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Frontiers in Pharmacology 2021The present study aimed to investigate the effects of irbesartan and amlodipine besylate tablets on the intestinal microflora of rats with hypertensive renal damage....
The present study aimed to investigate the effects of irbesartan and amlodipine besylate tablets on the intestinal microflora of rats with hypertensive renal damage. Eighteen 12-week-old male spontaneous hypertensive rats were randomly divided into three groups. The Ai-HDG group was given irbesartan at 15 mg/kg per day by gavage, the Ci-HDG group was given amlodipine besylate tablets at 1 mg/kg per day by gavage, and the Wi-HDG group, i.e., the control, was given the same dose of distilled water per day by gavage. The treatment lasted for 6 weeks. Six 12-week-old male Wistar-Kyoto rats were used as the reference group. Bacterial DNA was extracted from the feces of all the rats for high-throughput sequencing before and after the experiment. Operational taxonomic units were used to analyze the species of the intestinal flora, and the alpha diversity index was used to analyze the diversity. The relative abundance of the intestinal microflora in each group of rats was therefore analyzed at the phylum and genus levels. Compared with the Wi-HDG group, the alpha diversity of the Ai-HDG group increased ( < 0.05), while in the Ci-HDG group, only the Shannon index increased significantly. At the phylum level, compared with the control group, in the Ai-HDG and Ci-HDG groups, Firmicutes (F) decreased, Bacteroides (B) increased, and the F/B ratio decreased ( < 0.05). At the genus level, compared with the Wi-HDG group, the Ai-HDG and Ci-HDG groups did not show a significantly delayed decline in lactic acid bacteria. However, in the Ai-HDG group, the relative abundance of increased. After the administration of irbesartan and amlodipine besylate, the disorder of intestinal flora in the rats with hypertensive renal damage improved. However, irbesartan was better than amlodipine besylate at improving the diversity of the intestinal flora in these rats.
PubMed: 35273491
DOI: 10.3389/fphar.2021.778072 -
Journal of Family Medicine and Primary... Jul 2022Angioedema is swelling that mostly involves the soft tissue of the eyelids, nose, throat, tongue, mouth, or genitals. Angiotensin converting enzyme inhibitors induced...
Angioedema is swelling that mostly involves the soft tissue of the eyelids, nose, throat, tongue, mouth, or genitals. Angiotensin converting enzyme inhibitors induced angioedema is a rare but potentially dangerous adverse effect. A 52-year-old female patient attended the emergency department with the history swelling over the eyes and face past 3 days and having difficulty in swallowing of the food. Her medical history revealed that the patient was recently diagnosed with hypertension and was on the combination of Telmisartan and Amlodipin (40 mg + 5 mg). The medicines were immediately stopped and the patient was managed symptomatically for angioedema. The symptoms declined after 5 days of discontinuity of medicines. The case report can be considered as rare adverse effects of the Telmisartan. Angiotensin receptor blockers induced angioedema is a rare presentation.
PubMed: 36387724
DOI: 10.4103/jfmpc.jfmpc_1710_21 -
Acta Cardiologica Sinica Nov 2022Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases. Although treating these factors...
Beneficial Effects of Fixed-Dose Combination of Amlodipine and Atorvastatin in Patients with Concomitant Hypertension and Hypercholesterolemia: A Multi-Institutional Cohort Study.
BACKGROUND
Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases. Although treating these factors simultaneously is recommended by current guidelines, only short-term clinical results are available.
OBJECTIVES
To examine the longer-term efficacy and safety of fixed-dose combination (FDC) versus free combination of amlodipine and atorvastatin in patients with concomitant hypertension and hypercholesterolemia.
METHODS
Patients with hypertension and hypercholesterolemia were stratified into three groups [FDC of amlodipine 5 mg/atorvastatin 10 mg (Fixed 5/10), FDC of amlodipine 5 mg/atorvastatin 20 mg (Fixed 5/20), and free combination of amlodipine 5 mg/atorvastatin 10 mg (Free 5/10)]. After inverse probability of treatment weighting, the composite CV outcome, liver function, BP, LDL-C and glycated hemoglobin (HbA1c) changes were compared.
RESULTS
A total of 1,788 patients were eligible for analysis, and the mean follow-up period was 1.7 year. There was no significant difference in the composite CV outcome among the three groups (Fixed 5/10 6.1%, Fixed 5/20 6.3% and Free 5/10 6.0%). The LDL-C level was significantly reduced in the Fixed 5/20 group (-35.7 mg/dL) compared to the Fixed 5/10 (-23.6 mg/dL) and Free 5/10 (-10.3 mg/dL) groups (p = 0.001 and < 0.001, respectively). The changes in HbA1c were similar among the three groups.
CONCLUSIONS
FDC of amlodipine and atorvastatin, especially the regimen with a higher dosage of statins, significantly reduced the mid-term LDL-C level compared to a free combination in patients with concomitant hypertension and hypercholesterolemia. Blood sugar level was not significantly changed by this aggressive treatment strategy.
PubMed: 36440238
DOI: 10.6515/ACS.202211_38(6).20220529A -
Toxics Sep 2022Fimasartan, amlodipine, and hydrochlorothiazide are commonly used in combination therapies as antihypertensive drugs. This study aimed to develop and validate an...
Simultaneous Analysis of a Combination of Anti-Hypertensive Drugs, Fimasartan, Amlodipine, and Hydrochlorothiazide, in Rats Using LC-MS/MS and Subsequent Application to Pharmacokinetic Drug Interaction with Red Ginseng Extract.
Fimasartan, amlodipine, and hydrochlorothiazide are commonly used in combination therapies as antihypertensive drugs. This study aimed to develop and validate an analytical method for fimasartan, its active and major metabolite fimasartan-amide, amlodipine, and hydrochlorothiazide in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The standard calibration curves for fimasartan (1−500 ng/mL), its active and major metabolite fimasartan-amide (0.3−100 ng/mL), amlodipine (0.5−200 ng/mL), and hydrochlorothiazide (5−5000 ng/mL) were linear with R2 > 0.9964, and the inter- and intra-day accuracy and precision and stability were within the acceptable criteria. Using this validated analytical method, the pharmacokinetic interaction of these triple combination drugs between single administration and concomitant administration of the triple combination was investigated; the results did not reveal a significant difference in any of the pharmacokinetic parameters. Based on these results, we investigated the effects of red ginseng extract (RGE) on the pharmacokinetics of fimasartan, fimasartan-amide, amlodipine, and hydrochlorothiazide after oral administration of the combination in rats. No significant difference was observed in the pharmacokinetic parameters of fimasartan, fimasartan-amide, amlodipine, and hydrochlorothiazide, except for the Tmax values of amlodipine. The delayed Tmax value of amlodipine was attributed to its decreased intestinal permeability after repeated RGE treatments. In conclusion, using a combination of antihypertensive drugs and simultaneous analytical methods, we established efficient drug interaction and toxicokinetic studies using a small number of animals.
PubMed: 36287856
DOI: 10.3390/toxics10100576 -
The Journal of Clinical Investigation Sep 2021Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for...
Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers.
Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Cerebral Small Vessel Diseases; Cerebrovascular Circulation; Dementia, Vascular; Disease Models, Animal; Drug Therapy, Combination; Eplerenone; Heart Disease Risk Factors; Humans; Hyperemia; Hypertension; Losartan; Male; Mice; Microvessels; Potassium Channels, Inwardly Rectifying; Renin-Angiotensin System
PubMed: 34351870
DOI: 10.1172/JCI149029 -
The Chinese Journal of Physiology 2023The purpose of this study was to elucidate the therapeutic effect of different antihypertensive drugs (amlodipine and perindopril) on hypertension induced by apatinib...
Comparison of antihypertensive drugs amlodipine and perindopril on blood pressure variability after long-term treatment of hypertension induced by apatinib and bevacizumab.
The purpose of this study was to elucidate the therapeutic effect of different antihypertensive drugs (amlodipine and perindopril) on hypertension induced by apatinib and bevacizumab. Sixty patients with hypertension treated with apatinib or bevacizumab were selected and divided into two groups: one group was treated with amlodipine and the other group was treated with perindopril. Before and after treatment, the dynamic blood pressure (BP) measurement (systolic BP [SBP] and diastolic BP [DBP]), echocardiography (left ventricular end-diastolic diameter, interventricular septal thickness [IVST], left ventricular posterior wall thickness [LVPWT], and left atrial diameter [LAD]), and detection of nitric oxide (NO) content in venous blood were performed. In the amlodipine group, the 24hSBP, 24hSSD, 24hSCV, daytime mean SBP (dSBP), daytime mean SSD (dSSD), daytime mean SBP CV, night mean SBP (nSBP), night mean SSD, 24hDBP, 24hDSD, 24 h DBP CV, daytime mean DBP (dDBP), daytime mean DSD (dDSD), daytime mean DBP CV, night mean DBP (nDBP), LAD, and LAD index (LADi) after treatment were all lower than before treatment, while NO was higher than before treatment (all P < 0.05). In the perindopril group, the 24hSBP, dSBP, nSBP, 24hDBP, dDBP, nDBP, LAD, LADi, IVST, LVPWT, and left ventricular mass index (LVMI) after treatment were lower than before treatment, and NO level after treatment was higher than before treatment (all P < 0.05). After treatment, the 24hSBP, 24hSSD, dSBP, dSSD, nSBP, 24hDBP, 24hDSD, dDBP, dDSD, nDBP, night mean DSD, and NO were all lower while the LAD, LADi, IVST, LVPWT, and LVMI were higher in the amlodipine group than those in the perindopril group (all P < 0.05). Our study suggests that the SBP and DBP variability of amlodipine in the treatment of hypertension induced by apatinib and bevacizumab is slightly better than that of perindopril, but the effect of perindopril in improving endothelial function indices NO and echocardiographic data is better than that of amlodipine.
Topics: Humans; Antihypertensive Agents; Perindopril; Amlodipine; Blood Pressure; Bevacizumab; Hypertension; Treatment Outcome
PubMed: 37322624
DOI: 10.4103/cjop.CJOP-D-22-00158 -
Gut Microbes 2024S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of...
S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further experiments revealed that the observed liver inflammation and dysfunction were not attributable to direct effects of S-amlodipine on the liver. Metagenome sequencing analysis revealed that S-amlodipine treatment led to alterations in the gut microbiome of rats, with the bloom of (4.5 ~ 6.6-fold increase) and a decrease in (1,613.4 ~ 2,000-fold decrease) and (20.6202.7-fold decrease), subsequently causing an increase in the gut bacterial lipopolysaccharide (LPS) content (1.4 ~ 1.5-fold increase in feces). S-amlodipine treatment also induced damage to the intestinal barrier and increased intestinal permeability, as confirmed by elevated levels of fecal albumin; furthermore, the flux of gut bacterial LPS into the bloodstream through the portal vein resulted in an increase in serum LPS content (3.3 ~ 4-fold increase). LPS induces liver inflammation and subsequent dysfunction in rats by activating the TLR4 pathway. This study is the first to show that S-amlodipine induces liver inflammation and dysfunction by perturbing the rat gut microbiome. These results indicate the adverse effects of S-amlodipine on the liver and provide a rich understanding of the safety of long-term S-amlodipine administration.
Topics: Rats; Male; Animals; Amlodipine; Gastrointestinal Microbiome; Lipopolysaccharides; Escherichia coli; Liver; Bacteria; Inflammation
PubMed: 38400721
DOI: 10.1080/19490976.2024.2316923 -
Turkish Journal of Pharmaceutical... Jun 2021The aim of this study was to develop and optimize a simple, cost-effective, and robust high-performance liquid chromatography (HPLC) method by taking an experimental...
OBJECTIVES
The aim of this study was to develop and optimize a simple, cost-effective, and robust high-performance liquid chromatography (HPLC) method by taking an experimental design approach to the assay and dissolution analysis of amlodipine besylate and enalapril maleate from a fixed-dose combination tablet.
MATERIALS AND METHODS
The chromatographic analysis was performed on a C18 column (4.6x250 mm id., particle size of 5 μm). The injection volume was 5 μL, and the detection wavelength was 215 nm. A Box-Behnken design was used to test the robustness of the method. The flow rate (1, 1.2, and 1.4 mL/min), column temperature (25°C, 30°C, and 35°C), methanol ratio of the mobile phase (5, 10, and 15%), and pH of the mobile phase (2.8, 3, and 3.2) were selected as independent variables. The method was validated according to International Conference on Harmonization guidelines. Dissolution of the tablets was performed by using USP apparatus 2 and analyzed using the optimized HPLC method. Multivariate linear regression analysis and ANOVA were used in the statistical evaluation.
RESULTS
Linear models were fitted for all variables. The flow rate was the most significant factor affecting the APIs' concentrations. The optimized method included the following parameters: Column temperature of 25°C, 10% methanol as the mobile phase, pH of 2.95, and flow rate of 1.205 mL/min. Retention times were 3.8 min and 7.9 min for enalapril and amlodipine, respectively. The method was found to be linear in the range of 0.8-24 μg/mL (R >0.999) and 1.6-48 μg/mL (R >0.999) for amlodipine and enalapril, respectively. Both APIs were dissolved more than 85% within 10 min.
CONCLUSION
The experimental design was proved as a useful tool for the determination and separation of enalapril maleate and amlodipine besylate in dosage forms. The optimized method can be used for performance and quality control tests of fixed-dose tablet combinations containing enalapril maleate and amlodipine besylate.
PubMed: 34157820
DOI: 10.4274/tjps.galenos.2020.89725 -
Diabetology & Metabolic Syndrome Mar 2023Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) [Ang-(1-7)] might have beneficial effects on the cardiovascular system. We...
BACKGROUND
Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) [Ang-(1-7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1-7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension.
METHODS
This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1-7) from baseline to week 24.
RESULTS
Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1-7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1-7) levels (r = - 0.252 and r = - 0.299, respectively). The change in Ang-(1-7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1-7) levels were an independent predictor of a reduction in albuminuria.
CONCLUSIONS
These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1-7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05189015.
PubMed: 36899369
DOI: 10.1186/s13098-023-00987-1 -
European Stroke Journal Mar 2023Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially...
The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial.
BACKGROUND
Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs.
AIMS
To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs.
DESIGN
TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose.
OUTCOMES
The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv).
DISCUSSION
TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs.
FUNDING
European Union's Horizon 2020 programme.
TRIAL REGISTRATION
NCT03082014.
Topics: Humans; Amlodipine; Antihypertensive Agents; Blood Pressure; Atenolol; Losartan; Cross-Over Studies; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 37021189
DOI: 10.1177/23969873221143570