amlodipine Norvasc
[Comparative effects of losartan and amlodipine on activities of sympathetic nerve, renin-angiotensin-aldosterone system and brain natriuretic peptide in the elderly hypertensive patients]

[Article in Japanese]

Tsutamoto T, Maeda K, Mabuchi N, Tsutsui T, Ohnishi M, Kinoshita M.

First Department of Internal Medicine, Shiga University of Medical Science.

This study investigated the comparative effects of losartan and amlodipine on the activation of the sympathetic nervous system, renin-angiotensin-aldosterone system (R-A-A system) and brain natriuretic peptide (BNP) in patients with essential hypertension. Twenty-four elderly patients who had received more than 12 months of antihypertensive treatment with amlodipine participated in this study. The treatment regimen of 5 mg/day amlodipine was changed to 50 mg/day losartan. Plasma catecholamines (norepinephrine, epinephrine and dopamine), active renin, aldosterone and BNP concentration were measured before and after an average of 5 months of losartan treatment. After losartan treatment, blood pressures were not changed, suggesting the comparable effect of 50 mg losartan and 5 mg amlodipine on elevated blood pressure. Losartan significantly reduced norepinephrine (799 +/- 277 pg/mL vs. 692 +/- 268 pg/mL, p < 0.05) and aldosterone concentration (81.2 +/- 35.3 pg/mL vs. 55.2 +/- 17.7 pg/mL, p < 0.01), whereas there were not any changes in BNP concentrations. These findings suggested that losartan might be superior to amlodipine in prevention of chronic or intermittent sympathetic hyperactivity and enhanced R-A-A system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12073593&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Beneficial effects of therapy on the progression of structural remodeling during healing after reperfused and nonreperfused myocardial infarction: different effects on different parameters.

Jugdutt BI, Menon V.

Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

BACKGROUND: Structural left ventricular remodeling after myocardial infarction is a complex process with several pathophysiologic descriptors that can be modified by pharmacotherapy. However, the possibility that different classes of antiremodeling agents might exert different effects on different remodeling parameters after reperfused and nonreperfused myocardial infarction has not been systematically studied. METHODS AND RESULTS: We measured detailed left ventricular remodeling parameters in vivo (echocardiograms) repeatedly over 6 weeks and ex vivo (planimetry) at 6 weeks after myocardial infarction in 36 dogs randomized (factorial design) after reperfused or nonreperfused myocardial infarction to 6 weeks of twice daily oral therapy with the calcium channel blocker amlodipine (5 mg), the angiotensin-converting enzyme inhibitor enalapril (5 mg) or placebo, and 18 matching sham or control animals. Compared to placebo and control groups over 6 weeks, both agents reduced left ventricular loading and limited overall remodeling in both reperfused and nonreperfused groups, but there were pertinent differences. Enalapril limited the increase in left ventricular asynergy in the reperfused group. Both enalapril and amlodipine limited infarct zone thinning in the nonreperfused groups but increased infarct zone thinning in the reperfused groups, despite preserved infarct zone collagen with amlodipine. Enalapril decreased left ventricular diastolic volume and mass more than amlodipine in the reperfused group and increased left ventricular ejection fraction in the nonreperfused group. Both agents limited regional and global shape deformation in reperfused and non-reperfused groups. Diastolic wall stress in the infarct zone decreased with amlodipine, and increased with enalapril and reperfusion. CONCLUSIONS: Different antiremodeling therapies may exert different effects on different remodeling parameters during healing after reperfused myocardial infarction. Significant interactions occur during reperfusion. More than one variable may be needed for the comprehensive assessment of the antiremodeling efficacy of different therapies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12075398&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
The economic efficiency of amlodipine in the treatment of coronary atherosclerosis--an analysis based on the PREVENT study.

Cathomas G, Erne P, Schwenkglenks M, Szucs TD.

Medical Department, Hirslanden Research, Zurich, Switzerland.

BACKGROUND: High health service expenditure on the one hand, and the politically declared objective of stability of statutory contributions and restriction of public funds on the other hand, have been central points of the political and social discussion for several years. The over-proportional increase in health service expenditure is obvious, compared to the increase in the costs of living. PATIENTS AND METHODS: Cost-effectiveness of amlodipine in the treatment of coronary atherosclerosis was analysed by applying the results of the PREVENT study to the Swiss health system. RESULTS: Calculation of effectiveness shows an additional life expectancy of 0.083 years in the amlodipine cohort compared to the placebo cohort, over an observation period of 3 years. The cost-effectiveness of amlodipine treatment is approximately CHF 14,650 per life-year gained. CONCLUSION: The administration of the calcium antagonist amlodipine in CHD patients is cost-effective.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12085980&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
The effects of calcium channel antagonists on coronary nitrite outflow in isolated rat heart.

Djuric D, Mitrovic V, Jakovljevic V.

Institute of Physiology, Belgrade University School of Medicine, Belgrade, F.R. Yugoslavia. drdjuric61 hotmail.com

The aim of the study was to compare the effects of Ca2+ channel antagonists on coronary endothelial L-arginine/NO system in isolated rat heart. The hearts of male Wistar albino rats (n = 36, age 8 weeks, body mass 180-200 g) were perfused according to Langendorff technique at gradually increased coronary perfusion pressure (CPP) which induced flow-dependent NO release (nitrite outflow). The experiments were performed during control condition or in the presence of different Ca2+ channel antagonists: nifedipine (CAS 21829-25-4, 30 nmol/l), diltiazem (CAS 42399-41-7, 3 mumol/l), verapamil (CAS 52-53-9, 0.4 mumol/l) or amlodipine (CAS 88150-42-9, 100 nmol/l) were administered separately. Also, nifedipine or amlodipine were administered in combination with an inhibitor of nitric oxide synthase (NOS), L-NAME (NG-nitro-L-arginine-methylester, 30 mumol/l). Coronary flow (CF) varied in autoregulatory range from 3.93 +/- 0.25 ml/min/g wt at 50 cmH2O to 4.49 +/- 0.31 ml/min/g wt at 90 cmH2O. In autoregulatory range nitrite outflow varied from 1.80 +/- 0.22 nmol/min/g wt at 50 cmH2O to 2.21 +/- 0.25 nmol/min/g wt at 90 cmH2O and was strictly parallel with the CPP-CF (coronary perfusion pressure/coronary flow) curve. The autoregulatory range of CF was significantly extended (40-100 cmH2O) under the influence of nifedipine. Hemodynamic effects were accompanied by significant changes in nitrite outflow in all groups except for the verapamil group. Nifedipine and diltiazem induced statistically significant increases of nitrite outflow in coronary venous effluent, strictly parallel with the CPP-CF curve, from 58% at 120 cmH2O to 190% at 40 cmH2O and from 74% at 120 cmH2O to 166% at 40 cmH2O, respectively. On the contrary, amlodipine induced significant reduction of nitrite outflow which was stronger at the lower value of CPP (44-46% at 40-80 cmH2O), compared to the higher value of CPP (32-37% at 100-120 cmH2O). When L-NAME was applied in combination with nifedipine or amlodipine, CF was significantly reduced with parallel changes in nitrite outflow. The results show that Ca2+ channel antagonists (verapamil, diltiazem, nifedipine and amlodipine) strongly influence the coronary endothelial L-arginine/NO system in isolated rat heart leading to the difference in nitrite outflow.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12087921&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Impaired regulation of renal oxygen consumption in spontaneously hypertensive rats.

Adler S, Huang H.

Department of Medicine, Division of Nephrology, New York Medical College, 19 Bradhurst Avenue, Suite 0100, Hawthorne, NY 10532, USA. stephen nymc.edu

Abnormalities of nitric oxide (NO) and oxygen radical synthesis and of oxygen consumption have been described in the spontaneously hypertensive rat (SHR) and may contribute to the pathogenesis of hypertension. NO plays a role in the regulation of renal oxygen consumption in normal kidney, so the response of renal cortical oxygen consumption to stimulators of NO production before and after the addition of the superoxide scavenging agent tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) was studied. Baseline cortical oxygen consumption was similar in SHR and Wistar-Kyoto (WKY) rats (SHR: 600 +/- 55 nmol O(2)/min per g, WKY: 611 +/- 51 nmol O(2)/min per g, P > 0.05). Addition of bradykinin, enalaprilat, and amlodipine decreased oxygen consumption significantly less in SHR than WKY (SHR: bradykinin -13.9 +/- 1.9%, enalaprilat -15.3 +/- 1.6%, amlodipine -11.9 +/- 0.7%; WKY: bradykinin -22.8 +/- 1.0%, enalaprilat -24.1 +/- 2.0%, amlodipine -20.7 +/- 2.3%; P < 0.05), consistent with less NO effect in SHR. Addition of tempol reversed the defects in responsiveness to enalaprilat and amlodipine, suggesting that inactivation of NO by superoxide contributes to decreased NO availability. The response to an NO donor was similar in both groups and was unaffected by the addition of tempol. These results demonstrate that NO availability in the kidney is decreased in SHR, resulting in increased oxygen consumption. This effect is due to enhanced production of superoxide in SHR. By lowering intrarenal oxygen levels, reduced NO may contribute to susceptibility to injury and renal fibrosis. Increasing NO production, decreasing oxidant stress, or both might prevent these changes by improving renal oxygenation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12089374&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
[Determination of amlodipine in human plasma by liquid chromatography-tandem mass spectrometry]

[Article in Chinese]

Chen XY, Luan Y, Zhong DF, Du ZM.

Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110015, China.

AIM: To develop a sensitive and specific LC/MS/MS method for determination of amlodipine in human plasma. METHODS: Amlodipine and internal standard 4'-hydroxypropafenone were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax C8 column. The mobile phase consisted of acetonitrile-water-formic acid (75:35:1), at a flow-rate of 0.4 mL.min-1. A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor-->product ion combinations of m/z 409-->238 and m/z 358-->116 was used to quantify amlodipine and internal standard, respectively. RESULTS: The linear calibration curves were obtained in the concentration range of 0.4-16.0 ng.mL-1. The limit of quantification was 0.4 ng.mL-1. Each plasma sample was chromatographed within 3.7 min. The method was successfully used in several pharmacokinetic studies for amlodipine. More than 1,500 plasma samples were assayed within two weeks. CONCLUSION: The method is proved to be suitable for clinical investigation of amlodipine pharmacokinetics, which offers advantages of specificity, speed, and greater sensitivity over the previously reported methods.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12579861&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
A retrospective electronic chart review of blood pressure changes in elderly patients treated with amlodipine or an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.

Dollar A, Brown C, Putnam D, McLaughlin T, Okamoto L, Arocho R.

Cardiology of Georgia, Atlanta, USA.

BACKGROUND: Despite the high costs of managing hypertension, pharmacologic intervention is cost-effective, particularly in patients at highest risk for cardiovascular events. The prevalence of hypertension in the elderly and the age-associated risks of coronary artery disease and stroke suggest that early identification and aggressive treatment should be priorities in this population. OBJECTIVE: The aim of this study was to compare the effect of amlodipine and angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in the treatment of essential hypertension in elderly patients (>60 years) in an actual practice setting. METHODS: This was a retrospective cohort analysis using electronic medical records stored in the Physicians Data Corporation cardiology database. Patients aged >60 years who received care from a cardiologist and who had a recorded diagnosis of hypertension during 1997 or 1998 were identified. For inclusion, patients had to have received an initial prescription for amlodipine, an ACE inhibitor, or an ARB at the index visit. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings from the index visit and > or =1 subsequent visit (<180 days after the index visit) were assessed. RESULTS: A total of 192 patients (56.3% male; mean age, 71.9 years) met the inclusion criteria. Amlodipine-treated patients experienced a mean decrease in SBP of 26.7 mm Hg, compared with 18.8 mm Hg in patients receiving an ARB and 15.8 mm Hg for patients receiving an ACE inhibitor (P = 0.008, amlodipine vs ACE inhibitor). DBP decreased 8.8 mm Hg with amlodipine, 8.7 mm Hg with an ARB, and 6.2 mm Hg with an ACE inhibitor. After adjusting for age, sex, and disease severity, amlodipine-treated patients were -4 times as likely to move to a better blood pressure stage than patients treated with an ARB or an ACE inhibitor (odds ratio, ARB vs amlodipine: 0.245; 95% CI, 0.080-0.753; odds ratio, ACE inhibitor vs amlodipine: 0.234; 95% CI, 0.072-0.761). CONCLUSION: Results of this study indicate that in patients aged >60 years, amlodipine may be an effective therapy for hypertension.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12117083&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Raman spectroscopic investigation of atorvastatin, amlodipine, and both on atherosclerotic plaque development in APOE*3 Leiden transgenic mice.

van de Poll SW, Delsing DJ, Jukema JW, Princen HM, Havekes LM, Puppels GJ, van der Laarse A.

Department of Cardiology, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.

Raman spectroscopy allows quantitative, non-destructive evaluation of entire, intact atherosclerotic plaques. We quantified the anti-atherosclerotic effects of atorvastatin and amlodipine on progression of atherosclerosis using post-mortem Raman spectroscopic plaque imaging in 28 APOE*3 Leiden transgenic mice who were fed a high fat/high cholesterol diet for 28 weeks. Mice were assigned to a control group receiving the diet alone or to groups that received the diet with either 0.01% w/w atorvastatin, 0.002% w/w amlodipine, or the combination. The entire excised aortic arch was scanned with Raman microspectroscopy for quantitation of the distribution of cholesterol and calcification content. When mice had been treated with atorvastatin, cholesterol accumulation and calcification in the aortic arch was reduced by 91 and 98%, respectively, (both P<0.001). Amlodipine did not reduce the cholesterol content but reduced calcification of the aorta by 69% (P<0.05). The combination of amlodipine and atorvastatin was as effective as atorvastatin alone. This study demonstrates the strong atheroprotective potential of atorvastatin. In addition it is demonstrated that amlodipine reduces mineralization of atherosclerotic plaque. No synergistic effect of the combination of amlodipine and atorvastatin on plaque development is demonstrated. This study encourages Raman spectroscopic evaluations of anti-atherosclerotic drugs in larger animals and humans in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12119194&dopt=Abstract amlodipine Norvasc