Calcium Channel Blockers Research Articles

Clinically approved representative small-molecule drugs for cardiopathy therapy.

The application of therapeutic agents for cardiopathy has brought about significant advancements in the treatment of cardiovascular diseases. The intervention of small-molecule drugs has led to substantial reductions in morbidity and mortality rates, along with decreased utilization of healthcare resources. However, current treatment modalities do not exhibit uniform efficacy across all patients, and the emergence of drug resistance poses a significant challenge to further therapeutic efforts. Additionally, chronic administration of these drugs can result in toxicities, adding complexity to long-term management. This review focuses on the application of clinically approved small-molecule drugs for the treatment of cardiopathy, covering major classes such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, β-blockers, and sodium-glucose co-transporter 2 inhibitors. The review provides an in-depth analysis of their synthetic routes, mechanisms of action, and roles in cardiopathy treatment. It also offers perspectives on future directions in the development of next-generation cardioprotective agents, aiming to optimize therapeutic strategies for cardiovascular disease management.

Endothelium-independent vasorelaxant effects of Curcuma phaeocaulis essential oil and its representative compound isocurcumenol.

The rhizomes of Curcuma phaeocaulis Val. are a Rhizoma curcumae source in Chinese pharmacopoeia, and this traditional Chinese medicine has been extensively used in China to promote blood circulation and remove blood stasis. However, little is known regarding the vasodilatory effects and underlying mechanisms. This study investigated the vasorelaxant effects and mechanisms of C. phaeocaulis essential oil (CPEO) and its representative compound, isocurcumenol. The effects of CPEO and isocurcumenol on the contractile tension of isolated rat thoracic aortic rings in a resting state and a KCl or phenylephrine (PHE) preincubation state in the tissue organ bath system were studied. The potential vasodilatory mechanisms of CPEO and isocurcumenol were investigated using a series of experiments that included endothelium removal, CPEO and isocurcumenol preincubation, extracellular Ca2+-induced contraction and intracellular Ca2+ release, and incubation with various blockers. Laser confocal microscopy was used to evaluate the effect of isocurcumenol on the intracellular Ca2+ fluorescence intensity in A7r5 cells. The influence of isocurcumenol on the myosin light chain (MLC) protein expression and phosphorylation was determined using a Western blot assay. Furthermore, the whole-cell patch clamp technique was used to investigate the effect of isocurcumenol on voltage-dependent K⁺channel (Kv) current cells. CPEO (0.25-25mg/L) and isocurcumenol (0.25-25μM) exhibited concentration-dependent vasodilatory effects on endothelial intact vascular rings that were pre-contracted using KCl or PHE. These vasodilatory effects did not significantly change after the endothelium was removed. Notably, the vasodilatory effects of the CPEO and isocurcumenol were attenuated when preincubation was performed using with 4-aminopyridine (4-AP, a Kv channel blocker) or verapamil hydrochloride (an L-type calcium channel blocker). In the cell experiments, isocurcumenol suppressed an increase in the Ca2+ fluorescence intensity and inhibited the phosphorylation of the MLC protein in A7r5 cells. The results of the whole-cell patch clamp assay indicated that 25μM of isocurcumenol enhanced Kv channel currents. In this study, we confirmed that CPEO and isocurcumenol had significant endothelium-independent vasorelaxant effects. The underlying mechanism was attributed to the activation Kv channels and the suppression of L-type calcium channels. This resulted in a Ca2+ influx decrease in vascular smooth muscle cells and subsequent vascular contraction inhibition.

The calcium channel blocker nimodipine inhibits spinal reflex pathways in humans.

Voltage-sensitive calcium channels contribute to depolarization of both motor neurons and interneurons in animal studies, but less is known of their contribution to human motor control and whether blocking them has potential in future antispasmodic treatment in humans. Therefore, this study investigated the acute effect of nimodipine on the transmission of human spinal reflex pathways involved in spasticity. In a double-blinded, crossover study, we measured soleus muscle stretch reflexes and H reflexes and tibialis anterior cutaneous reflexes in 19 healthy subjects before and after nimodipine (tablet 60 mg) or baclofen (tablet 25 mg). Baclofen was used as a control to compare nimodipine's effects with known antispastic treatment. Changes in the size of the maximum H reflex (Hmax)/maximum direct motor response in muscle (Mmax) ratio and stretch and cutaneous reflexes following intervention with nimodipine and baclofen, respectively, were analyzed with a one-way repeated-measures (RM) ANOVA. Nimodipine significantly reduced the Hmax/Mmax ratio [F(2.5,42) = 15; P < 0.0001] and the normalized soleus stretch reflex [F(2.6,47) = 4.8; P = 0.0073] after administration. A similar tendency was seen after baclofen [Hmax/Mmax ratio: F(2.1,39) = 4.0, P = 0.024; normalized stretch reflex: F(2.8,50) = 2.4; P = 0.083]. The Mmax response was unaffected by either intervention. Interestingly, during voluntary soleus activation, the stretch reflex remained unchanged with either treatment. For the cutaneous reflexes, there was a trend toward reduced early inhibition [F(1.6,9.3) = 4.5; P = 0.050] and subsequent facilitation [F(1.3,8.0) = 4.3; P = 0.065] after nimodipine. No severe adverse effects were reported after nimodipine. These findings suggest that nimodipine acutely reduced electrophysiological measures related to spasticity in healthy individuals. The effect seemed located at the spinal level, and voluntary contraction counterbalanced the reduction of the stretch reflex, highlighting its relevance for future studies on antispastic therapies.NEW & NOTEWORTHY The calcium channel antagonist nimodipine significantly reduces the size of the soleus H reflex and stretch reflex in healthy individuals without affecting maximum direct motor response (Mmax) or the stretch reflex during voluntary activation. This underscores the importance of exploring nimodipine as a potential antispastic medication in the future.

The effect of disopyramide therapy on functional capacity improvement in patients with obstructive hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular outflow tract obstruction (LVOTO), leading to symptoms and adverse outcomes. Disopyramide, with its negative inotropic effects, is commonly used to reduce LVOTO in obstructive HCM (HOCM). This study evaluates the impact of disopyramide on functional capacity in HOCM patients. Symptomatic HOCM patients evaluated between October 2021 and May 2024 were divided into two groups: those receiving disopyramide and those treated with beta-blockers or calcium channel blockers due to disopyramide unavailability. A treatment response was defined as at least a 1-stage improvement in NYHA class. Clinical and laboratory data, including NT-proBNP levels and LVOT gradient, were compared between groups. A total of 127 patients were included (median age 54.0years, 58.2% male). 79% of patients were in NYHA class 2. After follow-up, 62% of the disopyramide group (the mean follow-up duration was 15.2months, and the mean daily dose was 395mg) showed at least a 1-stage improvement in functional capacity, compared to 26% in the control group. Disopyramide use and presence of extent LGE were independent predictors of functional improvement. Despite functional gains, there was no difference in overall clinical outcomes between the groups. Disopyramide-related side effects were minimal, and no patients discontinued due to QT prolongation. Disopyramide significantly improved functional capacity in HOCM patients, with 62% achieving a 1-stage NYHA improvement compared to 26% in the control group. These results highlight the need for better accessibility to disopyramide in regions where it is difficult to obtain.

Differences between private and public primary health care centers and differences between men and women in antihypertensive care and cardiovascular prevention in all patients with hypertension treated in primary care in Stockholm County, Sweden

AimsTo study differences in cardiovascular prevention and hypertension management in primary care in men and women, with comparisons between public and privately operated primary health care (PHC).MethodsWe used register data from Region Stockholm on collected prescribed medication and registered diagnoses, to identify patients aged 30 years and above with hypertension. Age-adjusted logistic regression was used to calculate odds ratios (ORs) with 99% confidence intervals (99% CIs) using public PHC centers as referents.ResultsIn total, 119,267 patients with a registered hypertension diagnosis at their primary care center were included; 58,239 men and 61,028 women. In terms of co-morbidities and medications, there were some differences between privately and publicly run PHC: registered diagnosis of dementia, which was higher at private PHC, age-adjusted OR 1.80 (1.24–2.69). For lifestyle counseling, privately run PHC had a higher rate of registered counseling for tobacco 1.17 (1.06–1.29), physical activity 1.13 (1.06–1.17), unhealthy diet 1.08 (1.04–1.13), and counseling according to highest prioritized level of advice stated by national guidelines 1.14 (1.09–1.18). Differences in comorbidities between men and women were found, with higher frequencies of coronary heart disease, congestive heart failure, atrial fibrillation, stroke, diabetes, and gout among men. Regarding antihypertensive treatment, women received less treatment of calcium channel blockers and ACE inhibitors, but more of angiotensin receptor blockers.ConclusionsThese findings highlight the need for targeted preventive efforts in PHC, especially for male patients, to address disparities in cardiovascular health outcomes. Small differences in preventive measures between public and privately run PHC suggest generally consistent care across healthcare ownership models.

Lipid-Lowering and Antihypertensive Drugs on Aortic Disease Risk: Insights from Mendelian Randomization Analysis and Real-World Pharmacovigilance Data.

To assess the impact of lipid-lowering drugs (LLDs) and antihypertensive drugs on the risk of aortic diseases. Mendelian randomization was utilized to analyze data from 500,000 participants in the UK Biobank to evaluate the effects of statins, PCSK9 inhibitors (PCSK9i), beta-blockers, and calcium channel blockers on the risks of thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA), and aortic dissection (AD) using genetic variants as proxies. Real-world pharmacovigilance data from the FAERS database was used. PCSK9i and statins significantly reduced the risks of aortic aneurysms and AD, respectively. Furthermore, the two LLDs reduced the risk of aortic diseases through certain metabolites. Meanwhile, real-world pharmacovigilance reports also indicated a low incidence of aortic diseases with PCSK9i and statin treatment. LLDs, particularly statins and PCSK9i, significantly protect against aortic diseases, providing a scientific basis for preventing and treating aortic diseases.

Linear IgA bullous dermatosis secondary to drugs: a real-world pharmacovigilance study of the FDA adverse event reporting system

BackgroundLinear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disease. The induction of LABD by medications is a critical issue, with previous studies highlighting the link between specific drugs and the onset of LABD. This study aims to assess the reported associations between LABD and numerous available medications using the FDA adverse event reporting system (FAERS).MethodsThe study encompassed FAERS reports spanning the years 2004–2024. Medical Dictionary for Regulatory Activities (MedDRA) was used to identify cases of LABD. The Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayes Geometric Mean were calculated to assess the reported associations between available drugs and LABD. A significant statistical association was considered when a drug signal met the criteria of all four algorithms.ResultsIn the FAERS database analysis, we identified 1,394 adverse event (AE) reports associated with LABD. The gender distribution of reports was relatively balanced, with the highest proportion in the 66–85 age group. The United States had the highest number of reports. Vancomycin and Amoxicillin were the most frequently reported drugs, with 559 and 58 reports, respectively. Through disproportionality analysis, we identified 34 drugs significantly associated with AEs of LABD, including antibiotics, antifungal medications, analgesics, nonsteroidal anti-inflammatory drugs, cardiovascular medications, and calcium channel blockers, among which the antibiotic Vancomycin showed the highest association. These results emphasize the need for further clinical attention to the safety of specific medications.ConclusionThis is the first real-world study using the FAERS database to investigate drug-induced LABD. LABD is closely associated with antibiotic medications. Close monitoring of patients is required when these medications are used clinically to promptly detect and manage potential AEs such as LABD.

Systematic Review of the Impact of Calcium Channel Blockers on Sperm Function.

This study explores the effects of calcium channel blockers (CCBs) on sperm function, a critical aspect of male fertility. Male infertility, responsible for 30-50% of infertility cases, often involves issues with sperm motility and capacitation, both of which are heavily influenced by calcium ions and specific ion channels like CatSper and voltage-dependent calcium channels (VDCCs). CCBs, which are commonly prescribed for cardiovascular conditions, inhibit these calcium channels, potentially disrupting sperm function. A comprehensive literature review showed varied results: some studies demonstrated that CCBs such as nifedipine reduce sperm motility and the acrosome reaction, causing reversible infertility, while others found no significant impact on fertilization rates in IVF treatments. Supporting these findings, animal studies indicated that CCBs impair spermatogenesis and sperm function without necessarily affecting hormonal levels. The research suggests that the impact of CCBs on male fertility might be reversible, emphasizing the need for more extensive in vivo studies to further understand these effects and their clinical significance for patients on CCB therapy.

COST MINIMIZATION ANALYSIS OF ANTIHYPERTENSIVE DRUG USE IN CHRONIC KIDNEY DISEASE PATIENTS UNDERGOING HEMODIALYSIS

Hypertension is the primary cause of Chronic Kidney Disease (CKD), as it damages blood vessels in the kidneys. The most commonly used management for hypertension as monotherapy includes Calcium Channel Blockers (CCB) such as Amlodipine and Angiotensin Receptor Blockers (ARB) such as candesartan. Patients with CKD undergoing hemodialysis depend on dialysis machines, which impacts their economic burden. Therefore, a cost analysis review of drugs with the same therapeutic goals is necessary. This was a non-experimental study with a descriptive design. Data were collected through retrospective purposive sampling from January to December 2023 using medical records and payment data for inpatient treatments with hemodialysis that met the inclusion criteria. Direct medical costs included antihypertensive, other medication, service and facility fees, and medical support costs. Of the 100 samples that met the inclusion criteria from January to December 2023, amlodipine was the most commonly used antihypertensive (56%), followed by candesartan (38%). The average direct medical costs were IDR 184.350 for Amlodipine and IDR 561,339 for candesartan. The patient characteristics by gender showed a higher percentage of males (52%) than of females (48%). By age, the majority were in the late adult group (67%), whereas the elderly accounted for (33%). The Amlodipine group achieved more significant cost minimization than the candesartan group. Future studies should examine the potential of amlodipine in reducing the economic burden of limited resources. Keywords: antihypertensive, CMA, CKD

Clinical burden of obstructive hypertrophic cardiomyopathy in France

BackgroundHypertrophic cardiomyopathy (HCM) can be genetic and occurs as obstructive and non-obstructive 21 subtypes. Little is known about the clinical burden of the obstructive subtype of HCM at a national 22 level, and how it may differ by New York Heart Association (NYHA) class. Therefore, this study 23 aimed to describe the clinical burden of patients hospitalized with obstructive HCM from a 24 nationwide study in France.MethodsThis retrospective, longitudinal, observational study was performed using data from the French National Health Data System. All adult patients (≥ 18 years old) with a hospitalization related to obstructive HCM [International Classification of Diseases, Tenth Revision (ICD-10) code I42.1], or at least one hospitalization with ICD-10 code I42.2 or I42.9 and at least one code for septal reduction therapy between 2012 and 2018 were included. Patients were followed up for a minimum of 1 year. NYHA class was assigned using an algorithm based on treatment and symptom codes. Treatment patterns and clinical outcomes by NYHA class over time were examined.ResultsOverall, 6,823 patients with obstructive HCM were included (54.7% male, mean [standard deviation (SD)] age 66.2 [16.7] years). At inclusion, the proportion of patients in NYHA classes I, II, III, and IV were 4%, 32%, 60%, and 4%, respectively. Over the follow-up [mean (SD) follow-up: 4.4 (2.5) years; cumulative patient follow-up: 30,021 patient-years], 73% of patients remained in the same NYHA class, 14% of patients worsened, and 13% improved. At inclusion, 22% of patients had no HCM-related treatment, 56% were receiving β-blockers, 12% calcium-channel blockers, and 11% a combination of both. The incidence of cardiovascular-related hospitalization was high (35,436 hospitalizations; 117,229 per 100,000 patient-years) and this risk increased with NYHA class (from 81,247 per 100,000 patient-years for NYHA class I/II patients to 140,790 per 100,000 patient-years for NYHA class III/IV patients, p &amp;lt; 0.0001).ConclusionsPatients with obstructive HCM are at high risk of death and cardiovascular outcomes, especially those in higher NYHA classes. Despite current therapeutics, the clinical burden of symptomatic obstructive HCM remains high, supporting the need for additional therapies.

The Protective Effect of Nimodipine in Schwann Cells Is Related to the Upregulation of LMO4 and SERCA3 Accompanied by the Fine-Tuning of Intracellular Calcium Levels.

Nimodipine is the current gold standard in the treatment of subarachnoid hemorrhage, as it is the only known calcium channel blocker that has been proven to improve neurological outcomes. In addition, nimodipine exhibits neuroprotective properties in vitro under various stress conditions. Furthermore, clinical studies have demonstrated a neuroprotective effect of nimodipine after vestibular schwannoma surgery. However, the molecular mode of action of nimodipine pre-treatment has not been well investigated. In the present study, using real-time cell death assays, we demonstrated that nimodipine not only reduces cell death induced by osmotic and oxidative stress but also protects cells directly at the time of stress induction in Schwann cells. Nimodipine counteracts stress-induced calcium overload and the overexpression of the Cav1.2 calcium channel. In addition, we found nimodipine-dependent upregulation of sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (SERCA3) and LIM domain only 4 (LMO4) protein. Analysis of anti-apoptotic cell signaling showed an inhibition of the pro-apoptotic protein glycogen synthase kinase 3 beta (GSK3β). Nimodipine-treated Schwann cells exhibited higher levels of phosphorylated GSK3β at serine residue 9 during osmotic and oxidative stress. In conclusion, nimodipine prevents cell death by protecting cells from calcium overload by fine-tuning intracellular calcium signaling and gene expression.

The additional impact of metabolic syndrome on left ventricular deformation and myocardial energetic efficiency impairment in ischemia with nonobstructive coronary arteries patients

BackgroundIschemia with nonobstructive coronary arteries (INOCA) has high morbidity, mortality, and poor quality of life. Metabolic syndrome (MetS) is a complex of multiple cardiac metabolic risk factors, significantly increasing the risk of major adverse cardiovascular events in INOCA patients. The study aimed to investigate the aggravating effect of MetS on left ventricular (LV) deformation and function impairment in INOCA patients.Materials and methods This study collected 104 INOCA patients (INOCA [MetS−]: n = 56; INOCA [MetS+]: n = 48) and 41 sex- and age-matched controls. LV function, indexed myocardial energetic efficiency (MEEI), and LV global peak strains (including radial, circumferential, and longitudinal directions) were measured among the three groups. The independent factors of reduced MEEI and impaired LV function and strain parameters for all INOCA patients were assessed using multivariable linear regression analyses.ResultsIn contrast to the INOCA (MetS-) group, the indexed LV stroke volume (LVSVI) (49.57 ± 11.58 mL/m2 vs. 42.58 ± 12.23 mL/m2, p = 0.007), MEEI [0.85(0.70–1.03) ml/s/g vs. 0.75(0.54–0.91) ml/s/g, p = 0.045] and LV global longitudinal peak strain (GLPS) (− 13.26 ± 2.86% vs. -10.95 ± 3.93%, p = 0.001) reduced in the INOCA (MetS+) group. Compared with the controls, LV GLPS decreased in the INOCA (MetS-) group (− 15.14 ± 2.83% vs. −13.26 ± 2.86%, p = 0.017). MetS was negatively associated with LVSVI, MEEI, and LV GLPS (all p < 0.05). After multivariable adjustment, MetS was found to be an independent factor of decreased LVSVI (β = −0.231, p = 0.012), MEEI (β = −0.262, p = 0.009), and LV GLPS (β = −0.266, p = 0.002) in INOCA patients. Using calcium channel blockers medication (β = 0.320, p = 0.001) and hypertension (β = −0.298, p = 0.002) were also independently associated with impaired MEEI.ConclusionsMetS aggravated LV deformation and function impairment in patients with INOCA. MetS was found to be an independent factor of impaired MEEI and LV GLPS, the further decrease of MEEI and LV GLPS in INOCA patients caused by MetS might involve the synergistic injury mechanism. Early diagnosis and treatment of MetS in patients with INOCA are important.

Gender inequalities in prescribing and initiation patterns of guideline-recommended drugs after acute myocardial infarction

BackgroundEuropean guidelines recommend the prescription of certain drugs after acute myocardial infarction (AMI). The existence of gender differences in pharmacological treatment after an AMI has been described. This study aims to describe and analyse, using real-world data (RWD), whether there are gender differences in the prescribing patterns and initiation of treatment in secondary prevention after a first AMI, and which are the factors that explain these differences.MethodsA population-based observational study of RWD was conducted in the CARhES (CArdiovascular Risk factors for hEalth Services research) cohort. The study included subjects who had experienced a first episode of AMI between 2017 and 2022, had survived the event, and had a minimum follow-up of 180 days.Results3,975 subjects were followed 180 days after a first AMI. Women (27.8% of the study population) were older and had more comorbidities. Of the main guideline-recommended drugs, antiplatelets, lipid modifying agents and beta-blockers, were prescribed less often in women. Comedications such as rivaroxaban and calcium channel blockers were more likely to be prescribed in women. The proportion of subjects initiating treatment was similar in both genders.Overall, age and morbidity burden were the main contributors to differences in the prescribing patterns. Living in an urban area seemed to be a protective or mitigating factor. There were controversial results regarding socioeconomic level. ConclusionIn our study population, women are older, have greater comorbidities and lower socioeconomic status. Despite this, gender inequalities in the prescribing patterns after a first AMI remains, as women appear to experience less therapeutic effort. It is crucial to analyse them from an intersectional perspective, considering the influence of multiple axes of inequality on health, in order to develop gender-sensitive strategies with a multidisciplinary approach.

Blood Pressure Management Strategies and Podocyte Health.

Hypertension (HTN) is one of the key global cardiovascular risk factors, which is tightly linked to kidney health and disease development. Podocytes, glomerular epithelial cells that play a pivotal role in maintenance of the renal filtration barrier, are significantly affected by increased glomerular capillary pressure in HTN. Damage or loss of these cells causes proteinuria, which marks the initiation of the HTN-driven renal damage. It goes without saying that effective blood pressure (BP) management should not only mitigate cardiovascular risks but also preserve renal function by protecting podocyte integrity. This review offers a comprehensive examination of current BP management strategies and their implications for podocyte structure and function and emphasizes strategies for the reduction of proteinuria in HTN. We explore primary and secondary antihypertensive agents, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics, as well as newer therapies (sodium-glucose cotransporter-2 blocking and endothelin receptor antagonism), emphasizing their mechanistic roles in safeguarding podocytes and curtailing proteinuria.

Alcohol consumption and ambulatory blood pressure-lowering effect in male patients on clinic blood pressure-guided antihypertensive treatment.

In the present analysis, we investigated the association between alcohol consumption and ambulatory blood pressure (BP) control in male patients after 8 weeks of antihypertensive therapy with two dihydropyridine calcium channel blockers. The study participants were hypertensive (clinic systolic/diastolic BP of 140-179/90-109 mmHg and 24-hour ambulatory systolic/diastolic BP ≥ 130/80 mmHg) patients enrolled in a randomized controlled trial and treated with amlodipine 5-10 mg or nifedipine gastrointestinal therapeutic system (GITS) 30-60 mg once daily. Alcohol consumption was classified as non-drinkers and drinkers. Non-dipping was defined as a BP drop from daytime to nighttime <10%. At baseline, the 131 alcohol drinkers, compared with 141 non-drinkers, had a significantly higher nighttime systolic/diastolic BP (129.3 ± 13.5/83.8 ± 9.5 vs. 125.7 ± 12.3/80.9 ± 8.2 mmHg, P ≤ 0.02), night-to-day ratio for both systolic (89.1 ± 8.5 vs. 87.0 ± 7.1%, P = 0.03) and diastolic BP (88.7 ± 8.8 vs. 86.5 ± 7.9%, P = 0.04) and prevalence of non-dippers for systolic (45.0% vs. 33.3%, P = 0.048) and diastolic BP (42.0% vs. 29.8%, P = 0.04). However, they had similar clinic and 24-hour and daytime ambulatory BP at baseline (P ≥ 0.07). Antihypertensive treatment significantly (P ≤ 0.001) reduced clinic and ambulatory systolic and diastolic BP from baseline in both alcohol drinkers and non-drinkers at 4 and 8 weeks of follow-up. However, in patients with a non-dipping pattern at baseline, the proportion of dippers for systolic/diastolic BP at 8 weeks of follow-up (36.5% vs. 58.5%) was significantly lower in 67 alcohol drinkers than in 52 non-drinkers (P = 0.035). Alcohol drinkers had higher nighttime BP and a higher prevalence of non-dippers than non-drinkers. Clinic blood pressure-guided antihypertensive treatment was insufficient in controlling nighttime BP or changing the non-dipping to dipping pattern in alcohol drinkers with sustained clinic and ambulatory hypertension. Alcohol drinkers had higher nighttime systolic and diastolic blood pressure than non-drinkers at baseline. Clinic blood pressure-guided antihypertensive treatment was insufficient in changing the non-dipping to dipping pattern in alcohol drinkers with sustained clinic and ambulatory hypertension.

Soluplus Stabilized Amorphous Dispersions for Enhanced Oral Absorption of Felodipine.

Overcoming the poor aqueous solubility of small-molecule drugs is a major challenge in developing clinical pharmaceuticals. Felodipine (FLDP), an L-type calcium calcium channel blocker, is a poorly water-soluble drug. The study aimed to explore the potential applications of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) stabilized amorphous dispersions for augmenting the oral delivery of poorly water-soluble drugs. Soluplus-stabilized amorphous FLDP (FLDP-SSAs) was prepared using a two-phase mixing method. The samples were analyzed for their microscopic and macroscopic behavior using polarized light microscopy (PLM), differential scanning calorimetry (DSC), molecular simulation, and in vitro dissolution studies. Subsequently, the pharmacokinetics of FLDP-SSAs were evaluated. The maximum drug-to-Soluplus mass ratio of FLDP-SSAs was 50:50, with a drug concentration of 8.0 mg/mL. They exhibited an amorphous nature, as confirmed by PLM and DSC. FLDPSSAs generated nanoparticles with a particle size of approximately 50 nm during in vitro dissolution. Compared to FLDP oral solution, FLDP-SSAs exhibited higher solubility due to their amorphous nature and the generation of nanoparticles. The area under the curve (AUC) for oral FLDP-SSAs was 16.7-fold larger than that of the FLDP suspension. FLDP-SSAs could stabilize FLDP in an amorphous state and serve as drug carriers to enhance oral absorption.

A Review on Method Development for the Analysis of Combine Product of Amlodipine Besilate and Rosuvastatin Calcium in Pharmaceutical Dosage form

Rosuvastatin belongs to the category of statins, used in combination with calcium channel blockers, analgesicsand other class of cardiovascular disease drugs in the treatment of high cholesterol and related conditions to prevent cardiovascular diseases. The clinical and pharmaceutical analysis of these drugs requires effective analytical procedures for quality control, pharmacodynamic and pharmacokinetic studies. An extensive survey of the literature published in various analytical and pharmaceutical chemistry related journals has been conducted and the instrumentalmethods which were developed and used for determination of Rosuvastatin in combined dosage forms have been reviewed. This review covers various analytical methods for estimation of Rosuvastatin calcium and Fenofibrate in combined dosage forms, such as spectrophotometry, derivative spectrophotometry and various highperformance liquid chromatographic (HPLC) methods that were published from 2010 to 2014. Key Words: Rosuvastatin, Fenofibrate, review, HPLC, Spectrophotometry

Interfacility Transfer for VA-ECMO in BB and CCB Overdoses: A Report of Two Cases

Introduction: Calcium channel blocker (CCB) and beta blocker (BB) overdoses are life-threatening conditions that can lead to vasoplegic and cardiogenic shock. Treatment involves a combination of vasopressors, calcium, glucagon, and/or high-dose insulin euglycemia therapy. The most severe overdoses may require venoarterial extracorporeal membrane oxygenation (VA-ECMO), which often results in interfacility transfers. This report describes two successful VA-ECMO transfers for refractory CCB/BB overdose. Case Reports: Case 1: A 56-year-old male developed severe hypotension after ingesting 40-45 tablets of 10 milligram (mg) amlodipine tablets. After initial treatment approaches were unsuccessful, an early interdisciplinary discussion facilitated timely cannulation at the initial facility and quick transfer for VA-ECMO initiation. The patient was discharged at his neurological baseline after 60 days. Case 2: A 19-year-old female presented to the emergency department after a polypharmacy ingestion including 60 tablets of 20 mg propranolol. An early interdisciplinary discussion between the medical intensive care unit, medical toxicology, and the ECMO team allowed for prompt transfer directly to the receiving hospital catheterization lab for VA-ECMO within three hours of the initial presentation. The patient was discharged to an inpatient psychiatric facility after nine days. Conclusion: Venoarterial extracorporeal membrane oxygenation for refractory shock due to CCB and BB overdoses can be a life-saving intervention. Interfacility transfer of poisoned patients for VA-ECMO is logistically challenging, which can delay the appropriate care for patients with an otherwise morbid prognosis. A streamlined interfacility transfer protocol with multidisciplinary collaboration can help optimize outcomes.

L-type Calcium Channel Blockade Worsens Glucose Tolerance and β-Cell Function in C57BL6/J Mice Exposed to Intermittent Hypoxia.

Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated. Adult male C57BL6/J mice were exposed to either nifedipine or vehicle concurrently with IH or intermittent air (IA) over five days. IH exposure entailed cycling fractional inspired oxygen levels between 0.21 and 0.055 at a rate of 60 events per hour. Nifedipine (20 mg/kg/day) or vehicle was administered via subcutaneous osmotic pumps resulting in four groups of mice: IA-vehicle (control), IA-nifedipine, and IH-vehicle, IH-nifedipine. Compared to IA (control), IH increased fasting glucose (Mean Δ:33.0 mg/dl; p<0.001) and insulin (mean Δ: 0.53 ng/ml; p<0.001) with nifedipine having no independent effect. Furthermore, glucose tolerance was worse with nifedipine alone, and IH further exacerbated the impairment in glucose disposal (p=0.013 for interaction). Nifedipine also decreased glucose-stimulated insulin secretion and the insulinogenic index, with addition of IH attenuating those measures further. There were no discernible alterations in insulin biosynthesis/processing, insulin content, or islet morphology. These findings underscore the detrimental impact of IH on insulin sensitivity and glucose tolerance, while highlighting that nifedipine exacerbates these disturbances through impaired β- cell function. Consequently, cautious use of L-type calcium channel blockers is warranted in OSA patients, particularly in those at risk for type 2 diabetes.

Novel ecofriendly spectrophotometric methods for the determination of six dihydropyridines calcium channel blockers through derivatization with sulfophtalein dye: application to tablet analysis

Novel, «green» and simple visible spectrophotometric procedures for the determination of six dihydropyridines CCBs (amlodipine besylate (AML), lacidipine (LAC), levamlodipine besylate (LAML), nifedipine (NIF), nimodipine (NIM) and nitrendipine (NIT)) through derivatization with the sulfophthalein dye bromophenol blue (BPB) have been developed. The optimal parameters for CCBs spectrophotometric analysis via complex formation using BPB were as follows: detection wavelength—596 nm, reaction time—5 min, ratio of reacting components—1:1, operating temperature—25 ± 2 °C. The concentration was linearly proportional to absorbance values in the range of 3.40—17.00 μg/mL (AML), 1.14—9.11 μg/mL (LAC), 1.14—9.08 μg/mL (LAML), 4.16—12.40 μg/mL (NIF), 0.84—5.86 μg/mL (NIM), 6.52—19.60 μg/mL (NIT). The developed methods are colorimetric and therefore does not require a UV instrument to quantify these drugs. The proposed approach was more efficient in terms of time reliability, sensitivity and «greenness» than other recorded spectrophotometric methods and can be easily implemented for routine pharmaceutical analysis.