To assess whether ACE inhibitors are superior to alternative agents for the prevention of cardiovascular events in patients with hypertension and type 2 diabetes.
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Altogether 435 patients during preintervention and 445 during postintervention were studied. The incidence of potential DDIs was 53% (preintervention) and 41% (postintervention) [chi-square =11.27, p=0.001]. The average number of drugs per patient was 8.53 (pre-intervention) and 7.32 (post-intervention) [t=3.493, p=0.001]. Sixty-four percent of the potential DDIs were of 'Moderate' type and 58% had a 'Delayed' onset in both the phases. Seventy percent of the potential DDIs during the pre-intervention phase and 61% during post-intervention phase had a 'Good' documentation status. Pharmacokinetic mechanism accounted for 45% of the potential DDIs during preintervention and 36% in the post-intervention phase. Cardiovascular drugs accounted for 36% of the potential DDIs during pre-intervention and 33.2% during post-intervention phase. Furosemide was the high risk drug responsible for DDIs in both phases. The most common potential DDIs observed were between amlodipine and atenolol (4.82%) (preintervention) and frusemide and aspirin (5.20%) (postintervention).
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Treatment with C. pareira extract ameliorates thyroxin-induced oxidative stress and cardiac hypertrophy, probably through amelioration of calcineurin activity and augmentation of antioxidant enzyme activities.
In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging.
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The goals of this article were to review the currently available antihypertensive agents used in the treatment of pediatric hypertension and to assist clinicians in selecting the most appropriate treatment.
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We pretreated human umbilical venous endothelial cells with increasing doses of amlodipine (10(-8)-10(-6) M) followed by the addition of Ang II. Cell apoptosis was assessed by acridine orange/ethidium bromide staining and by annexin-V/propidium iodide double-labeled cytometry. The involvement of the apoptosis regulators, Bcl-2, Bax, and lectin-like oxidized low-density lipoprotein receptor-1, was determined.
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A cross sectional survey was carried out in Kathmandu valley. Five different brands from each eight molecules of drugs (Paracetamol tablet, Cloxacillin capsule, Amlodipine tablet, Metformin tablet, Losartan tablet, Cefixime tablet, Ofloxacin tablet, Carbamazepine tablet) were purposively selected. Registration compliance was verified from Department of Drug Administration (DDA) and laboratorial analysis was done in two different laboratories.
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This study aimed to assess the relevance of specific potassium channels, such as inwardly or outwardly rectifying and calcium-regulated potassium channels, to the control of renin secretion. For this purpose we examined the effects of the K+ channel blockers 4-aminopyridine (1 mmol/l), barium (100 micromol/l), tetraethylammonium (2 mmol/l) and apamin (200 nmol/l) on basal renin secretion, on renin secretion stimulated by isoproterenol (10 nmol/l) and on the inhibition of renin secretion by angiotensin II (100-300 pmol/l) in the isolated rat kidney perfused at constant pressure. Whilst all four K+ channel blockers increased renal vascular resistance, only 4-aminopyridine and barium attenuated isoproterenol-stimulated renin secretion in an additive fashion and augmented the inhibitory effect of angiotensin II. These effects of K+ channel blockers were not changed by the L-type calcium channel blocker amlodipine (5 pmol/l), indicating that their effects on renin secretion are not due to voltage-operated calcium influx. Our data, moreover, suggest that potassium efflux from renal juxtaglomerular cells is not important for the inhibitory action of angiotensin II on renin secretion. As a consequence it appears that the membrane potential of renal juxtaglomerular cells per se is relevant to renin secretion such that membrane depolarization inhibits the exocytosis of renin whilst hyperpolarization favors renin secretion. By their activity, potassium channels can contribute to membrane hyperpolarization and thus facilitate renin secretion.
When drug-induced coronary spasm provocation tests are performed, a washout period of >48h for calcium channel blockers (CCBs) is uniformly recommended. However, each CCB has a distinct half-life, and little is known about the influence of prior oral administration of CCBs on acetylcholine provocation test to evaluate coronary vasomotor reaction.
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In view of the use of these often costly drugs for long-term therapy, monitoring of their use and its correlation with clinical outcomes and quality of life is essential to ensure the optimal use of health care resources.
This was an international, multicenter, randomized, double-blind, active-controlled, parallel-group study. Patients were randomized to receive once-daily treatment with amlodipine 5 to 10 mg + valsartan 160 mg or lisinopril 10 to 20 mg + HCTZ 12.5 rig for 6 weeks. Safety assessments included monitoring of all adverse events, vital signs, and hematology and biochemistry variables. Efficacy variables included the changes from baseline in MSDBP and mean sitting systolic BP (MSSBP), the response rate (MSDBP <90 mm Hg, or a >or= 10-mm Hg reduction from baseline), and the rate of DBP control (<90 mm Hg). The overall rate of BP control (proportion of patients with MSSBP/MSDBP <140/90 mm Hg) was evaluated in a post hoc analysis. Efficacy variables were summarized at each visit and at the end of the study (week 6, applying last-observation-carried-forward methodology) using descriptive statistics for the intent-to-treat population (all randomized patients with a baseline BP measurement and at least 1 post baseline BP measurement). Subgroup analyses of BP changes were performed in prespecified age groups (<65 and >or=65 years) and post hoc in patients with a baseline systolic BP <180 and >or=180 mm Hg.
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A cross-over study, comparing the effects of doxazosin, moduretic and amlodipine on plasma lipid and lipoprotein levels in 9 hypertensive Nigerians aged 35 to 65 years is presented. Doxazosin therapy had favourable lipid changes characterized by a statistically significant reduction in total cholesterol (TC) at 6 months. Though consistent reduction was observed in total triglycerides (TG) low density lipoprotein cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDLC) upto 6 months, no effect was seen on high density lipoprotein cholesterol (HDLC). This is against unfavourable increments in the mean values of TC, VLDLC, LDLC/HDLC and decrease in HDLC/TC during moduretic treatment phase. Amlodipine therapy did not alter the lipid and lipoprotein levels. The non-significant variation in the mean high density lipoprotein-cholesterol (HDLC) level observed with these agents, seem to suggest that HDL-cholesterol metabolism may be maintained during antihypertensive pharmacotherapy.
Spontaneous hemopericardium is a complication of anticoagulant therapy with not only vitamin-K-antagonists, but also with nonvitamin-K-antagonist oral anticoagulants. We report a polymorbid 75-year old male under a therapy with dabigatran, valsartan, amlodipine, nicorandil, furosemide, atorvastatin, bisoprolol, metformin, tizanidine, pantoprazole, and tramadol. He suffered from chest pain for 4 months. Coronary angiography showed only ectatic coronary arteries. He started taking nonsteroidal anti-inflammatory drugs. He was hospitalized because of dyspnea starting 10 days before admission, melena, and renal failure. Hemopericardium was diagnosed and pericardiocentesis yielded 2000 ml hemorrhagic fluid. Review of previous echocardiograms showed a 4 mm echo-free space, epicardial fat or pericardial effusion. A small (<10 mm) echo-free space in a patient on anticoagulant therapy should not be considered as trivial, but additional imaging studies should be carried out. If a pericardial effusion is newly diagnosed in a patient during anticoagulant therapy, the pharmacotherapy should be revised concerning potentially interacting drugs, like nonsteroidal anti-inflammatory drugs, and dosage of the anticoagulant drug. Vitamin-K-antagonists with their possibility of laboratory monitoring and availability of an antidote should be preferred over nonvitamin-K-antagonist oral anticoagulants.
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Thirteen cases of feline primary hyperaldosteronism were diagnosed based on clinical signs, serum biochemistry, plasma aldosterone concentration, adrenal imaging and histopathology of adrenal tissue. Two cases presented with blindness caused by systemic hypertension, whilst the remaining 11 cases showed weakness resulting from hypokalaemic polymyopathy. Elevated concentrations of plasma aldosterone and adrenocortical neoplasia were documented in all cases. Seven cases had adrenal adenomas (unilateral in five and bilateral in two) and six had unilateral adrenal carcinomas. Three cases underwent medical treatment only with amlodipine, spironolactone and potassium gluconate; two cases survived for 304 and 984 days until they were euthanased because of chronic renal failure, whilst the third case was euthanased at 50 days following failure of the owner to medicate the cat. Ten cases underwent surgical adrenalectomy following a successful stabilisation period on medical management. Five cases remain alive at the time of writing with follow-up periods of between 240 and 1803 days. Three cases were euthanased during or immediately following surgery because of surgical-induced haemorrhage. One cat was euthanased 14 days after surgery because of generalised sepsis, whilst the remaining cat was euthanased 1045 days after surgery because of anorexia and the development of a cranial abdominal mass. It is recommended that primary hyperaldosteronism should be considered as a differential diagnosis in middle-aged and older cats with hypokalaemic polymyopathy and/or systemic hypertension and should no longer be considered a rare condition.
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(-)-Gossypol; Alemtuzumab, Amlodipine, Anakinra, Azacitidine; Bazedoxifene acetate, Belinostat, Bevacizumab, BI-201335, BI-2536, Biphasic insulin aspart, Bortezomib; Cetuximab, CNTO-328, Custirsen sodium; Dacetuzumab; Elacytarabine, Erlotinib hydrochloride, Everolimus, Exenatide; Forodesine hydrochloride, Fostamatinib disodium, Frovatriptan; Ibutamoren mesilate, Imatinib mesylate, IMC-18F1, INCB-18424, Indacaterol, Insulin detemir, Insulin glargine, Insulin glulisine; KW-0761, KW-2449; Lapatinib ditosylate, Liraglutide; MK-2461, Mycophenolic acid sodium salt; Peginterferon alfa-2a, Pemetrexed disodium, Pioglitazone hydrochloride/metformin hydrochloride, Pregabalin; rBCG-30; Satraplatin, SB-743921, Short ragweed pollen allergenic extract, SNS-314, Sorafenib, Sugammadex sodium, Sunitinib malate; Teriparatide; Valsartan/amlodipine besylate, Vinflunine, Vorinostat.
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Although no significant differences were observed in the fasting plasma glucose level between the groups, the fasting plasma insulin level for group T was significantly lower than that for group C. Histopathologic examination showed that the ratio of small adipocytes in groups V and T was significantly higher than that in group C, with the ratio of large adipocytes and the mean adipocyte size shown to be significantly lower in groups V and T than in group C. Furthermore, group T was shown to have a significantly higher ratio of small adipocytes, a significantly lower ratio of large adipocytes, as well as a significantly lower mean adipocyte size, compared to group V.
Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses.
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Combination therapy is often required in patients with hypertension, and fixed-dose single-pill combinations have been shown to provide an easier regimen for patients, improving adherence. Irbesartan/amlodipine (Aprovasc®) is an angiotensin-receptor blocker/calcium-channel blocker fixed-dose single-pill combination, whose constituent drugs exert additive effects when coadministered. In two randomized, open-label, multicentre, phase III trials, fixed-dose combination therapy with irbesartan/amlodipine was more effective than continuation of irbesartan or amlodipine monotherapy in patients with hypertension not adequately controlled with initial irbesartan or amlodipine monotherapy; there was a significantly greater decrease from baseline in mean seated home systolic blood pressure (primary endpoint) with the fixed-dose combination. The fixed-dose combination was also associated with a greater decrease in mean seated home diastolic blood pressure and mean seated office systolic and diastolic blood pressure than monotherapy. The fixed-dose combination of irbesartan/amlodipine was well tolerated in these patients; most treatment-emergent adverse events were of mild or moderate severity. The most frequent adverse event was peripheral oedema, generally associated with amlodipine treatment.
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Bone is a dynamic organ system that is directly related to calcium and phosphor metabolism. Imbalance in these two parameters upon aging or menopause leads to osteoporosis. Recently, it was also shown by researchers that high blood pressure in elderly women is statistically associated with decreased bone mineral content at the femoral neck, which may increase the susceptibility to fractures. The aim of our study was to investigate the effects of different doses of amlodipine and lacidipine on ovariectomized rat femurs' calcium and phosphor content. Bone calcium and phosphor concentration was measured by a Wavelength Dispersive Spectrometer. Calcium contents of the rat femurs were significantly lower in the ovariectomized group than in the sham group eight weeks after the operation. Amlodipine treatment at doses of 1 and 3 mg/kg significantly increased the calcium (P<0.01) and phosphor concentrations (P<0.01) in the femurs of ovariectomized rats, compared to those of control (ovariectomized) group. Both doses of lacidipine (1 and 3 mg/kg) also effectively increased calcium concentrations (P<0.01) significantly in ovariectomized rats. On the other hand amlodipine treatment at doses of 1 and 3 mg/kg significantly increased the calcium (P<0.01) and phosphor concentrations (P<0.01) in the femurs of ovariectomized rats compared with those of the sham group. In conclusion, amlodipine and lacidipine improved the bone loss in an ovariectomy induced osteopenic rat model. Our findings suggest that potent calcium channel blockers such as amlodipine and lacidipine have a beneficial effect on bone metabolism, and an antihypertensive effect.
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Ginkgo leaf tablet (GLT) is an effective traditional Chinese multi-herbal formula, which is often combined with amlodipine for treating senile hypertension in clinic. The aim of this study was to study the pharmacokinetics of amlodipine after oral administration of amlodipine and GLT and to investigate the potential for pharmacokinetic herb-drug interactions between GLT and amlodipine in rats.
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Most of antihypertensive drugs used in adults do not have clinical trials to evaluate its effects in the pediatric population. Furthermore, the lack of familiarity with the pharmacokinetic characteristics of the child, raises problems to adjust the dose to the changing reality of a child. In this situation, clinical experience supports the use of some of these drugs in children with optimal results. With the addition to the pediatric field of calcium antagonists and ACE-inhibitors or ARB-II, they allow as to have greater potential therapeutic alternatives.
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Despite the well-known occurrence of antihypertensive drug-induced angioedema causing airway obstruction in adults, only 4 case reports have been previously published in children. At our institution, we describe 3 children who developed acute angioedema with upper airway obstruction after the chronic use of antihypertensive medications [2 drugs in the ACE inhibitor class (enalapril and lisinopril), and 1 drug in the calcium channel blocker class (CCB; amlodipine)]. In all 3 cases, the symptoms resolved within 1 week after the antihypertensive agent was discontinued.
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The compounds were incorporated in human umbilical vein endothelial cells (HUVECs) using native low-density lipoprotein as a carrier. The drug concentrations in HUVECs were measured by mass spectrometry. Human recombinant tumour necrosis factor-alpha was then incubated with HUVECs for 7 h at 37 degrees C for adhesion molecule expression.
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This prospective, randomized, open-label study enrolled 106 patients aged >/=18 years with mild-to-moderate hypertension. Patients were randomized to 5 mg of amlodipine or 20 mg of benazepril for 2 weeks; then, depending on randomization assignment, they were force-titrated to 10 mg of amlodipine or 40 mg of benazepril monotherapy, or to combination amlodipine (5 mg) and benazepril (20 mg) treatment for 22 weeks. Arterial distensibility was assessed using the DynaPulse ambulatory system, and left ventricular mass was assessed by echocardiography.
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Small AAA growth rates were lower than anticipated, but there was no significant impact of perindopril compared with placebo or placebo and amlodipine, combined despite more effective BP lowering.
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Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP).
A mechanistic investigation on the photodegradation of amlodipine, the corresponding besylate and a simple analogue lacking the beta-aminoethoxy group has been carried out in water and in organic solvents. Irradiation leads to aromatization to the corresponding pyridines through an oxygen-independent process. The quantum yield for amlodipine base is Phi congruent with 0.001 under UV-A light, about one order of magnitude larger than that for the model bearing no amino group, supporting intramolecular assistance by that group. The value of Phi increases up to ca. 0.01 at shorter wavelength. The photolability of this drug according to ICH criteria is justified by the high absorptivity in the UV-A range (epsilon(UV-A)), despite the low quantum yield. Some comments are added about the fact that product Phi x epsilon(UV-A) is more significative than Phi alone for the photolability (in solution) and about the lacking possibility to quench the photoreactivity where, as in the present case, this involves only short-lived intermediates.
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AII-induced vascular endothelial apoptosis and eNOS uncoupling were mediated by ASK1 and contributed to vascular injury in diastolic heart failure of salt-sensitive hypertension.