Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An interim analysis of patient compliance is reported in 234 hypertension outpatients who were entered into a large-scale, open, crossover, comparative study between a new-generation calcium antagonist, amlodipine (5 mg, once daily), and nifedipine SR (20 mg, twice daily). An analysis was also performed on 84 outpatients with stable angina pectoris, who were included in an open, parallel study and received the same dosing regimen of either amlodipine or nifedipine SR as the patients in the hypertension arm of the study. In the hypertensive patients, there were significant differences in favor of amlodipine, using all four methods to assess patient compliance. In the angina patients, a significant difference between the groups in favor of amlodipine was only found using the "correct dosing" and the "timing compliance" methods. With the traditional pill-counting and also the "taking compliance" methods, there was no observed difference in compliance between the two groups. It was concluded that, in terms of patient compliance, once-daily amlodipine was markedly superior to twice-daily nifedipine in the crossover study involving the hypertension patients. Amlodipine was also better tolerated than nifedipine. In the angina arm of the study, patient compliance was again better with amlodipine than with nifedipine, but there was no difference observed in the levels of tolerance between the two therapies.
 ...
PMID:Patient compliance and therapeutic coverage: amlodipine versus nifedipine SR in the treatment of hypertension and angina: interim results. Steering Committee and Cardiologists and General Practitioners involved in the Belgium Multicentre Study on Patient Compliance. 915 55

Twenty two patients having mild to moderate hypertension were treated with a single daily dose of amlodipine for 4 weeks. Satisfactory response defined as final diastolic blood pressure < 90 mm of Hg and a reduction from baseline values > 10 mm of Hg could be achieved in 81.8% of patients in supine position and 70% of patients in standing position. Thirteen patients responded to 5 mg dose and 9 patients required 10 mg. Postural hypotension and reflex tachycardia were absent. Three patients has mild leg cramps and constipation. No deleterious effects were observed on liver, kidney and hemopoetic function, or on E.C.G. Changes. Amlodipine given once daily is effective and safe, and is a useful addition to the existing armamentarium of antihypertensive drugs.
 ...
PMID:Evaluation of amlodipine in mild to moderate hypertension--a clinical report. 928 37

The purpose of the study was to compare the antianginal and hypotensive efficacy and tolerability of 8 weeks of treatment with amlodipine taken once daily and nifedipine taken twice daily in patients with stable exertional angina pectoris and mild-to-moderate hypertension. Following a 2-week placebo run-in-period 13 patients were randomized to receive amlodipine (5 to 10 mg once daily) and 8 patients to receive nifedipine (20 or 40 mg twice daily) in an 8-week treatment phase. Antianginal efficacy was assessed with angina diares, investigators, and patients global evaluations and with treadmill exercise test during placebo run-in-period and after 8 weeks of the therapy. Amlodipine significantly reduced both weekly anginal attacks and consumption of glyceryl trinitrate tablets. This effect was more pronounced compared to efficacy of nifedipine. Exercise tolerance was also improved more markedly after amlodipine than after nifedipine treatment. Amlodipine treatment resulted in significant increase in total exercise time, increase the exercise time to angina onset, increase time to ST segment depression, decrease in ST segment depression, decrease in total duration of ST segment depression and decrease in duration of pain. In patients treated with nifedipine only favourable effect was significant decrease in total duration of ST segment depression, without significant changes of other examined parameters. Both drugs decreased blood pressure with no significant change in heart rate. No serious adverse events occurred in any patients during therapy with amlodipine as well as with nifedipine. The results of the study demonstrate that amlodipine has markedly better anti-anginal efficacy than nifedipine with respect to the most of the parameters examined. However both drugs showed comparable antihypertensive action and both were well tolerated by angina patients. The good anti-anginal and hypotensive efficacy and safety of amiodipine with once daily dosage regimen makes this drug an excellent choice of treatment for hypertensive patients with severe coronary artery disease.
 ...
PMID:[Comparative study to assess the efficacy and adverse effects of amlodipine and nifedipine retard in patients with stable exertional angina and hypertension]. 938 Aug 7

Migration of monocytes into the subendothelial space of the aorta has been considered to be an important event in the development of atherosclerosis. Because hypertension is commonly associated with atherosclerosis, we studied the effect of applied pressure on the migration of monocytes. Direct applied pressure increased the migration (P < .001) of monocytes across a filter when compared with normal atmospheric pressure. The migration of monocytes was found to be directly related to the amount of the applied pressure. Amlodipine, a calcium channel blocker, attenuated the migration of monocytes under normal as well as increased pressure conditions in a dose-dependent manner. These studies provide a basis to speculate on the role of direct pressure in the migration of monocytes into the subendothelial space and the possibility that vasoactive agents may modulate the migration of monocytes independent of their pressure-lowering effect.
 ...
PMID:Pressure modulates monocyte migration. 939 50

The purpose of the present study was to examine the effects of a long-acting calcium antagonist, amlodipine, on the development of cardiac remodeling. Dihydropyridine calcium antagonists have been used widely for many years in the treatment of hypertension and angina pectoris. It has been reported, however, that a prototype of dihydropyridines, nifedipine, does not reduce mortality of patients with ischemic heart disease, possibly because of reflex stimulation of the sympathetic nervous system. A calcium antagonist, amlodipine, has been reported to have potential benefits by virtue of a gradual onset of action and a long duration of effects. Amlodipine (8 mg/kg per day, once a day) or nifedipine (24 mg/kg per day, three times a day) was administered to spontaneously hypertensive 12-week-old rats for 12 weeks. Left ventricular wall thickness was measured by echocardiography, and relative amounts of myosin heavy chain isoforms were assessed by pyrophosphate gels. Expressions of "fetal type" genes and type 1 collagen gene were examined by Northern blot analysis. Amlodipine and nifedipine both markedly reduced systolic blood pressure. However, the decrease in systolic blood pressure caused by nifedipine continued for no more than 8 hours, whereas the blood pressure-lowering effect of amlodipine continued for more than 16 hours post dose. Amlodipine markedly reduced left ventricular wall thickness, whereas nifedipine only weakly attenuated an increase in the wall thickness. Amlodipine, but not nifedipine, prevented an increase in the relative amount of V3 myosin heavy chain isoform and suppressed an increase in mRNA levels of beta-myosin heavy chain, skeletal alpha-actin, and type 1 collagen. Unlike nifedipine, amlodipine effectively prevented cardiac remodeling secondary to high blood pressure at biochemical levels and morphological levels. These results suggest that a long-acting calcium antagonist is more effective than a short-acting one in preventing organ injury in hypertensive subjects.
Hypertension 1998 Jan
PMID:Efficient inhibition of the development of cardiac remodeling by a long-acting calcium antagonist amlodipine. 944 87

The calcium antagonist amlodipine may have the potential for expanded use in children owing to its physiochemistry and pharmacokinetic profile that facilitates once-daily dosing in a liquid formulation. Its safety and efficacy have not been previously evaluated in children. A retrospective analysis of 15 pediatric bone marrow transplant patients who had amlodipine incorporated into their antihypertensive drug regimen reveals significantly lower blood pressure as compared with baseline therapy (123.5+/-2.1 mmHg and 117.2+/-2.2 mmHg, systolic blood pressure before and during amlodipine, P<0.05; 81.5+/-1.8 mmHg and 75.5+/-2.6 mmHg, diastolic blood pressure before and during amlodipine, P<0.05). Amlodipine provided improved blood pressure control in this cohort and may provide a valuable pharmacologic alternative for treatment of pediatric hypertension.
 ...
PMID:Efficacy of amlodipine in pediatric bone marrow transplant patients. 947 97

Vascular smooth muscle cells (VSMC) are involved in the pathogenesis of hypertension and coronary artery disease. Amlodipine, a calcium channel blocker of the dihydropyridine type, is widely used in the therapy of these diseases, and has been shown to reduce the progression of the underlying pathophysiological mechanisms, such as atherosclerosis and restenosis. Research on the impact of calcium channel blockers on cell behavior has revealed an antiproliferative effect on VSMC. Cell proliferation is tightly controlled by permanent interaction of cells with their surrounding microenvironment, the extracellular matrix (ECM). The ECM is subjected to a continuous turnover and implicated in (i) stabilization and compartmentalization of tissue architecture and (ii) local binding and preservation of growth factors and cytokines. These growth factors and cytokines can be released during degradation of the ECM, and can function as local inflammatory factors without de novo synthesis. In this context, we assessed the effects of amlodipine on the composition of the ECM and related factors. We investigated the effects of amlodipine on (i) the regulation of cellular cholesterol metabolism, (ii) the activation of genes encoding for inflammatory factors, (iii) gene expression and turnover of ECM compounds, and (iv) the activity of matrix-degrading enzymes. Most of these effects of calcium channel blockers require direct induction of gene expression. In this respect, we demonstrate that amlodipine increases expression of the cytokine interleukin-6 by directly activating the respective gene promoter in human VSMC.
 ...
PMID:Effects of amlodipine on gene expression and extracellular matrix formation in human vascular smooth muscle cells and fibroblasts: implications for vascular protection. 948 93

In both atherosclerosis and arterial hypertension, structural and functional abnormalities result in vascular hypertrophy that is associated with an increased ratio of vascular media thickness to lumen diameter and hyperreactivity of vascular smooth muscle cells (VSMCs), resulting in uncontrolled cell migration and growth in vivo. In culture, VSMCs isolated from the spontaneously hypertensive rat (SHR) also display exaggerated growth and/or proliferation compared to VSMCs isolated from normotensive control Wistar Kyoto (WKY) rats. In vitro studies of cultured VSMCs can therefore be used as a model to investigate the mechanisms whereby a drug such as amlodipine can exert its antihypertensive and antiatherogenic effects. The present in vitro investigations examine the mechanisms whereby amlodipine reduces VSMC growth/proliferation promoted by basic fibroblast growth factor (bFGF), a peptide growth factor likely to participate in the vascular smooth muscle hypertrophy of the SHR. VSMCs from SHR and/or WKY rat aortae were isolated, passaged, and cultured. The influence of amlodipine on VSMC growth/proliferation was studied by measuring DNA synthesis and cell number under experimental conditions, which allowed us to determine the cell cycle phase in which amlodipine exerts its effects. Amlodipine was found to inhibit growth and bFGF-induced DNA synthesis in a concentration-dependent manner. Delayed addition of amlodipine showed that the drug exerts its effect early in the G1 phase, a result that was confirmed by the finding that amlodipine could not inhibit bFGF-induced DNA synthesis in VSMCs arrested at the G1/S boundary. In comparative experiments, the inhibitory effect of amlodipine on both cell growth and DNA synthesis was found to be of similar magnitude in SHR- and WKY-derived VSMCs. It is therefore likely that by modulating cell growth/proliferation induced by bFGF, amlodipine may reduce the vascular hypertrophy of the SHR. Since amlodipine also has been found to inhibit VSMC migration, one may reasonably envisage that these characteristics are important components of the antiatherogenic properties of the drug.
 ...
PMID:Amlodipine and vascular hypertrophy. 948 98

Platelets are known to contribute to the initiation and progression of coronary artery narrowing by atherosclerotic plaques. Platelets also initiate periodic occlusive coronary arterial thrombosis that leads to unstable angina and myocardial infarction. Aspirin is the most widely used platelet inhibitor. However, if blood levels of epinephrine are elevated, some of the platelet inhibition produced by aspirin is diminished. Amlodipine, a second generation dihydropyridine calcium channel blocker, was studied in a widely used dog model of experimental coronary artery thrombosis. Amlodipine 1 mg/kg alone or amlodipine 0.4 mg/kg with 5 mg/kg of aspirin I.V. completely abolished the experimental coronary thrombosis and prevented the exacerbation of coronary thrombosis by epinephrine 0.2 microg/kg/min. This protective effect did not appear until 60 minutes after the amlodipine was given, suggesting a delayed onset of action. Long-acting dihydropyridine calcium channel blockers are used in patients with hypertension, angina, and coronary artery disease. They also may offer the patient some protection against fatal or nonfatal myocardial infarction via their platelet-inhibiting effects.
 ...
PMID:Inhibition of platelet activity in vivo by amlodipine alone and combined with aspirin. 948 2

In patients with congestive heart failure (CHF) receiving therapy with angiotensin-converting enzyme (ACE) inhibition, institution of calcium channel antagonism with amlodipine provided favorable effects. The goal of the present study was to define potential mechanisms for these effects by measuring left ventricular function, hemodynamics, and neurohormonal system activity in a model of CHF in which amlodipine treatment had been instituted either as a monotherapy or in combination with ACE inhibition. Thirty-two pigs were instrumented to allow measurement of cardiac index, total systemic resistance index, and neurohormonal activity in the conscious state and assigned to one of four groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n = 8), (2) amlodipine (1.5 mg x kg(-1) x d[-1]) and pacing (n = 8), (3) ACE inhibition (fosinopril 1.0 mg/kg BID) and pacing (n = 8), and (4) amlodipine and ACE inhibition (1.0 mg x kg(-1) x d(-1) and 1.0 mg/kg BID, respectively) and pacing (n = 8). Measurements were obtained in the normal control state and after the completion of the treatment protocols. With rapid pacing, basal resting cardiac index was reduced compared with control values (2.7+/-0.2 versus 4.7+/-0.1 L x min(-1) x m(-2), respectively, P<.05) and increased from rapid pacing-only values with either amlodipine or combination therapy (3.7+/-0.3 and 4.4+/-0.5 L x min(-1) x m(-2), respectively, P<.05). Basal resting total systemic resistance index was higher in the rapid pacing-only group compared with control values (2731+/-263 versus 1721+/-53 dyne x s x cm(-5) x m2, respectively, P<.05), was reduced with either amlodipine treatment or ACE inhibition (2125+/-226 and 2379+/-222 dyne x s x cm(-5) x m2, respectively, P<.05), and was normalized with combination therapy. Plasma catecholamines, renin activity, and endothelin levels were increased threefold with rapid pacing. Amlodipine, either as a monotherapy or in combination with ACE inhibition, did not result in increased plasma catecholamines and renin activity compared with the rapid pacing-only group. Furthermore, combination therapy reduced steady state norepinephrine and normalized epinephrine levels. The results of the present study demonstrated that monotherapy with either amlodipine or ACE inhibition provides beneficial effects in this pacing model of CHF. Combined amlodipine and ACE inhibition provided greater benefit with respect to vascular resistance properties and neurohormonal system activity compared with either monotherapy.
Hypertension 1998 Mar
PMID:Amlodipine monotherapy, angiotensin-converting enzyme inhibition, and combination therapy with pacing-induced heart failure. 949 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>