (AUCQRS5 , P= 0.003) or ILE group (AUCQRS5 , P= 0.045). During the first minute, seven of the animals in the NaHCO3 group vs. two in the ILE or 0 in the CTL group recovered more than 30% of the sinus QRS previously lengthened by ropivacaine (P= 0.003). Sodium bicarbonate reversed the electrophysiological toxicity of ropivacaine faster than ILE and control groups.

Screening, diagnosis and follow-up of Brugada syndrome in children: aDutch expert consensus statement.

Brugada syndrome (BrS) is a rare inherited arrhythmia syndrome. Affected children may experience life-threatening symptoms, mainly during fever. The percentage of SCN5A variant carriers in children is higher than in adults. Current diagnostic and follow-up policies for children with (a family history of) BrS vary between centres. Here, we present a consensus statement based on the current literature and expert opinions to standardise the approach for all children with BrS and those from BrS families in the Netherlands. In summary, BrS is diagnosed in patients with a spontaneous type 1 electrocardiogram (ECG) pattern or with a Shanghai score ≥ 3.5 including ≥ 1 ECG finding. A sodium channel-blocking drug challenge test should only be performed after puberty with a few exceptions. A fever ECG is indicated in children with suspected BrS, in children with a first-degree family member with definite or possible BrS according to the Shanghai criteria with a SCN5A variant and in paediatric SCN5A variant carriers. In-hospital rhythm monitoring during fever is indicated in patients with an existing type 1 ECG pattern and in those who develop such a pattern. Genetic testing should be restricted to SCN5A. Children with BrS and children who carry an SCN5A variant should avoid medication listed at www.brugadadrugs.org and fever should be suppressed. Ventricular arrhythmias or electrical storms should be treated with isoproterenol infusion.Supplementary InformationThe online version of this article (10.1007/s12471-022-01723-6) contains supplementary material, which is available to authorized users.

Experimental, Molecular Docking and Molecular Dynamics Investigation on Newly Synthesized Diethyl 4-(Anthracen-9-yl)-2,6-Dimethyl-1,4-Dihydropyridine-3,5-Dicarboxylate

The novel compound diethyl 4-(anthracen-9-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (DHPA) was synthesized via the Hantzsch method. The synthesized compound was studied through FT-IR, FT-Raman, UV-Vis and NMR studies were compared with Density Functional Theory (DFT) calculations using the B3LYP exchange-correlation functional to evaluate the synthesized compound. Analyzing the molecular structure of the compound provides more biological information that aids in drug design. Quantum chemical calculations using the DFT method, such as molecular geometry optimization, vibrational assignments, frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) map, natural bond orbitals (NBO), global reactive descriptors, and local reactive descriptors, were performed to analyze the structural characteristics and biological properties of the compound. Finally, molecular docking and molecular dynamics were used to determine the binding interaction and stability of the compound in the docked site. The results from simulation studies suggest that DHPA might be an alternative calcium channel blocker drug.

An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic pro-arrhythmia mechanisms.

Before advancing to clinical trials, new drugs are screened for their pro-arrhythmic potential using a method that is overly conservative and provides limited mechanistic insight. The shortcomings of this approach can lead to the mis-classification of beneficial drugs as pro-arrhythmic. An in silico-in vitro pipeline was developed to circumvent these shortcomings. A computational human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model was used as part of a genetic algorithm to design experiments, specifically electrophysiological voltage clamp (VC) protocols, to identify which of several cardiac ion channels were blocked during in vitro drug studies. Such VC data, along with dynamically clamped action potentials (AP), were acquired from iPSC-CMs before and after treatment with a control solution or a low- (verapamil), intermediate- (cisapride or quinine) or high-risk (quinidine) drug. Significant AP prolongation (a pro-arrhythmia marker) was seen in response to quinidine and quinine. The VC protocol identified block of IKr (a source of arrhythmias) by all strong IKr blockers, including cisapride, quinidine and quinine. The protocol also detected block of ICaL by verapamil and Ito by quinidine. Further demonstrating the power of the approach, the VC data uncovered a previously unidentified If block by quinine, which was confirmed with experiments using a HEK-293 expression system and automated patch-clamp. We developed an in silico-in vitro pipeline that simultaneously identifies pro-arrhythmia risk and mechanism of ion channel-blocking drugs. The approach offers a new tool for evaluating cardiotoxicity during preclinical drug screening.

Enlarged Pericarotid Lymph Nodes Suggest Recent Ischemic Symptoms in Patients with Carotid Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease closely associated with immunological activity. Lymph nodes (LNs) are essential secondary lymphoid organs, in which complex immune responses occur. Enlarged LNs are commonly observed around inflamed tissues or tumors; however, their role in atherosclerosis is not well understood. We hypothesized that enlarged pericarotid LNs would be present in symptomatic patients with carotid atherosclerosis. Therefore, we recorded the size of LNs around the carotid artery during surgery in patients undergoing carotid endarterectomy (CEA) for carotid atherosclerotic stenosis. Patients were stratified by enlarged LNs, defined as a diameter ≥ 10mm in the transverse diameters. Demographic and clinical data of participants were measured and analyzed. Hematoxylin and eosin (H&E), Sirius red, DAB-enhanced Perls’ Prussian blue, alizarin red, and immunohistochemistry (IHC) staining were performed for composition identification of plaques or LNs. Symptomatic patients were defined as those presenting with an ipsilateral cerebral ischemic event. Compared with patients with non-enlarged LNs, patients with enlarged LNs were more likely to be symptomatic (22/32, 68.8% versus 9/40, 22.5%, P < 0.001) and use calcium channel blocker drugs (17/32, 53.1% versus 10/40, 25%, P=0.014). In addition, they showed lower body mass index (mean ± SD: 24.00 ± 2.66 versus 25.34 ± 2.56 kg/m2, P=0.034), lower weight (median [interquartile range]: 64 [60.00-76.00] versus 72.5 [65.00-77.50] Kg, P = 0.046) and higher diastolic blood pressure (mean ± SD: 78.94 ± 9.30 versus 73.93 ± 8.84 mmHg, P = 0.022). The plague from patients with enlarged LNs exhibited a lower relative percentage of fibrous tissue (29.49 ± 10.73% versus 34.62 ± 10.33%, P = 0.041). The enlarged LNs remained oval-shaped by visual inspection. Compared to non-enlarged LNs, the predominant changes in enlarged LNs were atrophic lymphatic sinuses and dilated LNs parenchyma. Enlarged LNs contained more germinal centers and lymphocytes. In conclusion, symptomatic patients with carotid atherosclerosis have enlarged pericarotid LNs. The current study supports the conclusion that enlarged LNs with an activated and enhanced adaptive immune response may indicate plaque instability. Pericarotid LNs will be a promising marker of plaque stability and may be a potential therapeutic target in patients with carotid atherosclerosis.

The clinical and bioinformatics analysis for the role of antihypertension drugs on mortality among patients with hypertension hospitalized with COVID-19.

Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)‐19 infection. Patients with hypertension may receive both anti‐COVID‐19 and antihypertension therapies when infected with COVID‐19. However, it is not clear how different classes of anti‐hypertension drugs impact the outcome of COVID‐19 treatment. Herein, we explore the association between the inpatient use of different classes of anti‐hypertension drugs and mortality among patients with hypertension hospitalized with COVID‐19. We totally collected data from 278 patients with hypertension diagnosed with COVID‐19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single‐cell RNA‐sequencing (RNA‐Seq) analysis of treatment‐related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin‐converting enzyme inhibitor/β‐block/diuretic drugs did not affect the mortality caused by COVID‐19. Based on the analysis of four public data sets of single‐cell RNA‐Seq on COVID‐19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID‐19‐related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID‐19‐related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID‐19.

Medication errors with influencing factors of polypharmacy among elderly patients using Calcium Chanel Blockers.

Background: Geriatrics refers to age-related health changes and consequently causes complications in polypharmacy, generalizing prescribing patterns. The study aimed to investigate the pervasiveness of medication inaccuracies along with drug interactions. Methodology: Out of 450 prescriptions only 210 were selected that contained Calcium Channel Blocker (CCB) and other drugs. Drug-drug interactions were articulated by Micromedex 2.0, and the harm score was determined by National Coordinating Council for Medication Error Reporting and Prevention. Results: The outcomes revealed that 645 medication errors were identified and multiple errors were present in a single prescription. The most frequent error was unstated patient's weight (98.6%) proceeds from drug-drug interactions (66.7%). According to the harm score, 36.66% of prescriptions were placed in category D, there was a statistically significant association between the drug-drug interaction and the number of prescribed drugs (p&lt;0.0001). Conclusion: The prime solution is that the physicians should be facilitated withal trainings about drug interactions and prescription writing skills according to WHO guidelines or other recognized standards.

Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias.

Cardiomyopathies are associated with arrhythmias and cardiac ion channel downregulation. This downregulation is arrhythmogenic. Paradoxically, antiarrhythmic therapies are based on ion channel-blocking drugs that further downregulate these channels and exhibit proarrhythmic risk. Recent studies have shown that inhibition of the protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) prevents select cardiac ion channel downregulation and plays a protective role against arrhythmias. Prevention of ion channel downregulation represents as a novel therapeutic strategy to treat arrhythmias in myocardial infarction and heart failure.

Electromechanical integrated recording of single cardiomyocyte in situ by multimodal microelectrode biosensing system

The development of new drugs is a lengthy process, while the observation of serious side effects, such as cardiotoxicity, can result in the drug to be withdrawn even after development, leading to heavy burden on human health and social economy. To assess the drug cardiotoxicity, the electrical and mechanical properties of cardiomyocytes are increasingly being used to investigate the mechanisms and potential toxicity of drugs. Conventional non-invasive and label-free recording strategies are not well suited to record the integrated electromechanical signals from the single cell in a high-throughput manner, whereas label-based recordings strategies suffer from phototoxicity and drug side effects, precluding their long-time detection. In this study, we established a new multimodal microelectrode biosensing system to achieve the simultaneous and dynamic interrogation of electromechanical signals from multisite single cardiomyocytes. This multimodal device can detect subtle changes in the electromechanical signals induced by ion channel drugs during the excitation-contraction coupling of cardiomyocytes. The use of electromechanical integrated single cell signals for drug assessment was compared with commercial drug assays, and our multimodal microelectrode biosensing system can afford record electromechanical integrated signals as well as efficiently identify the effects of ion channel-blocking drugs on the electrical and mechanical properties of cardiomyocytes. Our multimodal microelectrode biosensing system is a potential valuable platform in the fields of cardiology and pharmacology.

Arrhythmic Phenotypes Are a Defining Feature of Dilated Cardiomyopathy-Associated SCN5A Variants: A Systematic Review.

Variants in the SCN5A gene, that encodes the cardiac sodium channel, Nav1.5, are associated with a highly arrhythmogenic form of dilated cardiomyopathy (DCM). Our aim was to review the phenotypes, natural history, functional effects, and treatment outcomes of DCM-associated rare SCN5A variants. A systematic review of reported DCM-associated rare SCN5A variants was undertaken using PubMed and Embase. Eighteen SCN5A rare variants in 29 families with DCM (173 affected individuals) were identified. Eleven variants had undergone experimental evaluation, with 7 of these resulting in increased sustained current flow during the action potential (eg, increased window current) and at resting membrane potentials (eg, creation of a new gating pore current). These variants were located in transmembrane voltage-sensing domains and had a consistent phenotype characterized by frequent multifocal narrow and broad complex ventricular premature beats (VPB; 72% of affected relatives), ventricular arrhythmias (33%), atrial arrhythmias (32%), sudden cardiac death (13%), and DCM (56%). This VPB-predominant phenotype was not seen with 1 variant that increased late sodium current, or with variants that reduced peak current density or had mixed effects. In the latter groups, affected individuals mainly showed sinus node dysfunction, conduction defects, and atrial arrhythmias, with infrequent VPB and ventricular arrhythmias. DCM did not occur in the absence of arrhythmias for any variant. Twelve studies (23 total patients) reported treatment success in the VPB-predominant cardiomyopathy using sodium channel-blocking drug therapy. SCN5A variants can present with a diverse spectrum of primary arrhythmic features. A majority of DCM-associated variants cause a multifocal VPB-predominant cardiomyopathy that is reversible with sodium channel blocking drug therapy. Early recognition of the distinctive phenotype and prompt genetic testing to identify variant carriers are needed. Our findings have implications for interpretation and management of SCN5A variants found in DCM patients with and without arrhythmias.

Incidence and evolution of foreign body impaction in the upper gastrointestinal tract and its relationship with eosionophilic oesophagitis

BackgroundForeign body impaction is a frequent indication of urgent endoscopy. One of the reasons for impaction is eosinophilic oesophagitis (EE). To analyze characteristics of oesophageal foreign body impactions and their relationship with eosinophilic oesophagitis. MethodsIn this retrospective study, urgent endoscopies in a tertiary care centre were analyzed. We included all urgent endoscopies due to bolus and foreign body impactions performed between September 1st 2018 and September 1st 2020. We reviewed clinical data of all patients who were diagnosed with EE and compared it to impactions that were due to other motives. The mean follow-up time was 18.7 months. Results693 urgent endoscopy procedures were performed. 239 (34%) of these were due to foreign body ingestion. Mean age of the patients was 63 years old and 135 (63%) were men. EE was diagnosed in 36 (17%) patients. The factors associated with EE were age, to be younger than 50 years (OR, 7.3; 95% CI, 1.1–48.4; p=0.04), asthma/rhinitis/atopic dermatitis (OR, 8.9; 95% CI, 2.3–35.3; p=0.002), findings in the endoscopy as trachealization (OR, 9.7; 95% CI, 1.3–70.9; p=0.03) and psychotropic/calcium channel blocker drugs (OR, 0.09; 95% CI, 0.009–0.9; p=0.04). 15 (7%) patients died. In 6 of them death was impaction-related. None patients with EE died. ConclusionsForeign body impaction in the upper gastrointestinal tract due to EE is a frequent cause of urgent endoscopy. Being under 50 years of age, having asthma/rhinitis/atopic dermatitis, trachealization on the oesophagus and not taking psychotropic/calcium channel blocker drugs are factors associated with the diagnosis of EE. Mortality in the follow-up of patients without EE is important.

New Charge Transfer Complexes of K+-Channel-Blocker Drug (Amifampridine; AMFP) for Sensitive Detection; Solution Investigations and DFT Studies.

UV–Vis spectroscopy was used to investigate two new charge transfer (CT) complexes formed between the K+-channel-blocker amifampridine (AMFP) drug and the two π-acceptors 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tetracyanoethylene (TCNE) in different solvents. The molecular composition of the new CT complexes was estimated using the continuous variations method and found to be 1:1 for both complexes. The formed CT complexes’ electronic spectra data were further employed for calculating the formation constants (KCT), molar extinction coefficients (εCT), and physical parameters at various temperatures, and the results demonstrated the high stability of both complexes. In addition, sensitive spectrophotometric methods for quantifying AMFP in its pure form were proposed and statistically validated. Furthermore, DFT calculations were used to predict the molecular structures of AMFP–DDQ and AMFP–TCNE complexes in CHCl3. TD-DFT calculations were also used to predict the electronic spectra of both complexes. A CT-based transition band (exp. 399 and 417 nm) for the AMFP–TCNE complex was calculated at 411.5 nm (f = 0.105, HOMO-1 → LUMO). The two absorption bands at 459 nm (calc. 426.9 nm, f = 0.054) and 584 nm (calc. 628.1 nm, f = 0.111) of the AMFP–DDQ complex were theoretically assigned to HOMO-1 → LUMO and HOMO → LUMO excitations, respectively.

The Evaluation of Fasting Plasma Glucose (FPG) Levels in Hypertensive Patients Using Calcium Channel Blocker (CCB) Drugs Class in Undata Regional Hospital

Background: Hypertension plays a major role in the development of heart disease which is one of the most leading causes of death worldwide. Antihypertensives must be selected carefully to avoid affecting metabolic parameters. A risky case involving the increase of plasma glucose levels using Calcium Channel Blocker (CCB) antihypertensive, amlodipine, has been reported. Objectives: This study aims to examine the effects of CCB treatments on blood glucose levels in hypertensive patients at the Undata District General Hospital of Central Sulawesi Province. Material and Methods: This study used a cross-sectional design with a prospective approach. The instruments &amp; materials used in this study are Accu-Chek Performa glucometer along with the patient's blood sample material. The research subjects were 31 patients who met the inclusion criteria; patients had been treated with CCB therapy for 3 months, patients were not diagnosed with diabetes mellitus, andpatients did not use drugs that might affect the blood glucose levels. Results: The results showed an average value of fasting plasma glucose (FPG) levels of hypertension patients using CCB class showed an increase from baseline of 124,619 mg/dL to 141,612 mg/dL with a difference of 16,993 mg/dL. Statistical analysis conducted also obtained a significance value of p 0,000 which indicates that the use of amlodipine can significantly increase fasting patients' plasma glucose levels. Conclusions: If observed clinically, the increasing in fasting plasma glucose values ​​falls into the category of mild to moderate hyperglycemic.

Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread.

COVID-19 is caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2). The virus is responsible for an ongoing pandemic and concomitant public health crisis around the world. While vaccine development is proving to be highly successful, parallel drug development approaches are also critical in the response to SARS-CoV-2 and other emerging viruses. Coronaviruses require Ca2+ ions for host cell entry, and we have previously shown that Ca2+ modulates the interaction of the viral fusion peptide with host cell membranes. In an attempt to accelerate drug repurposing, we tested a panel of L-type calcium channel blocker (CCB) drugs currently developed for other conditions to determine whether they would inhibit SARS-CoV-2 infection in cell culture. All the CCBs tested showed varying degrees of inhibition, with felodipine and nifedipine strongly limiting SARS-CoV-2 entry and infection in epithelial lung cells at concentrations where cell toxicity was minimal. Further studies with pseudotyped particles displaying the SARS-CoV-2 spike protein suggested that inhibition occurs at the level of virus entry. Overall, our data suggest that certain CCBs have the potential to treat SARS-CoV-2 infections and are worthy of further examination for possible treatment of COVID-19.

Inherited Arrhythmia Syndromes.

Inherited Arrhythmia Syndromes.