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Objective. This study was to study the efficacy of rosuvastatin, amlodipine, and aspirin in the treatment of hypertension with coronary heart disease and its effect on platelet aggregation. Methods. The participants included 60 patients with hypertension and coronary heart disease who were treated at our hospital between January 2020 and May 2021 and were randomly assigned to receive either rosuvastatin, amlodipine, and Ziyin Huoxue Recipe (observation group) or rosuvastatin, amlodipine, Ziyin Huoxue Recipe, and aspirin (experimental group), with 30 patients in each. Outcome measures included clinical effectiveness, blood pressure indicators, blood lipid indices, plasma viscosity, platelet aggregation, cardiac function, and adverse responses. Results. The clinical efficacy in the experimental group was significantly higher than that in the observation group (P < 0.05). The differences were found in blood pressure indices and blood lipid indices between the two groups before treatment (P > 0.05). However, after treatment, the blood pressure indices in the experimental group were significantly lower than those in the observation group (P < 0.05). After treatment, the blood lipid indices, plasma viscosity, and platelet aggregation in the experimental group were significantly lower than those in the observation group (P < 0.05). The left ventricular ejection fraction (LVEF) of patients in the experimental group after treatment was significantly higher than that of patients in the observation group (P < 0.05). There was no significant difference in the incidence of adverse reactions among patients in the two groups (P > 0.05). Conclusion. The clinical efficacy of rosuvastatin, amlodipine, and aspirin markedly reduces the blood pressure indices, blood lipid indices, plasma viscosity, and platelet aggregation of patients with hypertension and coronary heart disease, improves LVEF, and has a good safety profile. [ABSTRACT FROM AUTHOR]

Objective. To explore whether long-term administration of valsartan or amlodipine can improve vascular endothelial function and reduce the production of reactive oxygen species in patients with H-type hypertension, so as to provide a reference for clinical treatment. Methods. A total of 82 elderly patients with type H hypertension who were admitted to our hospital from March to August 2017 were selected as the research subjects. The study included a 4-week continuous irrigation period followed by a 24-week randomized treatment period. Forty patients in the valsartan group and 42 in the amlodipine group were treated with 5 mg amlodipine or 80 mg valsartan for 24 weeks. Clinical efficacy, 24 h mean DBP, SBP, and 24HSBP, DBP coefficient of variation, cardiac fatty acid-binding protein (H-FABP), vascular pseudohemophilia factor (VWF), nitric oxide (NO), endothelium-dependent vasodilation function (FMD), nonendothelium-dependent vasodilation function (NMD), malondialdehyde (MDA), GSH-Px, and SOD levels were observed. Results. The total effective rate was 80.0% (32/40) in the valsartan group and 85.71% (36/42) in the amlodipine group, and the difference was not statistically significant (P > 0.05). After 24 weeks of treatment, the 24 h mean SBP, SDP, 24HSBP, and DBP variation coefficients of the two groups were significantly decreased, and there was no statistical significance between the two groups (P > 0.05). After treatment, the values of H-FABP, VWF, NO, and MDA in both groups decreased compared with before treatment, while the values of FMD%, NMD%, SOD, and GSH-Px increased compared with before treatment (P > 0.05), and the levels of H-FABP, VWF, and NO in the valsartan group were lower than those in the amlodipine group. Meanwhile, FMD%, NMD%, SOD, and GSH-Px levels were higher than those in the amlodipine group (P > 0.05). Conclusion. Valsartan and amlodipine reduce blood pressure, improve vascular endothelial function, and inhibit oxidative stress in elderly patients with H-type hypertension on average. However, valsartan has a better effect on vascular endothelial dysfunction and oxidative stress in elderly patients with H-type hypertension. [ABSTRACT FROM AUTHOR]

Background. Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are challenging in humans. We applied a noninvasive forearm skin measurement of the 460-nm fluorescence specific for the reduced form of nicotinamide adenine dinucleotide (NADH) to study the 6-week effects of four different antihypertensive medications on mitochondrial function using the Flow-Mediated Skin Fluorescence (FMSF). Methods. In a prospective open-label study, we compared the long-term effects of a 6-week treatment with either amlodipine (5 mg), perindopril (5 mg), nebivolol (5 mg), or metoprolol (50 mg) on the dynamic flow-mediated changes in the skin NADH content in 76 patients (29 women) with untreated primary arterial hypertension (HA). Patients underwent 24-hour ambulatory blood pressure monitoring. To study mitochondrial function, the FMSF was measured at rest, during 100-second ischemia and postischemic reperfusion. The control group consisted of 18 healthy people (7 women). Results. There were no significant differences in the FMSF parameters between the control and the study group before medication. After the 6-week treatment, all drugs similarly reduced blood pressure. Neither amlodipine, perindopril, nor nebivolol changed the flow-mediated 460-nm skin fluorescence significantly. However, metoprolol raised this fluorescence at rest, during ischemia and reperfusion (P at most <0.05), indicating an increase in the total NADH skin content. Conclusion. Amlodipine, perindopril, and nebivolol appear neutral for the skin NADH content during the 6-week antihypertensive treatment. Similar treatment with metoprolol increased skin NADH at rest, during ischemia and reperfusion, probably due to an effect on microcirculation and altered mitochondrial function. Explanation of the potential mechanisms behind metoprolol influence on the skin NADH metabolism requires further investigation. [ABSTRACT FROM AUTHOR]

Introduction. Calcium channel blockers have pedal edema as one of the confining factors of treatment. A real-world study may help evident reality of the situation in regular Indian clinical practice. The aim of the study is to assess effectiveness and incidence of pedal edema in essential hypertensive patients treated with amlodipine or cilnidipine monotherapy. Methods. Retrospective EMR data of adult essential hypertensive patients, prescribed amlodipine (n = 800) or cilnidipine (n = 800) as monotherapy, were analyzed. Incidence of pedal edema from baseline visit was analyzed in terms of dose and duration of treatment. The changes in systolic (SBP) and diastolic blood pressure (DBP) from baseline and proportion of patients achieving target BP goals were assessed. Results. In amlodipine and cilnidipine groups, mean changes in SBP and DBP from baseline to end of the study period were 28.4 and 15.1 mmHg and 24.3 and 13.5 mmHg, respectively (p value <0.05). More than 50% of patients in both groups achieved BP goal at the end of the study (p value 0.266). In amlodipine group, total 23.9% reported pedal edema, while in cilnidipine, 27.6% (p value 0.0863). At the end of the study, 3.5% and 8.2% of patients remain with pedal edema, respectively, in both groups (p value <0.005). Conclusion. Amlodipine demonstrated greater BP reduction at a lower average dose, better efficacy, and tolerability in terms of pedal edema count as a lesser number of patients reported edema at the end of the study and a higher percentage of patients continued the prescribed baseline dosage regimen as compared to cilnidipine. Thus, the study established amlodipine as an effective and well-tolerated antihypertensive for Indians. [ABSTRACT FROM AUTHOR]

Background. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) ended in 2002, but it is important to study its long-term outcomes during the posttrial period by incorporating posttrial antihypertensive medication uses in the analysis. Purposes. The primary aim is to explore the patterns of antihypertensive medication use during the posttrial period from Medicare Part-D data over the 11-year period from 2007 to 2017. The secondary aim is to examine the potential effects of these posttrial antihypertensive medications on the observed mortality and morbidity benefits. Methods. This is a posttrial passive follow-up study of ALLHAT participants in 567 US centers in 1994–1998 with the last date of active in-trial follow-up on March 31, 2002, by linking with their Medicare and National Death Index data through 2017 among 8,007 subjects receiving antihypertensive drugs (3,637 for chlorthalidone, 2,189 for amlodipine, and 2,181 for lisinopril). Outcomes included posttrial antihypertensive drug use, all-cause mortality, and cardiovascular disease (CVD) mortality. Results. Of 8007 subjects, 3,637 participants were initially randomized to diuretic (chlorthalidone). The majority (67.9%) of them still received diuretics in 2007, and 52.7%, 47.2%, and 44.0% received β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers (CCBs), respectively. Compared to participants who received diuretic-based antihypertensives, those who received CCB had a nonsignificantly higher risk of all-cause mortality (1.17, 0.99–1.37), whereas those who received ACE/ARB (angiotensin receptor blockers) had a significantly higher risk of all-cause mortality (1.26, 1.09–1.45). For the combined fatal or nonfatal hospitalized events, the risk of CVD was significantly higher in patients receiving CCB (1.30, 1.04–1.61) and ACE/ARB (1.49, 1.22–1.81) as compared to patients receiving diuretics. Conclusion. After the conclusion of the ALLHAT, almost all patients switched to combination antihypertensive therapies, independently by the original drug class, and the combination therapies (mostly based on diuretics) reduced the incidence of major cardiovascular outcomes and mortality. [ABSTRACT FROM AUTHOR]

What is known and objective: Amlodipine overdose is common; however, the dose and timing of intravenous lipid emulsion (ILE) therapy as a management strategy remain debatable. Case description: A 73‐year‐old man received a single bolus (1.5 mL/kg) of ILE therapy following massive ingestion of multiple drugs, including amlodipine. After approximately 20 hours of ILE therapy, the serum amlodipine level that had decreased from 90.2 to 49.9 ng/mL increased to 70.8 ng/mL. What is new and conclusion: A single bolus (1.5 mL/kg) of ILE therapy is probably insufficient to completely capture and partition serum amlodipine following amlodipine overdose. [ABSTRACT FROM AUTHOR]

Background. Hypertension (HTN) is the leading risk factor for cardiovascular mortality globally. The WHO estimates a 60% increase in Asian HTN patients between 2000 and 2025. Numerous studies have compared safety and efficacy between antihypertensive classes, but in-class comparisons of angiotensin II receptor blockers (ARBs) in combination therapy (CT) (fixed-dose combination or dual combination) with a calcium channel blocker (CCB) are lacking in Asia. Objective. To compare the efficacy and safety of the various ARB-amlodipine CTs and amlodipine (AML) monotherapy for treatment of HTN in Asian population. Methods. A systematic literature review sourced Asian randomized controlled trials (RCTs) from PubMed and Cochrane Libraries to inform a network meta-analysis (NMA). We considered the ARB-AML CT. The primary efficacy and safety endpoints were short-term (8–12 weeks) treatment response and treatment-emergent adverse events (TEAEs), respectively. AML monotherapy was used as a comparator to allow for indirect treatment effect estimation in the absence of direct RCTs evidence comparing the different ARB-AML CTs. Results. The analysis included 1198 Asian HTN patients from seven studies involving six ARB-AML CTs: azilsartan (AZL), candesartan (CAN), fimasartan (FIM), losartan (LOS), olmesartan (OLM), and telmisartan (TEL). Compared to AML monotherapy, CT of AZL-AML had five times greater odds of prompting a treatment response (OR 5.2, 95% CI: 2.5, 11.2), while CAN-AML had 3.9 (95% CI: 2.5, 6.4), FIM-AML had 3.4 (95% CI: 1.4, 8.5), TEL-AML had 3.3 (95% CI: 1.6, 7.1), OLM-AML had 2.7 (95% CI: 1.6, 5.0), and LOS-AML had 2.0 (95% CI: 0.6, 7.3). All ARB-AML CTs had safety profiles comparable to AML monotherapy except TEL-AML, which had significantly lower odds of TEAEs (0.26 (95% CI: 0.087, 0.70)). Conclusion. This study suggests that all ARB-AML CTs compared favorably to AML monotherapy regarding short-term treatment response in uncomplicated HTN patients of Asian origin. AZL-AML prompted the most favorable treatment response. Safety profiles among the ARB-AML CTs were largely comparable. Due to the limited study size and small number of trials (direct evidence), our findings should best be interpreted as an exploratory effort importance to inform future research direction. [ABSTRACT FROM AUTHOR]

Sulfonate esters have been recognized as potential genotoxic impurities (PGIs) in pharmaceuticals. An LC-MS/MS method was developed and validated for the simultaneous determination of 15 sulfonate esters, including methyl, ethyl, propyl, isopropyl, and n-butyl esters of methanesulfonate, benzenesulfonate, and p-toluenesulfonate in drug products. The method utilized atmospheric pressure chemical ionization (APCI) in multiple reaction monitoring (MRM) mode for the quantitation of impurities. The method employed an ODS column as the stationary phase and water-acetonitrile as the solvents for gradient elution without derivatization steps. The method was specific, linear, accurate, precise, and robust. Recoveries of the sulfonic esters from three drug matrices were observed in the range of 91.6∼109.0% with an RSD of not greater than 17.9% at the concentration of the LOQ and in the range of 90.4%∼105.2% with an RSD of not greater than 7.1% at the concentration of 50 ng/mL for the methanesulfonates and 10 ng/mL for the benzenesulfonates and p-toluenesulfonates. The LOD was not greater than 15 ng/mL, 2 ng/mL, and 1 ng/mL for the methanesulfonate, benzenesulfonate, and p-toluenesulfonate esters, respectively. This method was sufficiently sensitive to detect the 15 PGIs in the phentolamine mesylate tablet, amlodipine besylate tablet, and tosufloxacin tosylate tablet. This analytical method is a direct, specific, rapid, and accurate quality control tool for the determination of the 15 sulfonate esters that are most likely to exist in drug products. [ABSTRACT FROM AUTHOR]

In this work, a new solution has been found for selecting the approximate initial value of concentration (by means of the classical least squares) and variance (calculated by the Horwitz equation) for the Kalman filter algorithm. With this solution, the Kalman method is less error-prone and has a better repeatability than the least squares method when using the full spectrum. A protocol for simultaneous determination of amlodipine (AML), hydrochlorothiazide (HYD), and valsartan (VAL) in pharmaceutical products was developed based on the spectrophotometry-chemometric method using full spectrum measurement in combination with the Kalman filter algorithm written in Microsoft Excel 2016 and Visual Basic for Applications (VBA). The method was validated on the Exforge HCT tablets with good repeatability (RSD) (varied from 2.2% to 2.3% (n = 3) for all the three studied compounds) and good recovery (90.0%–94.0% for AML, 90.3%–94.5% for HYD, and 98.5%–103.1% for VAL (n = 3)). The results were in good agreement with the measurements achieved from the high-performance liquid chromatography (HPLC) method. [ABSTRACT FROM AUTHOR]

Historically, traditional herbal medicines (THMs) have been the conventional treatment strategy in the Korean medical system for treating many diseases. However, THMs have rarely been used to treat hypertension, and moreover few studies have investigated the interaction of blood pressure with the coadministration of synthetic antihypertensives. We aimed to evaluate the vasorelaxant and hypotensive effects of the traditional herbal prescription Cheonwangbosimdan (CWBSD; “Tianwangbuxindan” in Chinese) and the combination of CWBSD with amlodipine. CWBSD was extracted with distilled water at 100°C for 2 h. To investigate vasorelaxant activities, CWBSD with amlodipine (10 μg/ml) was added cumulatively (10–1,000 μg/ml) to isolated rat aortic rings precontracted using phenylephrine or potassium chloride in organ chambers. To investigate hypotensive effects, CWBSD (2,476 mg/kg) was orally administered with or without amlodipine (5 mg/kg) to spontaneously hypertensive rats (SHRs). CWBSD increased the relaxation of rat aortic rings induced by amlodipine (P < 0.01). In vivo, CWBSD coadministration with amlodipine also significantly decreased the blood pressure of SHRs compared to the amlodipine-treated group. These results suggested that CWBSD could be a useful herbal prescription to treat hypertension and we recommend establishing guidelines for the use of herbal medicines in conjunction with antihypertensive drugs, including amlodipine. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. Methods: Events reported to the FDA Adverse Event Reporting System from the years 2004‐2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow‐Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. Results and discussion: Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P < .01). What is new and conclusion: Inconsistent reporting patterns were observed more between brand and generic compared with AG and generic. Use of AGs as a control for perception biases against generics is useful, but this approach can be limited by small AG report numbers. Requiring the manufacturer name to be printed on the prescription bottle or packaging could improve the accuracy of assignment for products being reported. [ABSTRACT FROM AUTHOR]

Calcium channel blockers are among the first-line drugs for treatment of hypertension (HTN). S-amlodipine (S-AM), an S-enantiomer of amlodipine, is available in India and in other countries like China, Korea, Russia, Ukraine, and Nepal. Being clinically researched for nearly two decades, we performed in-depth review of S-AM. This review discusses clinical evidence from total 42 studies (26 randomized controlled trials, 14 observational studies, and 2 meta-analyses) corroborating over 7400 patients treated with S-AM. Efficacy and safety of S-AM in HTN in comparison to racemic amlodipine, used as monotherapy and in combination with other antihypertensives, efficacy in angina, and pleiotropic benefits with S-AM, are discussed in this review. [ABSTRACT FROM AUTHOR]

We have analysed the database of 1,595 consecutive patients visiting our department of cardiology and internal medicine clinic in 2005–2014. The analysis included 13,990 visit records, and the average number of visits per patient was 8.5 ± 7.0. Our goals were to evaluate the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in patients with metabolic syndrome and/or diabetes mellitus. The final number of patients for analysis who fulfilled the inclusion criteria for interpenetration of both diagnostic circles was 570. Results. 15% of patients were treated using hypertension monotherapy, 70% of patients were treated using 2- to 4-drug combination therapy, and 15% of patients were treated using 5- to 6-drug combination. The drugs used most frequently were perindopril (perin), nitrendipine (nitre), amlodipine (amlo), telmisartan (telmi), hydrochlorothiazide (hydro), rilmenidine, and nebivolol (used in >100 patients). The most significant decrease of sBP was associated with treatment by nitre, hydro, telmi, and urapidil (>19 mmHg). The most significant decrease of dBP was associated with treatment by nitre, hydro, telmi, and verapamil (>10 mmHg). The most significant decrease of both sBP and dBP was associated with treatment using 3-drug combination of telmi + hydro + spironolactone (41 and 16 mmHg, resp.), telmi + hydro + nitre (34 and 15 mmHg, resp.), and telmi + hydro + urapidil (34 and 15 mmHg, resp.). At the last visit, 281 out of 413 patients at the first visit had sBP >140 mmHg (68%); that is, sBP control was 32%. At the last visit, 76 patients out of 217 at the first visit had dBP >90 mmHg (35%); that is, dBP control was 65%. Therapeutic inertia was calculated by evaluating the proportion of visits at which sBP was above the target for eligible visits minus the proportion of visits where the change was made in antihypertensive treatment (AHT), either medication type or dose, over the number of eligible visits, with the resultant value multiplied by the mean of the difference between the actual sBP and the target value at clinic visits. TIQ was counted at first 200 consecutive patients, and the average value was 57.30 ± 147.20. Conclusion. The study presents the real-life data concerning the difficulties in hypertension treatment in patients with concomitant metabolic syndrome and/or type 2 diabetes mellitus. sBP was controlled at 32% patients only. The study results allow evaluating the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in these patients. [ABSTRACT FROM AUTHOR]

What is known and objective Studies indicate that there is an increased serum concentration of amlodipine (a calcium channel blocker used to treat hypertension and angina) in patients having mutant multidrug resistance 1 ( MDR1) gene. Hence, genetic factors may play a very significant role in amlodipine-induced complications including gingival enlargement. Case description Three patients with amlodipine-induced gingival enlargement showed improvement following drug substitution of amlodipine with enalapril (an angiotensin-converting enzyme inhibitor) and non-invasive periodontal therapy. Using allele-specific polymerase chain reaction, single nucleotide polymorphism of MDR1 gene of heterozygous mutant type ( CT genotype) was identified in all three cases. What is new and conclusion Drug-induced complications can potentially be a result of genetic factors, in combination with various local and systemic factors. Identifying genetic polymorphisms early might help predict adverse reactions and determine prognosis. [ABSTRACT FROM AUTHOR]

A study was carried out to investigate compatibility of amlodipine besylate and olmesartan medoxomil with a variety of pharmaceutical excipients. Both drugs are antihypertensive agents that can be administered alone, in monotherapy, or in pharmaceutical association. The studies were performed using binary and ternary mixtures, and samples were stored for 3 and 6 months at 40°C under 75% relative humidity and dry conditions. For this study, a method based on high-performance liquid chromatography (HPLC) was developed and validated for the simultaneous determination of amlodipine besylate and olmesartan medoxomil in samples from pharmaceutical preformulation studies using diode array detector (DAD) and charged aerosol detector (CAD). The runtime per sample was 10 min with retention time of 7.926 min and 4.408 min for amlodipine and olmesartan, respectively. The validation was performed according to ICH guidelines. The calibration curve presents linear dynamic range from 12 to 250 μg mL−1 for amlodipine and from 25 to 500 μg mL−1 for olmesartan with coefficient of determination (R2 ≥ 0.9908) while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.0%. The excipients such as corn starch, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, talc, polyvinylpyrrolidone, lactose monohydrate, and polyethylene glycol showed potential incompatibilities after accelerated stability testing. [ABSTRACT FROM AUTHOR]

REFERENCES 1 Fu J., Wang T., Li B., Zhao N. The Efficacy of Rosuvastatin, Amlodipine, and Aspirin in the Treatment of Hypertension with Coronary Heart Disease and Its Effect on Platelet Aggregation. This article has been retracted by Hindawi following an investigation undertaken by the publisher [[1]]. [Extracted from the article]

Atorvastatin and ticagrelor combination is a widely accepted therapy for secondary prevention of ischaemic heart disease. However, rhabdomyolysis is a well-known rare side effect of statins which should be considered when treatments are combined with cytochrome P450 3A4 enzyme inhibitors. We report a case of atorvastatin and ticagrelor associated severe rhabdomyolysis that progressed to multiorgan failure requiring renal replacement therapy, inotropes, intubation, and mechanical ventilation. Despite withdrawal of the precipitating cause and the supportive measures including renal replacement therapy, creatinine kinase increased due to ongoing rhabdomyolysis rapidly progressing to upper and lower limbs weakness. A muscle biopsy was performed to exclude myositis which confirmed extensive myonecrosis, consistent with statin associated rhabdomyolysis. After a prolonged ventilatory course in the intensive care unit, patient’s condition improved with recovery from renal and liver dysfunction. The patient slowly regained her upper and lower limb function; she was successfully weaned off the ventilator and was discharged for rehabilitation. To our knowledge, this is a second case of statin associated rhabdomyolysis due to interaction between atorvastatin and ticagrelor. However, our case differed in that the patient was also on amlodipine, which is considered to be a weak cytochrome P450 3A4 inhibitor and may have further potentiated myotoxicity. [ABSTRACT FROM AUTHOR]

Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI) through improving bone marrow endothelial progenitor cell (EPC) mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1), amlodipine (2.5 mgkg−1 day−1), or vehicle by gavage (n=20 per group). Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5). Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension guidelines recommend fixed-dose combinations for enhanced blood pressure (BP) reduction and compliance. The objective of this study was to assess the effectiveness and safety of fixed-dose perindopril/amlodipine combination in reducing and controlling BP in Greek hypertensive patients, as well as the effect of baseline BP and added cardiovascular risk on BP reduction.Methods: This 6-month prospective observational study included male or female patients ⩾18 years with essential hypertension prescribed fixed-dose combination perindopril/amlodipine. BP was measured at baseline and 3 and 6 months. Baseline cardiovascular risk and treatment compliance were also assessed.Results: In 2231 per protocol patients, mean systolic BP decreased from 157.0±15.4 mm Hg to 129.0±7.9 mm Hg after 6 months, and diastolic BP from 91.5±10.1 to 78.8±6.7 mm Hg (both p < 0.001). BP control was achieved in 84.8% at 6 months. Patients with higher baseline added cardiovascular risk or BP had greater BP reduction (p < 0.001). Compliance was good (97.1% took treatment "every day" or "quite often") and few (n = 27; 1.2%) discontinued treatment prematurely due to adverse events.Conclusions: Fixed-dose perindopril/amlodipine safely and effectively reduced high BP in real-life practice, achieving BP control in most patients. About half of Greek hypertensive patients have high/very high added cardiovascular risk. [ABSTRACT FROM AUTHOR]

Amlodipine overdose can be life-threatening when manifesting as noncardiogenic pulmonary edema. Treatment remains challenging. We describe a case of noncardiogenic pulmonary edema without refractory hypotension and bradycardia after ingestion of 500 milligram amlodipine with suicidal intent. Mechanical ventilation, dexamethasone, atrovent HFA (ipratropium), pulmicort inhalation, and antibiotic therapy were used for the management. Length of hospital stay was 11 days. The patient was discharged with full recovery. [ABSTRACT FROM AUTHOR]

Background. Brain-derived neurotrophic factor (BDNF) is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs) and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications. Methods. In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels. Results. Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (r=-0.264, P=0.021) but not in the 77 subjects treated with benazepril/amlodipine (r=-0.025, P=0.862). The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR (-8.8±14.9 mL/min/1.73 m2; P<0.001). Multivariate regression analysis revealed that increased serum BDNF represents an independent factor for reduced eGFR (95% confidence interval between −0.887 and −0.076, P=0.020). Conclusions. Increased serum BDNF is associated with reduced eGFR in type 2 diabetic subjects treated with valsartan/hydrochlorothiazide but not with amlodipine/benazepril. [ABSTRACT FROM AUTHOR]

Simvastatin is among the most commonly used prescription medications for cholesterol reduction and the most common statin-related adverse drug reaction is skeletal muscle toxicity. Multiple factors have been shown to influence simvastatin-induced myopathy. In addition to age, gender, ethnicity, genetic predisposition, and dose, drug-drug interactions play a major role. This is particularly true for drugs that are extensively metabolized by cytochrome P450 (CYP)3A4. We describe a particularly severe case of rhabdomyolysis after the introduction of ciprofloxacin, a weak CYP3A4 inhibitor, in a patient who previously tolerated the simvastatin-amlodipine combination. [ABSTRACT FROM AUTHOR]

Amlodipine is a third generation dihydropyridine calcium channel blocker that is frequently used in therapy of hypertension. Among many side effects, amlodipine has been found associated with gingival overgrowth (GO) which usually occurs within the first three months of starting therapy at a dose of 10 mg/day. However, there are very few reports on amlodipine-induced gingival overgrowth (AIGO) at a lower dose (5 mg/day) and only after short term administration. A 64-year-old male patient with hypertension, who received amlodipine (5 mg/day) for four years, sought medical attention at the Department of Periodontology and Oral Medicine, Institute of Dentistry, Banja Luka, Bosnia and Herzegovina. The patient complained of masticatory problems due to extensive maxillary GO along with pain, bleeding, and foul odor. The clinical and the histological evidences were consistent with AIGO. The first line treatment consisted of the amlodipine substitution (amlodipine was replaced with enalapril, 5 mg/day) and the scaling and root planning/SRP. At one-month follow-up, drug replacement and SRP resulted in some reduction of the inflammation and significant reduction of symptoms. Further, gingivectomy/gingivoplasty helped overcome the effect of these drugs. The possibility of AIGO should be considered for a lower dose, as well as a late presentation. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of the telmisartan plus amlodipine (T/A) single-pill combination (SPC) in Asian patients with hypertension whose blood pressure (BP) was not adequately controlled on either monotherapy or on low-dose combination therapy. Patients and Methods. Data are presented from five Boehringer Ingelheim-sponsored phase 3, double-blind, 8-week, studies: two studies in nonresponders to amlodipine (data pooled for amlodipine), two studies on nonresponders to telmisartan (pooled data), and one on nonresponders to low-dose T/A SPC. Results. After 8 weeks' treatment, mean reductions from the reference baseline in diastolic BP (DBP; primary endpoint), systolic BP (SBP), and SBP, DBP goal, and response rates were higher with the T/A SPC than respective monotherapies. The T80/A5 SPC resulted in greater reductions in DBP and SBP, and higher DBP goal and response rate than the low-dose T40/A5 SPC. Peripheral edema incidence was low (amlodipine 0.5%, telmisartan 0.0%, and T/A SPC 0.7%). Discussion and Conclusion. In Asian patients whose BP is not adequately controlled with telmisartan or amlodipine monotherapy, T/A SPC treatment results in greater BP reduction, and higher DBP and SBP goal and response rates. The safety and tolerability of the T/A SPC are comparable to those of the respective monotherapies and consistent with those reported in previous studies. [ABSTRACT FROM AUTHOR]

A novel, rapid, accurate, sensitive, precise, and stability-indicating reverse-phase ultra-performance liquid chromatographic (RPUPLC) method was developed and validated for determination of related substances of S(-)Amlodipine and S(-)Metoprolol Succinate in fixed dose combination tablet dosage form. The chromatographic separation was achieved with the use of Acquity UPLC HSS T3,1.8 μm, 2.1 x 100 mm analytical column at 45°C employing a gradient elution. Mobile phase consisting of mobile phase-A (solution containing 5.0 gm of sodium dihydrogen phosphate monohydrate per liter of water and Acetonitrile in the ratio of 95: 5) and mobile phase-B (Acetonitrile) was used at a flow rate of 0.5 mL min-1 with injection volume of 10 μL and the detection was done at 232 nm using UV detector. The retention times of S(-)Metoprolol Succinate and S(-)Amlodipine were found to be 2.8 minutes and 8.1 minutes, respectively. During method validation all the parameters were evaluated as per ICH guidelines, which remained well within acceptable limits. This method can be used for the estimation of related substances of S(-)Amlodipine and S(-)Metoprolol Succinate in fixed dose combination tablet dosage form. [ABSTRACT FROM AUTHOR]

The present study describes the stability indicating RP-HPLC method for simultaneous estimation of aliskiren hemifumarate and amlodipine besylate in pharmaceutical dosage forms. The proposed RP-HPLC method was developed by using waters 2695 separation module equipped with PDA detector and chromatographic separation was carried on C-8 Inertsil ODS (150 x 4.6 mm, 5 $ column at a flow rate of 1 mL/min and the run time is 10 min. The mobile phase consisted of phosphate buffer and acetonitrile in the ratio of 40: 60% v/v and pH was adjusted to 3 with orthophosphoric acid and eluents were scanned using PDA detector at 237 nm. The retention time of aliskiren and amlodipine was found to be 3.98 and 5.14 min, respectively. A linearity response was observed in the concentration range of 30-225 μg/mL for aliskiren and 2-15 μg/mL for amlodipine, respectively. Limit of detection and limit of quantification for aliskiren are 0.161 μg/mL and 0.489 μg/mL and for amlodipine are 0.133 μg/mL and 0.404 μg/mL, respectively. The stability indicating method was developed by subjecting the drugs to stress conditions such as acid and base hydrolysis, oxidation, and photo- and thermal degradation and the degraded products formed were resolved successfully from the samples. [ABSTRACT FROM AUTHOR]

What is known and Objective: To evaluate the effects of an olmesartan/amlodipine single pill combination compared with olmesartan or amlodipine monotherapies on blood pressure control, lipid profile, insulin sensitivity and some adipocytokines levels. Methods: Two hundred and seventy-six patients were enroled in the study and were randomly assigned to take olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20 mg/5 mg for 12 months. We evaluated at the baseline, and after 6 and 12 months: body weight, body mass index, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), resistin (r), interleukin-1β (IL-1β) and interleukin-5 (IL-5). At the baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity ( M value). Results and Discussion: There was a similar decrease in SBP and DBP after 6 and 12 months in all groups, even if olmesartan/amlodipine combination gave a major decrease in SBP and DPB compared with amlodipine and olmesartan monotherapies. Olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy. Olmesartan/amlodipine combination decreased FPI and HOMA index and increased M value both compared with baseline and compared with olmesartan and amlodipine monotherapies. Both olmesartan and olmesartan/amlodipine increased ADN and reduced r, without significant differences between the two groups. Regarding interleukins, no differences emerged in group to group comparison. What is new and Conclusion: Olmesartan/amlodipine combination resulted more effective than olmesartan and amlodipine monotherapies in reducing blood pressure, and in increasing insulin sensitivity parameters, but not resulted more effective in improving adipocytokines and interleukins levels analysed, compared with amlodipine or olmesartan monotherapy in hypertensive patients in this double-blind, randomized clinical trial. [ABSTRACT FROM AUTHOR]

A new, simple and specific spectrophotometric method was developed and validated in accordance with ICH guidelines for the simultaneous estimation of Amlodipine (AML), Valsartan (VAL), and Hydrochlorothiazide (HCT) in their ternary mixture. In this method three techniques were used, namely, direct spectrophotometry, ratio subtraction, and isoabsorptive point. Amlodipine (AML) was first determined by direct spectrophotometry and then ratio subtraction was applied to remove the AML spectrum from the mixture spectrum. Hydrochlorothiazide (HCT) could then be determined directly without interference from Valsartan (VAL) which could be determined using the isoabsorptive point theory. The calibration curve is linear over the concentration ranges of 4-32, 4-44 and 6-20 μg/mL for AML, VAL, and HCT, respectively. This method was tested by analyzing synthetic mixtures of the above drugs and was successfully applied to commercial pharmaceutical preparation of the drugs, where the standard deviation is < 2 in the assay of raw materials and tablets. The method was validated according to the ICH guidelines and accuracy, precision, repeatability, and robustness were found to be within the acceptable limits. [ABSTRACT FROM AUTHOR]

A rapid, precise, sensitive, economical, and validated high performance thin layer chromatographic method is developed for simultaneous quantification of olmesartan medoxomil and hydrochlorothiazide in combined tablet dosage form. The method used amlodipine as internal standard (IS). Chromatographic separations were achieved on silica gel 60 F254 plates using toluene-methanol-ethyl acetate-acetone (2.5 : 1 : 0.5 : 2, v/v/v/v) as mobile phase. Densitometric analysis was carried out in the reflectance mode at 258 nm. Calibration curves were linear over a range of 80-480 ng/band for olmesartanmedoxomil and 25-150 ng/band for hydrochlorothiazide. The detection and quantification limits were found to be 18.12 and 56.35 ng/band for olmesartan medoxomil and 6.31 and 18.56 ng/band for hydrochlorothiazide, respectively. Intra- and interassay precision provided relative standard deviations lower than 2% for both analytes. Recovery from 99.60 to 101.22% for olmesartan medoxomil and 98.30 to 99.32% for hydrochlorothiazide show good accuracy. Both the drugs were also subjected to acid, alkali, oxidation, heat, and photodegradation studies. The degradation products obtained were well resolved from pure drugs with significantly different Rf values. As the method could effectively separate the drugs from their degradation products, it can be used for stability-indicating analysis. Validation of the method was carried out as per international conference on harmonization (ICH) guidelines. [ABSTRACT FROM AUTHOR]

A simple, rapid, and selective HPLC-UV method was developed for the determination of antihypertensive drug substances: amlodipine besilat (AML), olmesartan medoxomil (OLM), valsartan (VAL), and hydrochlorothiazide (HCT) in pharmaceuticals and plasma. These substances are mostly used as combinations. The combinations are found in various forms, especially in current pharmaceuticals as threesome components: OLM, AML, and HCT (combination I) and AML, VAL, and HCT (combination II). The separation was achieved by using an RP-CN column, and acetonitrile-methanol-10mmol orthophosphoric acid pH 2.5 (7 : 13 : 80, v/v/v) was used as a mobile phase; the detector wavelength was set at 235 nm. The linear ranges were found as 0.1-18.5 µg/mL, 0.4-25.6 µg/mL, 0.3-15.5 µg/mL, and 0.3-22 µg/mL for AML, OLM, VAL, and HCT, respectively. In order to check the selectivity of the method for pharmaceutical preparations, forced degradation studies were carried out. According to the validation studies, the developed method was found to be reproducible and accurate as shown by RSD ≤6.1%, 5.7%, 6.9%, and 4.6% and relative mean error (RME) ≤10.6%, 5.8%, 6.5%, and 6.8% for AML, OLM, VAL, and HCT, respectively. Consequently, the method was applied to the analysis of tablets and plasma of the patients using drugs including those substances. [ABSTRACT FROM AUTHOR]

Hypertensive patients unable to reach blood pressure (BP) targets with antihypertensive monotherapy may be switched to a combination of two medications with complementary modes of action for improved treatment response. This post hoc analysis pools data from 2812 patients, 1891 of whom were not at goal (diastolic BP [DBP] <90mmHg) with amlodipine 5mg (A5) monotherapy who subsequently switched to telmisartan 40 or 80mg (T80)/A5 single-pill combination (SPC) or amlodipine 10mg (A10) monotherapy, and considers an additional 921 patients, 616 of whom were not at goal with A10 monotherapy who switched to telmisartan/amlodipine SPC. Patients switched to telmisartan/amlodipine SPC achieved significantly greater BP reductions compared with continued monotherapy (P < 0.0001) with reductions of −15.2/−10.9mmHg seen with T80/A5 after 8 weeks in patients switched from A5. BP goal (<140/90mmHg), systolic BP goal (<140mmHg), and DBP goal (<90mmHg) were reached by significantly more patients with telmisartan/amlodipine than with monotherapy (P < 0.0001 for all comparisons; 56.1%, 69.7%, and 66.9%, resp., in patients who switched from A5 to T80/A5). Early use of such combination therapy should be considered to quickly reach BP targets, particularly in patients with added risk. [ABSTRACT FROM AUTHOR]

Sympathetic hyperactivity may be involved in primary hypertension. The purpose of this study was to evaluate both sympathetic and vagal activity responses in patients receiving amlodipine as antihypertensive agent. Patients and Methods. This prospective study included a group of primary hypertensive patients (N = 32, mean age 54.6 ± 7.6 years). The cardiovascular autonomic tests performed in this group, before and after 3months of daily oral administration of amlodipine, included deep breathing, hand-grip, andmental stress tests. Statistical analysis was done using the Student's t-test. Results. Cardiovascular autonomic reflexes responses before and after 3months of amlodipine oral administration were as follows: the mental stress test stimulationmethod produced a central alpha adrenergic response of 23.9±8.7% versus 11.2±2.0% (P < 0.05), a central beta sympathetic response of 16.7±9.2% versus 10.4±1.3% (P < 0.05), a blood pressure increase in response to hand grip test of 20.5±7.3% versus 10.7±2.4% (P < 0.05), vagal response to deep breathing test was 21.2±6.5% versus 30.8±2.9%, (P < 0.05). Conclusion. The results attest that amlodipine may have an anti-sympathetic effect. [ABSTRACT FROM AUTHOR]

A Simple high-performance thin layer chromatography (HPTLC) method for separation and quantitative analysis of losartan potassium, amlodipine, and hydrochlorothiazide in bulk and in pharmaceutical formulations has been established and validated. After extraction with methanol, sample and standard solutions were applied to silica gel plates and developed with chloroform:methanol : acetone : formic acid 7.5 : 1.3 : 0.5 : 0.03 (v/v/v/v) asmobile phase. Zones were scanned densitometrically at 254 nm. The Rf values of amlodipine besylate, hydrochlorothiazide, and losartan potassium were 0.35, 0.57, and 0.74, respectively. Calibration plots were linear in the ranges 500-3000 ng per spot for losartan potassium, amlodipine and hydrochlorothiazide, the correlation coefficients, r, were 0.998, 0.998, and 0.999, respectively. The suitability of this method for quantitative determination of these compounds was by validation in accordance with the requirements of pharmaceutical regulatory standards. The method can be used for routine analysis of these drugs in bulk and in formulation. [ABSTRACT FROM AUTHOR]

Resolution of binary mixture of atorvastatin (ATV) and amlodipine (AML) with minimum sample pretreatment and without analyte separation has been successfully achieved using a rapid method based on partial least square analysis of UV-spectral data. Multivariate calibration modeling procedures, traditional partial least squares (PLS-2), interval partial least squares (iPLS) and synergy partial least squares (siPLS), were applied to select a spectral range that provided the lowest prediction error in comparison to the full-spectrum model. The simultaneous determination of both analytes was possible by PLS processing of sample absorbance between 220-425 nm. The correlation coefficients (R) and root mean squared error of cross validation (RMSECV) for ATV and AML in synthetic mixture were 0.9991, 0.9958 and 0.4538, 0.2411 in best siPLS models respectively. The optimized method has been used for determination of ATV and AML in amostatin commercial tablets. The proposed method are simple, fast, inexpensive and do not need any separation or preparation methods. [ABSTRACT FROM AUTHOR]

It has been proved that cilnidipine has N-type calcium channels inhibitory activity as well as L-type calcium channels and inhibits excessive release of norepinephrine from the sympathetic nerve ending. This study was undertaken to compare the efficacy of amlodipine (an inhibitor of L-type calcium channels) and cilnidipine (an inhibitor of both L-type and N-type calcium channels) in patients with hypertension and type II diabetes mellitus. Seventy-seven hypertensive patients were divided into two groups according to presence/absence of type II diabetes mellitus. In these two groups of patients, the effects of amlodipine and cilnidipine on glucose and lipid metabolism and renal function were compared. As for glucose and lipid metabolism, homeostasis model assessment insulin resistance (HOMA-R) level in the non-diabetic group and triglyceride in the diabetes group were significantly lower with cilnidipine than with amlodipine. As regards renal function in the diabetic group, estimated glomerular filtration rate (eGFR) was significantly higher and urinary albumin/creatinine ratio was significantly lower with cilnidipine than with amlodipine. Cilnidipine which inhibits N-type calcium channels is more useful for patients with hypertension and diabetes mellitus from its effects on glucose and lipid metabolism and renal function. [ABSTRACT FROM AUTHOR]

Introduction. Overdose with the calcium channel blocker amlodipine can cause profound hypotension that may be exacerbated by the concurrent ingestion of an angiotensin II receptor antagonist. Bestmanagement of such overdoses is uncertain although the use of hyperinsulinaemia-euglycaemia (HIE) has been recommended. Case report. We report a case of mixed amlodipine and losartan overdose in a 50-year-old lady. Severe hypotension was resistant to conventional vasopressors and high-dose insulin/euglycaemia, but did respond to a metaraminol infusion. Conclusion. A trial of metaraminol early in severe cases of calcium channel blocker and angiotensin II receptor antagonist toxicity may be of benefit, especially when conventional ionotropic treatment measures are failing. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) is a highly effective nonpharmacologic treatment for the management of depression and some other psychiatric disorders. Post-ECT agitation occurs in up to 12% of ECT treatments and is characterized by motor restlessness, irritability, disorientation, and panic-like behaviors. The severity of post-ECT agitation ranges from mild and self-limited to serious and severe forms requiring prompt medical intervention to protect the patient and the medical staff. In severe agitation medical management may be necessary which consists of using sedative agents, either benzodiazepines or propofol. The side-effects of these sedative agents, especially in the elderly population, necessitate finding ways that could help the prevention of the occurrence of agitation after ECT treatments. We report a 68-year-old female with major depression who was referred for ECT. She experienced severe post-ECT agitation requiring medical intervention after all ECT treatments. Administering of oral amlodipine (5 mg) one hour before ECT treatment successfully prevented the occurrence of post-ECT agitation in this patient. We briefly discuss the possible underlying mechanisms and pathophysiology of amlodipine in the prevention of post-ECT agitation. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction can predict cardiac outcomes in hypertension and reversing this abnormality has become an attractive therapeutic objective. We tested the hypothesis that blocking the angiotensin type 1 (AT1) receptor with valsartan in comparison with amlodipine would lead to an improvement in forearm resistance artery endothelial dysfunction. In total, 25 hypertensive subjects (mean age 60 years, SD 8) with a mean daytime ambulatory blood pressure (BP) of 154 (10)/97 (6) mmHg were randomized following a 3-week placebo run-in period to a double-blind, crossover trial of 16-week treatment periods with either valsartan or amlodipine, separated by a 3-week washout period. Intra-arterial infusions of acetylcholine (ACh) and NG-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide (NO) release, respectively. Coinfusion of ACh and L-NMMA was employed to investigate the existence of an NO-independent vasodilatory pathway. Valsartan and amlodipine each lowered the clinical BP to the same extent (139 [7]/87 [6] and 139 [11]/89 [4] mmHg, respectively). The vasodilatory response to ACh was significantly increased with valsartan (maximal percentage change in forearm blood flow (max. ΔFBF%) 301 [47] vs. 185 [34], mean [SEM]; P < 0.05) as compared with placebo, but remained unchanged with amlodipine. Both valsartan and amlodipine similarly increased the vasoconstrictive response to L-NMMA (max. ΔFBF%–43 [5], −42 [5], respectively, vs. –26 [3] baseline; P < 0.001). The vasodilatory response after coinfusion of ACh and L-NMMA was significantly ( P < 0.05) enhanced only with valsartan. Valsartan reserved peripheral endothelial dysfunction through both NO-dependent and -independent pathways, while for the same degree of BP control, amlodipine had only a partial effect on NO bioactivity. [ABSTRACT FROM AUTHOR]