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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 -
Journal of Clinical Hypertension... Nov 2021Various single-pill combinations (SPCs) have been introduced to improve drug compliance and clinical efficacy. However, there is a lack of real-world evidence regarding...
Clinical effectiveness and safety of amlodipine/losartan-based single-pill combination therapy in patients with hypertension: Findings from real-world, multicenter observational databases.
Various single-pill combinations (SPCs) have been introduced to improve drug compliance and clinical efficacy. However, there is a lack of real-world evidence regarding the effectiveness of these SPCs for hypertension. This study evaluated the real-world clinical efficacy and safety of amlodipine/losartan-based SPC therapies in patients with hypertension in a real-world setting. A total of 15 538 patients treated with amlodipine/losartan-based SPCs [amlodipine + losartan (AL), amlodipine + losartan + rosuvastatin (ALR), and amlodipine + losartan + chlorthalidone (ALC)] were selected from the database of three tertiary hospitals in Korea. The efficacy endpoints were target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) achievement rates. Safety was evaluated based on laboratory parameters. Drug adherence was defined as the proportion of medication days covered (PDC). The target BP attainment rate was above 90% and was similar among the three groups. Although many patients in the AL and ALC groups took statins, the target LDL-C attainment rate was significantly higher in the ALR group than in the AL and ALC groups. Safety endpoints were not significantly different among the groups, except serum uric acid level and incidence rate of new-onset hyperuricemia, which were significantly lower in the AL and ALR groups than in the ALC group. The PDC was > 90% in all groups. In the real-world hypertensive patients, amlodipine/losartan-based SPC therapy demonstrated good target BP achievement rates. Especially, rosuvastatin-combination SPC showed better target LDL-C goal achievement rate compared to the other SPCs. All three amlodipine/losartan-based SPC had excellent drug adherence.
Topics: Amlodipine; Antihypertensive Agents; Humans; Hypertension; Losartan; Treatment Outcome; Uric Acid
PubMed: 34714968
DOI: 10.1111/jch.14380 -
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 -
American Journal of Cardiovascular... Oct 2013This article discusses racial/ethnic disparities in hypertension, with particular focus on non-white populations including blacks, Hispanics/Latinos, and Asians.... (Review)
Review
This article discusses racial/ethnic disparities in hypertension, with particular focus on non-white populations including blacks, Hispanics/Latinos, and Asians. Hypertension and its related morbidity and mortality affect a disproportionate number of black patients compared with white patients. Blacks, Hispanics/Latinos, and Asians have poor rates of hypertension awareness, treatment, and control. Given the high prevalence of comorbidities (e.g., obesity, diabetes, and metabolic syndrome) in these populations, renin-angiotensin-aldosterone system blockers are a good choice for foundation therapy. This review also discusses the importance of adherence and persistence with antihypertensive medication, which remain suboptimal in these non-white populations. Evidence suggests improvement with the use of single-pill combination therapy. Lastly, clinical trial data on the antihypertensive efficacy and safety of the combination of a dihydropyridine calcium channel blocker and an angiotensin receptor blocker, a widely utilized combination, in non-white populations are presented. PubMed was searched using the title/abstract key words (amlodipine AND valsartan AND [hypertension OR hypertensive] AND [black(s) OR African American(s) OR Hispanic(s) OR Latino(s) OR Mexican(s) OR Asian(s)]). In total, eight studies in patients with stage 1 or 2 hypertension were identified (n = 1,111 black, n = 389 Hispanic/Latino, and n = 3,094 Asian). Results showed that treatment with the combination of amlodipine plus valsartan is a reasonable choice for initial therapy or in patients who fail to respond to monotherapy. These drug classes have complementary mechanisms of action and, when used concomitantly, the magnitude of blood pressure lowering in these non-white populations is generally comparable with that seen in non-Hispanic white patients.
Topics: Black or African American; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Asian People; Drug Combinations; Health Status Disparities; Hispanic or Latino; Humans; Hypertension; Medication Adherence; Tetrazoles; Treatment Outcome
PubMed: 23784267
DOI: 10.1007/s40256-013-0033-4 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2006Drug-induced gingival hyperplasia is a serious concern both for the patient and the clinician. A 45 year-old Caucasian male patient with hypertension, who received... (Review)
Review
Drug-induced gingival hyperplasia is a serious concern both for the patient and the clinician. A 45 year-old Caucasian male patient with hypertension, who received amlodipine (10 mg/day, single dose orally) for two months, sought medical attention because of the new-onset gingival enlargement. On clinical examination a generalized and firm overgrowth of the gingival throughout the maxilla and the mandible were evident. The lack of gingival inflammation and purulent discharge were other features of the clinical scenario. Histological assessment of the biopsy specimen revealed the hyperplasia of connective tissue, epithelial acanthosis, and elongated rete ridges along with few inflammatory cells. The histological and the clinical evidences were consistent with amlodipine-induced gingival hyperplasia. We believe that the present report indicates the most rapidly developed case of amlodipine-induced gingival hyperplasia reported to date. The related literature is reviewed and the underlying pathogenic mechanisms of this rare side-effect are discussed here.
Topics: Amlodipine; Antihypertensive Agents; Gingival Hyperplasia; Humans; Male; Middle Aged
PubMed: 17072250
DOI: No ID Found -
Analytical Sciences : the International... Jul 2021The simple reflective absorbance spectrophotometric smartphone device for point-of-monitoring amlodipine is presented here for the first time. The immediate analysis of...
A Portable Reflective Absorbance Spectrophotometric Smartphone Device for the Rapid and Highly Accurate Determination of Amlodipine in Pharmaceutical Formulation and Human Urine Samples.
The simple reflective absorbance spectrophotometric smartphone device for point-of-monitoring amlodipine is presented here for the first time. The immediate analysis of amlodipine in the human urine of the patients who suffered severe side effects of this drug is very important for the diagnosis, treatment, and reduction of the death rate. This measurement technique is based on the charge-transfer complex between amlodipine and picric acid, which forms a yellow product. This product can absorb light intensity from an LED strip and measure through the Blue channel from the RGB mode with a smartphone application. The linear relationship for amlodipine monitoring was found in a wide range from 100.0 μg L to 140.0 mg L (R = 0.999), and the limit of detection was found to be 25.0 μg L. Our proposed method can be applied to different smartphone brands with consistent sensitivity of amlodipine detection. Additionally, the determination of amlodipine in pharmaceutical formulations and human urine samples was demonstrated by our proposed method. The recoveries were indicated in the range of 98.60 - 100.00%, which is at the acceptable level for pharmacy. This method offers an interweaving of basic technology and chemical analysis with being environmentally friendly due to reducing the complex instrument and the amount of organic waste compared to the chromatographic technique and efficient use for the detection of amlodipine. Hence, this method can be applied for prompt medical diagnoses and laboratories with limited budget resources.
Topics: Amlodipine; Drug Compounding; Humans; Smartphone; Spectrophotometry
PubMed: 33229823
DOI: 10.2116/analsci.20P349 -
Clinical and Experimental Hypertension... Dec 2023To investigate the actions of amlodipine-folic acid (amlodipine-FA) preparation on hypertension and cardiovascular in renal hypertensive rats with hyperhomocysteinemia...
OBJECTIVES
To investigate the actions of amlodipine-folic acid (amlodipine-FA) preparation on hypertension and cardiovascular in renal hypertensive rats with hyperhomocysteinemia (HHcy), so as to provide experimental basis for clinical research of amlodipine folic acid tablets.
METHODS
Rats model of renal hypertension with HHcy were established. The rats were randomly divided into groups of model, amlodipine, folic acid (FA) and amlodipine-FA of various dosages. Normal rats were used as normal control group. Blood pressure, Hcy as well as plasma NO, ET-1 and hemodynamics were assayed. Histological alterations of heart and abdominal aorta were also examined.
RESULTS
Compared with the normal group, blood pressure, plasma Hcy, and NO of the rats in model group were significantly increased, while the plasma ET-1 was decreased. Compared with the normal group, the animals in the model group had reduced cardiac function, thickened wall of the aorta and narrowed lumen. In FA group and amlodipine group, the rat plasma NO was increased while ET-1 was decreased, the protective effect of amlodipine-FA group on endothelial cells was further enhanced. In amlodipine group, the rat hemodynamics (LVSP, LVEDP and ±dp/dt, et al.) and vascular damage were significantly reduced, while in amlodipine-FA group, the heart function were further improved, and myocardial and vascular hypertrophy were significantly reduced.
CONCLUSIONS
As compared to amlodipine alone, amlodipine -FA can lower both blood pressure and plasma Hcy, significantly enhancing vascular endothelial function to protect the heart and blood vessel in renal hypertensive rats with HHcy.
Topics: Rats; Animals; Folic Acid; Amlodipine; Endothelial Cells; Hypertension; Kidney; Homocysteine; Hyperhomocysteinemia
PubMed: 37154141
DOI: 10.1080/10641963.2023.2205058 -
Medicine Mar 2016To evaluate the effects of a fixed combination of olmesartan/amlodipine compared with olmesartan or amlodipine alone on some parameters of endothelial damage in... (Randomized Controlled Trial)
Randomized Controlled Trial
To evaluate the effects of a fixed combination of olmesartan/amlodipine compared with olmesartan or amlodipine alone on some parameters of endothelial damage in diabetic, hypertensive patients.We enrolled 221 patients; 74 were randomized to olmesartan 20 mg, 72 to amlodipine 10 mg, and 75 to olmesartan/amlodipine fixed combination 20/5 mg for 12 months. We assessed blood pressure monthly; in addition, we also assessed at baseline, and after 6 and 12 months, the following parameters: lipoprotein (a), myeloperoxidase (MPO), isoprostanes, and paraoxonase-1 (PON-1). Blood pressure values obtained with fixed olmesartan/amlodipine combination were significantly lower than those reached with single monotherapies. There was a reduction of lipoprotein (a), and isoprostanes levels with olmesartan/amlodipine fixed combination, both compared with baseline, and with single monotherapies. On the other hand, there was an increase of PON-1 with fixed olmesartan/amlodipine combination, both compared with baseline, and with single drugs. All treatments reduced MPO compared with baseline; however, in group-to-group comparison, MPO reduction was greater with olmesartan/amlodipine fixed combination. Fixed combination of olmesartan/amlodipine was more effective than single monotherapies in reducing oxidative stress, especially in increasing PON-1, and reducing isoprostanes levels in diabetic and hypertensive patients.
Topics: Adult; Amlodipine; Antihypertensive Agents; Aryldialkylphosphatase; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Imidazoles; Isoprostanes; Male; Oxidative Stress; Peroxidase; Tetrazoles
PubMed: 27043671
DOI: 10.1097/MD.0000000000003084 -
High Blood Pressure & Cardiovascular... Mar 2023Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require... (Review)
Review
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.
Topics: Humans; Aged; Antihypertensive Agents; Blood Pressure; Olmesartan Medoxomil; Drug Therapy, Combination; Hypertension; Amlodipine; Hydrochlorothiazide; Leukemia, Myeloid, Acute
PubMed: 36696054
DOI: 10.1007/s40292-023-00563-8 -
Journal of the American Heart... Aug 2019Background Amlodipine is used for the treatment of hypertension, but reports on its use in early pregnancy are limited. Methods and Results In the present study, we...
Background Amlodipine is used for the treatment of hypertension, but reports on its use in early pregnancy are limited. Methods and Results In the present study, we recruited 231 women with chronic hypertension, including those who received amlodipine or other antihypertensives during early pregnancy, and investigated frequencies of morphologic abnormalities in their 231 offspring. Specifically, we evaluated 48 neonates exposed to amlodipine in the first trimester (amlodipine group, Group A), 54 neonates exposed to antihypertensives other than amlodipine (other antihypertensive group, Group O), and 129 neonates not exposed to antihypertensives (no-antihypertensive group, Group N). The number of morphologic abnormalities of offspring in each group were 2 in Group A (4.2%; 95% CI, 0.51-14.25); 3 in Group O (5.6%; 95% CI, 1.16-15.39) and 6 in Group N (4.7%; 95% CI, 1.73-9.85). The odds ratio of the primary outcome comparing Group A and Group O was 0.74 (95% CI: 0.118-4.621) and Group A and Group N was 0.89 (95% CI: 0.174-4.575). Conclusions The odds of birth defects in Group A in the first trimester were not significantly different from those with or without other antihypertensives.
Topics: Abnormalities, Drug-Induced; Aged; Amlodipine; Antihypertensive Agents; Chronic Disease; Female; Follow-Up Studies; Humans; Hypertension; Infant, Newborn; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Prospective Studies
PubMed: 31345083
DOI: 10.1161/JAHA.119.012093