The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}.

INTRODUCTION: Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30-60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. METHODS AND ANALYSIS: This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6-10 am) or a bedtime (6-10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. DISCUSSION: Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. TRIAL REGISTRATION: ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}.

Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.

BACKGROUND: Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018. OBJECTIVES: To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 µg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions. AUTHORS' CONCLUSIONS: The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.

Hordeum vulgare ethanolic extract mitigates high salt-induced cerebellum damage via attenuation of oxidative stress, neuroinflammation, and neurochemical alterations in hypertensive rats.

High salt intake increases inflammatory and oxidative stress responses and causes an imbalance of neurotransmitters involved in the pathogenesis of hypertension that is related to the onset of cerebral injury. Using natural compounds that target oxidative stress and neuroinflammation pathways remains a promising approach for treating neurological diseases. Barley (Hordeum vulgare L.) seeds are rich in protein, fiber, minerals, and phenolic compounds, that exhibit potent neuroprotective effects in various neurodegenerative diseases. Therefore, this work aimed to investigate the efficacy of barley ethanolic extract against a high salt diet (HSD)-induced cerebellum injury in hypertensive rats. Forty-eight Wistar rats were divided into six groups. Group (I) was the control. The second group, the HSD group, was fed a diet containing 8% NaCl. Groups II and III were fed an HSD and simultaneously treated with either amlodipine (1 mg /kg b.wt p.o) or barley extract (1000 mg /kg b.wt p.o) for five weeks. Groups IV and V were fed HSD for five weeks, then administered with either amlodipine or barley extract for another five weeks. The results revealed that barley treatment significantly reduced blood pressure and effectively reduced oxidative stress and inflammation in rat's cerebellum as indicated by higher GSH and nitric oxide levels and lower malondialdehyde, TNF-α, and IL-1ß levels. Additionally, barley restored the balance of neurotransmitters and improved cellular energy performance in the cerebellum of HSD-fed rats. These findings suggest that barley supplementation exerted protective effects against high salt-induced hypertension by an antioxidant, anti-inflammatory, and vasodilating effects and restoring neurochemical alterations.

Synergistic combination of carvedilol, amlodipine, amitriptyline, and antibiotics as an alternative treatment approach for the susceptible and multidrug-resistant A. baumannii infections via drug repurposing.

We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of Acinetobacter baumannii infections caused by susceptible and multidrug-resistant strains. A. baumannii is a multidrug-resistant Gram-negative bacteria causing nosocomial infections, especially in intensive care units. It has been identified in the WHO critical pathogen list and this emphasises urgent need for new treatment options. As the development of new therapeutics is expensive and time consuming, finding new uses of existing drugs via drug repositioning has been favoured. Antimicrobial susceptibility tests were conducted on all 13 drugs according to CLSI. Drugs with MIC values below 128 µg/mL and control antibiotics were further subjected to synergetic effect and bacterial time-kill analysis. Carvedilol-gentamicin (FICI 0.2813) and carvedilol-amlodipine (FICI 0.5625) were determined to have synergetic and additive effect, respectively, on the susceptible A. baumannii strain, and amlodipine-tetracycline (FICI 0.75) and amitriptyline-tetracycline (FICI 0.75) to have additive effect on the multidrug-resistant A. baumannii strain. Most remarkably, both amlodipine and amitriptyline reduced the MIC of multidrug-resistant, including some carbapenems, A. baumannii reference antibiotic tetracycline from 2 to 0.5 µg/mL, for 4-folds. All these results were further supported by bacterial time-kill assay and all combinations showed bactericidal activity, at certain hours, at 4XMIC. Combinations proposed in this study may provide treatment options for both susceptible and multidrug-resistant A. baumannii infections but requires further pharmacokinetics and pharmacodynamics analyses and in vivo re-evaluations using appropriate models.

Effects of Valsartan and Amlodipine Tablets Combined with α-Lipoic Acid on T-AOC, IL-6 and ß2-MG Levels in Patients with Diabetic Nephropathy.

Diabetic nephropathy (DN) is the most important cause of chronic renal and end-stage kidney disease in China. Hypertension (HTN) is highly prevalent in individuals with diabetic nephropathy. Arterial HTN affects two-thirds of people with type 2 diabetes (T2D). In these patients, HTN increased the potential of both micro- and macrovascular complications, and the co-occurrence of 2 such principal causes results in a 4-fold increased risk for cardiovascular disease (CVD) when contrasted with normotensive controls without diabetes. Therefore, the results of valsartan and amlodipine tablets combined with alpha-lipoic acid on total antioxidant capacity (T-AOC) need to be investigated. The aim of this study was to analyze the effects of valsartan (VA) and amlodipine tablets combined with alpha-lipoic acid (α-LA) on T-AOC, IL-6 and ß2-MG levels in patients with DN. We performed statistical analysis including the chi-square test, independent t-test, paired t-test and Analysis of Variance (ANOVA). Our findings indicate that VA, amlodipine and α-LA has a significant effect in patients with DN.

Single-Pill Combination with Three Antihypertensive Agents to Improve Blood Pressure Control in Hypertension: Focus on Olmesartan-Based Combinations.

Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients.

Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta-analysis with trial sequential analysis.

OBJECTIVES: Iron overload in patients with thalassemia represents a serious complication by affecting numerous organ systems. This meta-analysis aims to establish an evidence regarding the effect of amlodipine on cardiac iron overload in thalassemia patients. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials (RCTs). The primary outcomes were cardiac T2* and myocardial iron concentration (MIC). Secondary outcomes were liver iron concentration (LIC), risk of Gastrointestinal (G.I.) upset and risk of lower limb edema. We used Hedges' g to pool continuous outcomes, while odds ratio was used for dichotomous outcomes. RESULTS: Seven RCTs were eligible for this systematic review and meta-analysis, comprising of 233 patients included in the analysis. Amlodipine had a statistically significant lower MIC (Hedges' g = -0.82, 95% confidence interval [CI] [-1.40, -0.24], p < .001) and higher cardiac T2* (Hedges' g = 0.36, 95% CI [0.10, 0.62], p = .03). Amlodipine was comparable to standard chelation therapy in terms of the risk of lower limb edema and GI upset. CONCLUSION: Our meta-analysis found that amlodipine significantly increases cardiac T2* and decreases MIC, hence decreasing the incidence of cardiomyopathy-related iron overload in thalassemia patients.

Amlodipine: Can act as an antioxidant in patients with transfusion-dependent ß-thalassemia? A double-blind, controlled, crossover trial.

BACKGROUND AND AIM: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent ß-thalassemia (TDT) patients. METHODS: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, µmol/L), carbonyl (protein CO, µM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, µmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo. RESULTS: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). CONCLUSION: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.

Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines.

Background: High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning.Methods: This was a retrospective study from a single poison center. Cases were identified via the generic code "Calcium Antagonists" in which the therapy "High Dose Insulin/Glucose" was "performed, whether or not recommended" from 2019-2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia.Results: Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil n = 10, diltiazem n = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2-5; range 0-6) and 2 in the non-DHP group (IQR: 1-3; range 0-5; p = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0-2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min; p = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0; p = 0.009).Conclusions: Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.

A super-hydrophilic partially reduced graphene oxide membrane with improved stability and antibacterial properties.

In order to improve stability and antibacterial property, a novel super-hydrophilic partially reduced graphene oxide membrane was prepared by interfacial polymerization of piperazine and partially reduced graphene oxide as aqueous solution and trimesoyl chloride as organic solution. Fourier transform infrared spectroscopy, scanning electron microscope, and contact angle measurement were conducted to probe the morphology and properties of the membranes. The modified membrane possessed super-hydrophilicity, improved durability and swelling resistance. The optimized membrane had a molecular weight cut off of about 674 Da and possessed a pure water permeability of 49.86 L·m-2·h-1·MPa-1. The retention order of salts was Na2SO4 > MgSO4 > MgCl2 > Na2CO3 > CaCl2 > NaCl, while the rejection for four kinds of pharmaceuticals followed the order of ibuprofen (92%) > carbamazepine (87%) > amlodipine (80%) > atenolol (76%), indicating that the negatively charged membrane could improve the retention performance by the electrostatic repulsive effect. Moreover, the enhanced antibacterial performance of membrane attributed to the dual effects of the super-hydrophilicity and the tea polyphenols antibacterial material loading, which may alter the charge distribution on and within the membrane, leading to loss of cell viability.

Effect of 3, 2-Drug Combinations of Antihypertensive Therapies on Blood Pressure Variability in Black African Patients: Secondary Analyses of the CREOLE Trial.

BACKGROUND: The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine plus perindopril (CCB+ACE [angiotensin-converting enzyme]-inhibitor), and perindopril plus hydrochlorothiazide (ACE-inhibitor+thiazide) on blood pressure variability (V) are unknown. METHODS: We calculated the blood pressure variability (BPV) in 405 patients (130, 146, and 129 randomized to ACE-inhibitor+thiazide, CCB+thiazide, and CCB+ACE-inhibitor, respectively) who underwent ambulatory blood pressure monitoring after 6 months of treatment in the Comparisons of Three Combinations Therapies in Lowering Blood Pressure in Black Africans trial (CREOLE) of Black African patients. BPV was calculated using the SD of 30-minute interval values for 24-hour ambulatory BPs and for confirmation using the coefficient of variation. Linear mixed model regression was used to calculate mean differences in BPV between treatment arms. Within-clinic BPV was also calculated from the mean SD and coefficient of variation of 3 readings at clinic visits. RESULTS: Baseline distributions of age, sex, and blood pressure parameters were similar across treatment groups. Participants were predominately male (62.2%) with mean age 50.4 years. Those taking CCB+thiazide had significantly reduced ambulatory systolic and diastolic BPV compared with those taking ACE-inhibitor+thiazide. The CCB+thiazide and CCB+ACE-inhibitor groups showed similar BPV. Similar patterns of BPV were apparent among groups using within-clinic blood pressures and when assessed by coefficient of variation. CONCLUSIONS: Compared with CCB-containing combinations, ACE-inhibitor plus thiazide was associated with higher levels, generally significant, of ambulatory and within-clinic systolic and diastolic BPV. These results supplement the differential ambulatory blood pressure-lowering effects of these therapies in the CREOLE trial.

Single-Pass Albumin Dialysis as Rescue Therapy for Pediatric Calcium Channel Blocker Overdose.

Calcium channel blocker ingestions remain one of the leading causes of death related to cardiovascular medication ingestion in both adults and pediatric patients. We report a case of a 17-year-old, 103 kg female presenting after an intentional polypharmacy ingestion, including 500 to 550 mg of amlodipine. She presented with profound vasoplegia and cardiovascular collapse requiring high-dose inotropes and eventual life support with extracorporeal membrane oxygenation (ECMO). Current available treatments, designed for adults, including lipid emulsion and methylene blue, provided no sustained clinical improvement. This resulted in the initiation of single-pass albumin dialysis (SPAD). We aim to describe the clinical implications, amlodipine toxic dose effects, and clinical challenges associated with large pediatric patients and high-dose medications. We also discuss several challenges encountered related to dosing and concentration of medications, which led to fluid overload. Given the ongoing obesity epidemic, we routinely see pediatric patients of adult size. This will continue to challenge pediatric use of adult dosing and concentrations to avoid excessive fluid administration for high-dose medications, such as insulin and vasoactive agents. To our knowledge, this is the first successful case of using SPAD in conjunction with ECMO for salvage therapy after refractory life-threatening calcium channel blocker toxicity.

Eco-friendly spectrophotometric evaluation of triple-combination therapies in the treatment strategy of patients suffering from hypertension during coronavirus pandemic - Spectralprint recognition study.

Recent studies have reported that using certain antihypertensive therapies such as angiotensin II receptor blockers (ARBs) and calcium channel blocker (CCBs) is associated with reduction of fatal outcomes and improving clinical characteristics of patients suffering from hypertension during coronavirus pandemic. Thus, in the current work an effective, innovative and eco-friendly spectrophotometric manner namely, parent spectrum extraction (PSE)was established for evaluation of recommended triple antihypertensive combination therapies incorporate valsartan (VAL) as ARBs, amlodipine besylate as CCBs (AML) and hydrochlorothiazide (HCT)as diuretic into single-pill in challengeable ratio. PSE manner composed of two complementary steps, auxiliary resolution coupled with data analysis resolution(DAR)and it is characterized by resolving the spectral bands of the drugs and extraction of their discrete parent spectra (D0); accordingly, enabling determination of each analyte at its λmax. Auxiliary resolution of AML in triple mixture was applied to decrease complexity of overlapped spectra via constant multiplication (CM) followed by spectrum subtraction (SS) to obtain resolved mixture of VAL and HCT while data analysis resolution (DAR) of this binary mixture was applied via one of three novel methods namely, absorbance extraction (AE), peak-amplitude extraction (PE) and ratio extraction (RE) along with SS method. The proposed methods had analyzed VAL, AML and HCT in the range of 4.0-44.0 µg/mL, 4.0-40.0 µg/mL and 2.0-24.0 µg/mL, respectively with an excellent correlation coefficient (r ≥ 0.9999). Further, the proposed methods in PSR manner were validated as stated by ICH guidelines and it was found that accuracy and precision results are within the acceptable limit. The suggested procedures were effectively utilized for the concurrent quantification of VAL, AML and HCT in synthetic mixtures and tablets. The greenness of the proposed spectrophotometric methods was evaluated by National Environmental Methods Index (NEMI), the Analytical Eco-Scale, the Green Analytical Procedure Index (GAPI) and Analytical greenness metric (AGREE) where the four tools affirmed the eco-friendly nature of the proposed methods. A comparison between the outcomes of the studied methods with the official and reported ones was performed and no statistical difference was arisen between the methods regarding to accuracy and precision.The achieved results along with the simplicity, affordability and low-cost of the proposed methods recommended their appropriateness for the regular quality control examination and analysis of pure materials and pharmaceutical formulations as well as their applicability for the spectralprint recognition of the studied drugs.

Clinical assessment of levamlodipine besylate combination therapy for essential hypertension: A protocol for systematic review and meta-analysis.

BACKGROUND: Essential hypertension has been regarded a significant risk factor for cardiovascular disease across the globe, and a significant escapable causation of early death as well as morbidity in the U.S. When angiotensin II receptor blockers and calcium channel blockers are used to treat essential hypertension, most patients will have inadequate blood pressure management. As a result, including a diuretic in the regimen is necessary. The current study's aim is to investigate the effectiveness as well as safety of levamlodipine besylate combination therapy in treating essential hypertension at varying degrees of severity. METHODS: In establishing the effectiveness and safety of the mix of levamlodipine besylate and dihydropyridine for essential hypertension, the authors will conduct a systematic review and, where applicable, a meta-analysis of randomized controlled clinical trials. A total of 8 electronic databases will be used in the search, including 4 English databases (PubMed, Web of Science, EMBASE, and Cochrane Library) and 4 Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Literature database, Chinese Scientific Journal database, and WanFang database). All articles published in the databases will be considered between their inception and January 18, 2022. Only articles published in English or Mandarin Chinese will be picked. A group of writers will independently evaluate each reference to see if it is eligible and whether there are any duplicates. The same authors will do data extraction for all eligible studies and use the Cochrane risk of bias tool to evaluate the risk of bias in the trials chosen for inclusion. RESULTS: The analysis will evaluate the efficiency and level of safeness of levamlodipine besylate combined treatment for essential hypertension. CONCLUSIONS: Our systematic review will offer evidence for judging whether levamlodipine besylate combination therapy can be considered an effective intercession for essential hypertension. ETHICS AND DISSEMINATION: Ethical approval will not be required as no original data will be collected as part of this review. REGISTRATION NUMBER: DOI 10.17605/OSF.IO/H8ZR2.

Perindopril/Indapamide/Amlodipine in Hypertension: A Profile of Its Use.

The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension controlled with two-drug SPC of PER/IND + AML given as two separate pills at the same dose level. PER [an angiotensin-converting enzyme (ACE) inhibitor], IND (a thiazide-like diuretic) and AML (a calcium channel blocker) are well established antihypertensive agents, which have been available for a long time as monotherapies and dual SPCs and have complementary mechanisms of action. Once-daily PER/IND/AML provided effective BP control, with good tolerability, in patients with uncontrolled hypertension in clinical trials and in large observational prospective studies. The efficacy and tolerability of PER/IND/AML was similar to that of PER/IND + AML in a randomized clinical trial. The therapeutic effect of PER/IND/AML was associated with improved health-related quality of life. Thus, switching from the two-pill PER/IND + AML regimen to single-pill PER/IND/AML reduces pill burden and simplifies drug administration, which may improve adherence to treatment, leading to better BP control and clinical outcomes.

Approximately one-quarter of patients with hypertension require three antihypertensive agents to achieve BP control. However, complex treatment regimens and high pill burden reduce treatment adherence, which in turn leads to poor BP control. Perindopril (PER), indapamide (IND), amlodipine (AML) belong to the core drug classes for the treatment of hypertension. These drugs have been available for a long time as monotherapies and two-drug single-pill combinations. Once-daily PER/IND/AML provides very good BP control in patients with uncontrolled hypertension and is generally well tolerated. The single-pill PER/IND/AML has similar efficacy and tolerability to PER/IND + AML given as two separate pills. Therefore, switching from PER/IND + AML to PER/IND/AML reduces pill burden and simplifies the treatment regimen, which may improve adherence to treatment, leading to better BP control and clinical outcomes. Thus, PER/IND/AML is a valuable and convenient treatment option for patients with hypertension controlled with PER/IND + AML at the same dose level.

Efficacy and safety of Tengfu Jiangya tablet combined with valsartan/amlodipine in the treatment of stage 2 hypertension: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence rate of hypertension in the Chinese population is on the rise, and the control rate of hypertension is low. International guidelines, including the 2018 Chinese Guidelines for the Management of Hypertension, recommend optimized drug selection and combination therapy for patients with stage 2 hypertension and blood pressure ≥ 160/100 mmHg, including valsartan/amlodipine (Val/Aml). The traditional Chinese medicine (TCM) compound Tengfu Jiangya tablet (TJT; No. Z20110021, Shandong Provincial Food and Drug Administration) is prepared in the medical institution of Affiliated Hospital of Shandong University of Traditional Chinese Medicine. It is an effective compound preparation of TCM for the treatment of hypertension in the national clinical research base of TCM. The aim of this study was to evaluate the efficacy and safety of TJT combined with Val/Aml in the treatment of stage 2 hypertension with hyperactivity of liver yang. METHODS: This randomized double-blind, placebo-controlled, multicenter trial will be conducted with a total of 288 participants with stage 2 hypertension at seven clinical trial centers. The stratified random method will be used, and the subcenter will be taken as the stratification factor. Eligible patients will be randomly assigned (1:1) into groups receiving either TJT or placebo three times daily for 28 days, both combined with Val/Aml 80/5 mg. The primary efficacy endpoint is the reduction in the mean sitting systolic blood pressure (msSBP) and the mean sitting diastolic blood pressure (msDBP) from baseline to week 4. Adverse events and laboratory test results will be monitored throughout the trial. DISCUSSION: This is the first placebo-controlled randomized trial conducted to evaluate the efficacy and safety of a Chinese herbal extract combined with Val/Aml in patients with stage 2 hypertension. Our study may help to provide evidence-based recommendations of a complementary preventive measure for stage 2 hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030611 . Registered on 8 March 2020.

Comparison of the effects of calcium channel blockers plus iron chelation therapy versus chelation therapy only on iron overload in children and young adults with transfusion-dependent thalassemia: A randomized double-blind placebo-controlled trial.

BACKGROUND: Myocardial iron deposition is a significant cause of morbidity and mortality in patients with transfusion-dependent thalassemia (TDT). Amlodipine, L-type calcium channel blocker with regular chelation therapy may reduce myocardial iron overload. Lack of randomized trials prompted this study to assess the effect of calcium channel blocker (amlodipine) in combination with iron chelation therapy on iron overload in patients with TDT. METHODS: Sixty-four eligible patients were randomized to receive either amlodipine and chelation (group A) or chelation alone (group B) in double-blind placebo-controlled trial. Myocardial iron concentration (MIC) using T2* magnetic resonance imaging (MRI), liver iron concentration (LIC), left ventricular ejection fraction (LVEF), and serum ferritin were measured at baseline and 12 months. RESULTS: In the amlodipine group, mean cardiac T2* value significantly increased from 18.11 ± 8.47 to 22.15 ± 7.61 (p = .002) at 12 months, whereas in control group, there was a nonsignificant increase (p = .62) in cardiac T2* value from 19.50 ± 8.84 to 20.03 ± 9.07. There was a significant decrease in MRI-derived MIC in the amlodipine group compared to control group (1.93 ± 1.61 to 1.29 ± 0.90, p = .01). Changes in the LVEF (p = .45), MRI-derived LIC (p = .09), and serum ferritin (p = .81) were not significant between the two groups. CONCLUSION: Amlodipine is safe and when combined with chelation therapy appears to be more effective in reducing cardiac iron overload than chelation only in children and young adults with TDT.

Multi-organ dysfunction as a presentation of calcium channel blocker intoxication.

SummaryWe report the case of a 73-year-old woman who intentionally ingested 400 mg of amlodipine in a suicidal attempt who initially presented with hypotension which persisted despite aggressive therapy with fluid resuscitation, multiple pressor support, high-dose insulin therapy and calcium infusion. Her haemodynamic instability evolved to include bradycardia requiring atropine and transcutaneous pacing. Eventually she required salvage therapy with intravenous lipid emulsion (ILE) therapy . Despite all aggressive therapy, she developed multi-organ failure resulting in death. The literature on high-dose insulin euglycaemic therapy (HIET) and ILE therapy shows mixed results with some showing significant improvement in haemodynamic status. In our case, it had no significant positive impact on the outcome.

Refractory Shock from Amlodipine Overdose Overcomed with Hyperinsulinemia.

Intoxication from calcium channel blockers exhibits almost 50% mortality rates. Amlodipine is a long-acting dihydropyridine and inappropriate dosage poses a great threat for profound vasodilation, hypotension, and refractory vasopressor-resistant shock. A 72-year-old woman with unremarkable medical history presented to the emergency department due to amlodipine overdose after a suicide attempt attributed to COVID-19 pandemic severe anxiety disorder. Vital signs at presentation: heart rate 82 beats/ min, arterial pressure 72/55 mmHg, and oxygen saturation 98%. Resuscitation was initiated with intravenous infusion of normal saline 0,9%, noradrenaline, and calcium chloride, while activated charcoal was orally administrated; however, blood pressure remained at 70/45 mmHg. Abruptly, she experienced acute pulmonary edema and was finally intubated. We commenced high-dose insulin infusion with Dextrose 10% infusion to maintain euglycemic hyperinsulinemia. Hemodynamic improvement occurred after 30 min, systolic blood pressure raised to 95 mmHg, and decongestion was achieved with intravenous furosemide. Insulin effect was dose-dependent and patient's hemodynamic status improved after insulin uptitration. Eight days later, the patient was weaned from the mechanical ventilation and she was successfully discharged after 14 days. High-dose intravenous infusion of insulin up to 10 units/kg per hour appears as an inotropic agent possibly through alterations in myocardial metabolism of fatty acids and augmentation of insulin secretion and uptake. This regimen possibly exhibits additional vasotropic properties. We conclude that euglycemic hyperinsulinemia is a potentially advantageous treatment in CCB toxicity.

Pharmacokinetics of a Fixed-Dose Combination of Amlodipine/Losartan and Chlorthalidone Compared to Concurrent Administration of the Separate Components.

Hypertension is more effectively treated with coadministration of 2 or more antihypertensive drugs than with high-dose monotherapy. Therefore, calcium channel blockers, angiotensin II receptor blockers, and thiazides are coadministered to treat hypertension. The objective of this study was to compare the pharmacokinetic (PK) profiles of HCP1401, a fixed-dose combination of amlodipine 5 mg, losartan 100 mg, and chlorthalidone 25 mg, with the separate components (loose combination) of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg. A randomized, open-label, single-dose, 2-way crossover study was conducted. Blood samples for amlodipine and chlorthalidone were collected for up to 144 hours after dosing, whereas those for losartan were collected up to 48 hours after dosing. The PK parameters of these drugs were calculated using a noncompartmental method. Sixty subjects completed the study. The geometric mean ratios and 90% confidence intervals of maximum plasma concentration and area under the concentration-time curve to the last measurable point for amlodipine, losartan, and chlorthalidone were within the conventional bioequivalence range of 0.80 to 1.25. There were no clinically significant changes in safety assessments, and the treatments were well tolerated. The PK characteristics and tolerability profiles of a single oral FDC of amlodipine, losartan, and chlorthalidone were equivalent to those of individual tablets in a loose combination.