Search Results (319)

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

We used molecular docking as a computational tool to predict the binding affinities and interactions of quercetin 3-O-malonylglucoside (Q3MG) with vascular target proteins. First, the proteins 1M9M (human endothelial nitric oxide synthase; eNOS) and 6ND0 (human large-conductance voltage- and calcium-activated K⁺ channels; BK_Ca) were downloaded from the Protein Data Bank and submitted to molecular docking studies, revealing Q3MG binding affinities for both proteins. The vascular effect of Q3MG was investigated in the perfused mesenteric vascular beds (MVBs) of spontaneously hypertensive rats. In preparations with functional endothelium, Q3MG dose-dependently reduced the perfusion pressure in MVBs. Removal of the endothelium or inhibition of the nitric oxide synthase enzyme by L-NAME blocked the vasodilation induced by Q3MG. Perfusion with a physiological solution containing high KCl or the use of a non-selective blocker of K⁺ channels, as well as perfusion with iberiotoxin, completely abolished the vasodilatory effects of Q3MG. The data obtained suggest that the vascular effects of Q3MG involve the activation of the NO/cGMP pathway followed by the opening of BK_Ca. Full article

Background: Falls are a major cause of morbidity and mortality among older adults and are influenced by comorbidities and polypharmacy. Cardiovascular diseases (CVDs) and their associated treatments are particularly prevalent in this population and may contribute to fall risk. Objectives: The objectives of this study were to examine the association between cardiovascular pharmacotherapy and fall risk in older adults and to identify potential preventive strategies. Methods: This observational case–control study was conducted between June and December 2024 and included 200 participants aged over 55 years who provided informed consent. Participants were assessed using the Downton Fall Risk Index and divided into two equal groups, with those at high risk of falling and controls. All participants underwent a comprehensive geriatric assessment, including anamnesis, clinical evaluation, and laboratory testing focused on cardiovascular risk factors. The prevalence of CVD and the use of specific cardiovascular medications were analyzed. Results: Patients at high risk of falling showed significant differences compared to the control group in several parameters, including systolic blood pressure (SBP: 140.41 mmHg vs. 151.28 mmHg, p = 0.001), ankle brachial index (left ABI: 1.09 vs. 1.15., p = 0.033), and presence of cardiovascular diseases (p = 0.001), as well as total cholesterol (p = 0.005) and triglyceride levels (p = 0.047). Certain cardiovascular medications were significantly associated with increased fall risk, including spironolactone (OR = 4.10, p = 0.001), beta-blockers (OR = 1.88, p = 0.031), and calcium channel blockers (OR = 2.05, p = 0.014), especially in combination with one another. Additional risk factors included frailty, cognitive impairment, diabetes, and neurological or osteoarticular conditions. Interventions such as medication review, deprescribing, and dosage adjustments may help reduce fall risk without compromising cardiovascular disease management. Conclusions: Cardiovascular diseases and related pharmacotherapy are significantly associated with an increased risk of falls in older adults. Regular medication reviews, deprescribing where appropriate, and individualized treatment plans may help minimize fall risk while maintaining the effective cardiovascular care of this vulnerable population. Full article

Background/Objectives: We sought to determine if glibenclamide, a sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel blocker, reduces cerebral edema and improves neurological functioning in aneurysmal subarachnoid hemorrhage (aSAH). Methods: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted in PubMed, Cochrane Library, Web of Science, and SCOPUS for studies evaluating glibenclamide in aSAH patients. Primary outcomes included scores on the modified Rankin Scale (mRS) at discharge and the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) at ten days post-intervention. Secondary outcomes included adverse events, and safety and efficacy endpoints. Random-effects models were employed for meta-analyses. Results: Three studies utilizing oral glibenclamide (n = 245) met inclusion criteria. Oral glibenclamide demonstrated no significant improvements in mRS scores [MD −0.19 with 95% CI (−2.05, 1.66)] at discharge, [MD 0.06, (−0.60, 0.71)] at 3 months, and [MD 0.4, (−0.67, 0.87)] at 6 months; functional independence [risk ratio (RR) 1.05, (0.81, 1.36)]; independent ambulation [RR 1.07, (0.77, 1.48)]; mortality [RR 0.79, (0.42, 1.50)]; or delayed cerebral ischemia [RR 0.58, (0.31, 1.09]). Hypoglycemia risk was significantly higher in the glibenclamide group [RR 3.92, (1.14, 13.49)]. Conclusions: Oral glibenclamide offers a novel approach to addressing cerebral edema in aSAH but shows limited clinical efficacy in improving functional and neurological outcomes in subtherapeutic doses. Its safety profile is acceptable, though hypoglycemia risk necessitates careful monitoring. Further research is required to optimize dosing, timing of intervention, and patient selection to enhance therapeutic outcomes. By contrast, intravenous administration of therapeutic doses of glibenclamide offers a promising avenue for future studies in the management of aSAH by taking advantage of the favorable pharmacokinetics of this route of administration. Full article

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction. Full article

Cancer therapy-induced hypertension (HTN) is an increasingly recognized complication associated with a wide range of anticancer agents, including vascular endothelial growth factor (VEGF) inhibitors, proteasome inhibitors, tyrosine kinase inhibitors, and alkylating agents. The pathogenesis of HTN in this setting is multifactorial, involving mechanisms such as endothelial dysfunction, nitric oxide (NO) suppression, sympathetic nervous system activation, and vascular remodeling. Additional factors, including paraneoplastic syndromes, poorly controlled pain, mood disturbances, and overlapping cardiovascular risk factors like obesity and diabetes, further contribute to the complexity of diagnosis and management. Despite its prevalence and clinical implications, cancer therapy-induced HTN is often addressed using general population guidelines, with limited oncology-specific protocols available. Accurate blood pressure measurement and individualized treatment plans are critical to optimize outcomes and avoid interruptions to cancer therapy. Antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), and calcium channel blockers have shown efficacy in both blood pressure control and, in some cases, oncologic outcomes. A multidisciplinary approach involving oncologists, cardiologists, and primary care providers is essential to navigate the interplay between cancer treatment and cardiovascular health. Ongoing research is needed to develop targeted guidelines and improve the long-term care of cancer patients affected by treatment-induced HTN. Full article

Calcium (Ca²⁺) signaling is a fundamental regulatory mechanism controlling essential processes in the endothelium, vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM), including maintaining the endothelial barrier, modulation of vascular tone, and vascular remodeling. Cytosolic free Ca²⁺ concentration is tightly regulated by a balance between Ca²⁺ mobilization mechanisms, including Ca²⁺ release from the intracellular stores in the sarcoplasmic/endoplasmic reticulum and Ca²⁺ entry via voltage-dependent, transient-receptor potential, and store-operated Ca²⁺ channels, and Ca²⁺ elimination pathways including Ca²⁺ extrusion by the plasma membrane Ca²⁺-ATPase and Na⁺/Ca²⁺ exchanger and Ca²⁺ re-uptake by the sarco(endo)plasmic reticulum Ca²⁺-ATPase and the mitochondria. Some cell membranes/organelles are multifunctional and have both Ca²⁺ mobilization and Ca²⁺ removal pathways. Also, the individual Ca²⁺ handling pathways could be integrated to function in a regenerative, capacitative, cooperative, bidirectional, or reciprocal feed-forward or feed-back manner. Disruption of these pathways causes dysregulation of the Ca²⁺ signaling dynamics and leads to pathological cardiovascular conditions such as hypertension, coronary artery disease, atherosclerosis, and vascular calcification. In the endothelium, dysregulated Ca²⁺ signaling impairs nitric oxide production, reduces vasodilatory capacity, and increases vascular permeability. In VSMCs, Ca²⁺-dependent phosphorylation of the myosin light chain and Ca²⁺ sensitization by protein kinase-C (PKC) and Rho-kinase (ROCK) increase vascular tone and could lead to increased blood pressure and hypertension. Ca²⁺ activation of matrix metalloproteinases causes collagen/elastin imbalance and promotes vascular remodeling. Ca²⁺-dependent immune cell activation, leukocyte infiltration, and cholesterol accumulation by macrophages promote foam cell formation and atherosclerotic plaque progression. Chronic increases in VSMCs Ca²⁺ promote phenotypic switching to mesenchymal cells and osteogenic transformation and thereby accelerate vascular calcification and plaque instability. Emerging therapeutic strategies targeting these Ca²⁺-dependent mechanisms, including Ca²⁺ channel blockers and PKC and ROCK inhibitors, hold promise for restoring Ca²⁺ homeostasis and mitigating vascular disease progression. Full article

Background and Objectives: Up to 40% of patients undergoing a coronary angiogram due to angina pectoris have no obstructive coronary artery disease, also known as angina with non-obstructive coronary arteries (ANOCA). ANOCA is associated with significant impairment in patients’ quality of life, increased risk of myocardial infarction and all-cause mortality. Approximately 25% of patients with ANOCA have persisting symptoms despite optimal medical therapy. There is a lack of in-depth knowledge regarding tailored treatment for patients with ANOCA due to a scarcity of trials designed to assess the effect of treatment modalities. The aim of this systematic review and meta-analysis is to give clinicians an overview of the efficacy of current treatment modalities for patients with ANOCA. Methods: PudMed/MEDLINE, Embase, the Cochrane Library and clinical trial registries were searched for randomised controlled and cohort studies regarding treatment modalities for ANOCA. The main outcome was change in angina pectoris frequency for each treatment modality. Secondary outcomes included changes in exercise capacity, quality of life, Canadian Cardiovascular Society (CCS) class, coronary flow reserve (CFR) and survival. Results: In total, 80 studies were included and used in the meta-analysis, of which ten studies met the current definition of ANOCA. Angina pectoris frequency improved significantly in the majority of the treatment modalities, with neuromodulation resulting in −3.35 standardised mean difference (SMD) (95% CI: −5.13; −1.56), trimetazidine in −1.74 SMD (−2.63; −0.85), traditional Chinese medicine in −1.55 SMD (−2.36; −0.75), beta-blockers in −1.32 SMD (−1.88; −0.77), enhanced external counterpulsation in −1.27 SMD (−2.04; −0.49), stem cell therapy in −1.04 SMD (−1.51; −0.57), lifestyle interventions in −0.86 SMD (−1.15; −0.57), RAAS-inhibitors in −0.83 SMD (−1.31; −0.35) and calcium channel blockers in −0.64 SMD (−0.92; −0.35). Conclusions: This meta-analysis into treatment modalities for patients with ANOCA shows a significant improvement in angina pectoris frequency in the majority of included treatment modalities. However, these results should be interpreted cautiously, as only ten of the studies included in the meta-analysis meet the current definition of ANOCA. This review underlines the importance of undertaking new studies with existing treatment modalities to determine the efficacy in patients with ANOCA. Full article

Background: Severe poisoning can lead to catastrophic cardiovascular collapse, often progressing to multiorgan failure and death. While intensive supportive care and pharmacological intervention remain the cornerstone of management, cases of refractory cardiogenic shock, particularly those caused by membrane stabilizing agents and calcium channel blockers, pose a significant therapeutic challenge. Extracorporeal membrane oxygenation (ECMO) has emerged as a potential life-saving intervention in critically ill patients. This review examines the feasibility, clinical outcomes, and optimal indications for ECMO in the management of drug-induced cardiogenic shock. Methods: A systematic narrative review was conducted to evaluate the current evidence of ECMO use in poisoning-related cardiovascular failure, with a particular focus on patient selection criteria and the prognostic determinants of therapeutic resistance. Results: Extracorporeal membrane oxygenation may serve as a crucial hemodynamic support strategy in drug-induced circulatory collapse. Most reported cases involve peripheral ECMO, demonstrating variable but promising survival outcomes. Conclusions: Despite its potential to rescue patients from otherwise fatal toxic cardiomyopathy, the role of ECMO remains incompletely defined. Further prospective studies are essential to refine patient selection criteria and identify the toxicant-specific predictors of therapeutic failure. A deeper understanding of these factors may enhance clinical decision making and improve survival rates in severe poisoning cases. Full article

This work studies the effect of mesostructured silica–zirconia–tungstophosphoric acid (SiO₂-ZrO₂-TPA) composites used as catalysts in the synthesis of nifedipine by the Hantzsch methodology. The selectivity for nifedipine is determined, along with that of secondary products that may form depending on the reaction conditions. The materials were synthesized via the sol–gel method and characterized by N₂ adsorption–desorption isotherms, infrared spectroscopy (FT-IR), ³¹P solid-state nuclear magnetic resonance (NMR-MAS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), X-ray photoelectron spectra (XPS), and potentiometric titration. The characterization results from the XPS spectra showed that as the Si/Zr ratio drops, the Si-O-Si signal size decreases, while the Zr-O signal size increases. Characterization by titration indicated that an increase in the total acidity of the material, resulting from support modification with tungstophosphoric acid (H₃PW₁₂O₄₀, TPA), enhances the reaction yield. The catalytic activity in the solvent-free Hantzsch reaction was evaluated under thermal heating and microwave irradiation. The experiments conducted at 80 °C achieved a maximum yield of 57% after 4 h of reaction using the Si20Zr80TPA30 catalyst (50 mg), while by microwave heating, the yield significantly improved, reaching 77% in only 1 h of reaction. This catalyst exhibited stability and reusability without significant loss of activity up to the third cycle. Depending on the type of material and the reaction conditions, it is possible to modify the selectivity of the reaction, obtaining a 1,2-dihydropyridine isomeric to nifedipine. Reaction intermediates and other minor secondary products that may be formed in the process were also evaluated. Full article

Background: Patients with arrhythmias, particularly paroxysmal supraventricular tachycardia (PSVT), face an increased risk of cardiac complications. Currently, non-parenteral medications for rapid PSVT cessation are lacking. Etripamil, a novel intranasal, short-acting calcium channel blocker, offers a rapid onset and the potential for unsupervised PSVT management. However, data on its use in arrhythmia management remain limited. Aims: We aimed to assess the efficacy and safety of 70 mg of etripamil compared with placebo in the treatment of PSVT. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) from inception to April 2025. We calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs) using random or common effects models, depending on the heterogeneity. Results: Four RCTs including 540 patients were analyzed. Etripamil demonstrated higher conversion rates to the sinus rhythm at 15 min (RR 1.84 [95% CI: 1.32–2.48]), 30 min (RR 1.80 [95% CI: 1.38–2.35]), and 60 min (RR 1.24 [95% CI: 1.04–1.48]). PSVT recurrence rates were similar between groups (RR 0.52 [95% CI: 0.20–1.34]). Adverse events (AEs) and severe AEs were comparable between etripamil and the placebo. Etripamil was associated with higher rates of nasal discomfort, nasal congestion, rhinorrhea, and epistaxis but not with increased bradyarrhythmia, atrial fibrillation, or non-sustained ventricular tachycardia. Conclusions: Etripamil appears to be a promising treatment for cardiac arrhythmias. Larger long-term RCTs are needed to confirm its safety and efficacy in clinical practice. 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

Background/Objectives: Haloxylon griffithii is a medicinal plant possessing therapeutic effects in disorders associated with the gastrointestinal (GIT) system. This research aims to study the pharmacological activity of Haloxylon griffithii in a multidimensional manner, involving phytochemistry screening and in vitro and in vivo experiments. Methods: The whole dried plant was extracted with 80% methanol and further fractionation using solvents of increasing polarity. GC-MS analysis was performed on the crude extract to discover volatile compounds. The spasmolytic/spasmogenic effect was assessed in isolated rabbit jejunum using spontaneous and K⁺-induced contractions, as well as contractions induced by increasing concentrations of calcium ions in depolarized tissue. Antidiarrheal activity was evaluated in Swiss albino rats/mice (n = 6/group) using castor oil-induced diarrhea and peristaltic index models. In silico ADMET screening was conducted via SwissADME and pkCSM. Results: The GC-MS profiling of H. griffithii revealed the presence of 59 phytochemicals and a rare azulene derivative and constituents, including α-santonin and hexadecanoic acid esters, with favorable pharmacokinetic profiles, as predicted using SwissADME and pkCSM computational tools. The in vitro and in vivo experiments revealed the significant calcium channel blocking activity in non-polar fractions (n-hexane and ethyl acetate), while the polar extracts (ethanolic, aqueous) exhibited cholinergic effects, indicating a dual mode of action. Conclusions: This was a first-time demonstration of both antidiarrheal and smooth muscle-relaxant activity in H. griffithii, supported by GC-MS profiling and pharmacological assay. The findings lend scientific credibility to the traditional use of the plant in community healthcare, while also reinforcing the need for further pharmacological and clinical studies to explore its potential in drug development. Full article

Hypertrophic cardiomyopathy (HCM) is often associated with left ventricular outflow tract (LVOT) obstruction, which affects a substantial proportion of patients. This obstruction results from a range of anatomical abnormalities involving both the valvular and subvalvular structures. Pharmacological therapies play a pivotal role in the management of LVOT obstruction, with a range of drug classes exhibiting distinct mechanisms of action. Beta-blockers, including atenolol and nadolol, are considered the first-line treatment due to their ability to reduce heart rate and myocardial contractility and enhance diastolic filling. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, are utilized as second-line agents when beta-blockers are ineffective or contraindicated. Disopyramid, a Class 1A antiarrhythmic agent, is employed for patients who do not respond to initial therapeutic interventions and can reduce LVOT gradients. Recent advancements in cardiac myosin modulators, such as Mavacamten and Aficamten, offer targeted therapies by modulating myosin–actin interactions to reduce LVOT gradients and improve symptoms, with promising results from clinical trials. Although gene therapy is still in its nascent stages, it has the potential to address the genetic basis of HCM by employing techniques such as genome editing, gene replacement, and the modulation of signaling pathways. For patients exhibiting severe symptoms or demonstrating unresponsiveness to medical treatment, invasive therapies, such as septal reduction therapy and alcohol septal ablation, are considered. Ultimately, the treatment and prevention of atrial fibrillation and sudden cardiac death are two key points of HCM management in both obstructive and non-obstructive forms. This review aims to provide an overview of current pharmacological and invasive strategies, as well as emerging therapies, in the management of HCM. Full article