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

Amlodipine, a dihydropyrimidine calcium antagonist, is effective in the treatment of patients with mild to moderate hypertension at doses of 5-10 mg daily. The aim of the study reported here was to determine whether an early increase in dosage of amlodipine provided an advantage in terms of antihypertensive effect. This was a single-blind, randomised study in 115 patients with mild to moderate hypertension (diastolic blood pressure 95-114 mmHg) conducted at 10 centres with two parallel groups. Group I received amlodipine 5 mg once daily for the entire 10-week treatment period, while group II received amlodipine 5 mg once daily for two weeks, with the option to increase the dose to 10 mg once daily were the diastolic blood pressure to exceed 90 mmHg. The dose was increased in 40% of group II patients (20/50). Diastolic and systolic blood pressure decreased steadily until the end of the sixth week of treatment in both groups, with no statistically significant difference between the groups. The response rate (diastolic blood pressure < or = 90 mmHg) at the end of treatment was 84% in both groups. Because there is no advantage in an early increase in dosage of amlodipine in terms of antihypertensive effect, a dose increase should not be considered until after six weeks of treatment at 5 mg once daily.
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PMID:Is initial dose titration of amlodipine worthwhile in patients with mild to moderate hypertension? 1021 10

Amlodipine is a calcium antagonist with a long elimination half-life (35 to 50 h) allowing a once daily dosing in the treatment of hypertension. This randomized, double-blind study was performed to assess the residual antihypertensive effect of amlodipine 5 mg O.D. 3 days after discontinuing therapy in previously well-controlled mild to moderate hypertensive patients. Blood pressure (BP) was evaluated by conventional (OBP) and by ambulatory blood pressure monitoring (ABPM). Amlodipine 5 mg OD administered during a 6-week period, significantly reduced both OBP and ABPM mean values (p < 0.05), whereas no change in heart rate was observed. At the end of the active treatment period, adequately controlled patients were randomized either to amlodipine 5 mg OD (group A) or amlodipine for 12 days followed by a 3-day period on placebo. After this double-blind treatment phase, group P exhibited no significant increase in BP (assessed by OBP or ABPM) when compared to group A. In conclusion, the duration of action of amlodipine extends largely beyond the 24-h span, and when patients omit their treatment for 3 days BP does not significantly increase.
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PMID:Prolonged antihypertensive effect of amlodipine: a prospective double-blind randomized study. 1041 82

We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07+/-0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%-50% every 5-7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29+/-0.11 mg/kg per day for those < 13 years, 0.16+/-0.11 mg/kg per day for those > or = 13 years, 0.23+/-0.14 mg/kg per day for essential, hypertension and 0.24+/-0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.
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PMID:Efficacy of amlodipine in pediatric patients with hypertension. 1045 79

Amlodipine as a monotherapy was evaluated in 20 patients with mild, moderate, and severe hypertension over a 10 week period. After a washout period of 4 weeks, Amlodipine was administered at a dose of 5 mg once daily for 2 weeks and increased to 10 mg once daily if diastolic blood pressure did not fall to below 90 mmHg. At the end of the trial, diastolic blood pressure was reduced to below 90 mmHg in all but four patients. However, these four patients had greater than 20 mmHg reduction in diastolic blood pressure. There was a slight, but insignificant increase in heart rate. Dizziness and weakness occurred in one patient, otherwise, the drug was well tolerated. Laboratory tests, including plasma lipids done at the start and end of the trial, remained unchanged.
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PMID:Amlodipine as monotherapy in hypertensive Africans: clinical efficacy and safety studies. 1045 92

Mibefradil and amlodipine are calcium antagonists with different channel selectivities. Mibefradil blocks both L- and T-type calcium channels; although in the usual pharmacological doses, it predominantly blocks the T-type channels. In contrast, amlodipine selectively blocks L-type channels. The goal of the present study was to assess whether this differential selectivity would result in different effects on end-organ damage in experimental hypertension. For this purpose, deoxycorticosterone acetate (DOCA)-salt hypertensive rats were treated either with equipotent doses of mibefradil or amlodipine (30 mg. kg(-1). d(-1) as food admix). Despite the fact that both drugs decreased systolic arterial pressure to the same extent (140+/-5 mm Hg in the mibefradil group and 144+/-3 mm Hg in the amlodipine group versus 225+/-5 mm Hg in the untreated-DOCA group), only mibefradil decreased proteinuria (35. 5+/-6.5 versus 103.3+/-14.1 mg/24 h in untreated DOCA-salt animals) and prevented glomerular lesions. Both drugs, however, prevented the occurrence of vascular renal lesions. To elucidate the mechanism responsible for this difference, we evaluated in an additional series of experiments the effects of mibefradil and amlodipine on plasma and renal renin concentrations, as well as the effects of the addition of enalapril, an ACE inhibitor, given on top of both drugs on proteinuria. Amlodipine, in contrast to mibefradil, markedly stimulated the plasma (17.8+/-2.6 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 3.9+/-0.4 ng Ang I. mL(-1). h(-1) in the mibefradil group and 3.2+/-0.3 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) and renal (2.42+/-0.37 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 0.36+/-0.04 ng Ang I. mL(-1). h(-1) in the mibefradil group and 0.26+/-0.08 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) renin concentrations. Stimulation of the renin-angiotensin system could explain the absence of a renal protective effect of amlodipine. This was also suggested by the fact that enalapril given in addition to amlodipine could decrease proteinuria. In conclusion, T-type channel blockade by mibefradil decreases blood pressure without stimulation of the renin-angiotensin system and therefore prevents most of the glomerular damage in DOCA hypertensive rats.
Hypertension 1999 Oct
PMID:Contrasting effects of selective T- and L-type calcium channel blockade on glomerular damage in DOCA hypertensive rats. 1052 45

Transgenic rats (TGRs) TGR(mREN2)27 are characterized by fulminant hypertension, an inverse circadian blood pressure rhythm, and severe hypertensive target organ damage. In the present study, we evaluated cardiovascular risk factors, renal function, and urinary protein loss in transgenic rats before and after treatment with the calcium channel blocker amlodipine. Amlodipine was injected intraperitoneally in a dose of 5 mg/kg/day, either once daily at 8.00 h or twice daily in divided doses at 8.00 and 20.00 h. Untreated TGRs and Sprague-Dawley rats served as hypertensive and normotensive controls, respectively. Before and after 5 weeks of treatment, rats were placed in metabolic cages for sampling of urine. Prior to treatment, urinary excretion rates of protein, albumin, and Ca2+ were significantly higher in TGRs than in Sprague-Dawley controls. Urinary excretion of protein and albumin was reduced by 5 weeks of amlodipine treatment, whereas the excretion of Ca2+ was not affected. The reductions in renal proteinuria and albuminuria by amlodipine treatment were significantly correlated with the treatment-induced decrease in blood pressure. These findings indicate that blood pressure itself is an important contributor to albumin loss by the kidney in renin-dependent hypertension of TGRs.
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PMID:Cardiovascular risk, renal hypertensive damage, and effects of amlodipine treatment in transgenic TGR(mREN2)27 rats. 1055 84

Calcium channel blockers (CCBs) blunt postural skin vasoconstriction, an autoregulatory mechanism that minimizes gravitational increases in capillary pressure and avoids fluid extravasation when standing. To evaluate the dose-response relation between this pharmacological interference and dependent edema, a frequent side effect of CCBs during antihypertensive treatment, skin blood flow (laser Doppler flowmetry) at the dorsum of the foot, both supine and with the limb passively placed 50 cm below the heart level, and leg weight (Archimedes principle) were measured at baseline, during increasing doses of the dihydropyridine amlodipine (5 and 10 mg UID each for 2 weeks), and after drug withdrawal in 10 hypertensive men. Because angiotensin-converting enzyme inhibitors may attenuate ankle swelling by CCBs, those parameters were evaluated according to a similar design during amlodipine (10 mg UID) and enalapril (20 mg UID) combined (n=10). As a control, the effect of enalapril monotherapy (10 and 20 mg UID for 2 weeks each) was evaluated in a third series of patients (n=8). Amlodipine (5 mg UID) increased leg weight without modifying postural vasoconstriction (the percent skin blood flow decrease from horizontal to dependent position), which indicates that extravascular fluid shift was independent of postural skin vasoconstriction. At 10 mg UID, however, amlodipine blunted postural vasoconstriction and increased leg weight further, which suggests that skin blood flow autoregulation limited additional fluid transfer. Both parameters normalized after drug withdrawal. Enalapril per se did not affect cutaneous vasomotion or leg weight but reduced the amount of dependent fluid extravasation by the CCB despite a persistent antagonism for postural vasoconstrictor responses.
Hypertension 2000 Feb
PMID:Amlodipine, enalapril, and dependent leg edema in essential hypertension. 1067 7

Hypertension is often referred to as the "silent killer" because most hypertensive patients are asymptomatic until cardiovascular sequelae such as stroke, myocardial infarction, heart failure, or renal failure occur. LVH is a common finding in patients with hypertension, especially African-Americans. Data from the Framingham Heart Study indicate that LVH is an independent risk factor for major cardiovascular events. In the Amlodipine Cardiovascular Community Trial, 37% of 124 hypertensive patients screened by means of echocardiography had LVH at baseline. Although there was no difference in the prevalence of LVH by gender or age, African-American patients were nearly twice as likely to have LVH than white patients (64% vs. 34%, p<0.05). Hence, aggressive therapy to reach target goals outlined in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) is especially important in this group of patients. Even lifestyle modifications such as weight reduction and limitation of salt intake, if sufficiently aggressive, can lead to regression of LVH, as demonstrated by results of the Treatment of Mild Hypertension Study (TOMHS). Most classes of antihypertensive drugs are effective in causing regression of LVH. Vasodilators, such as minoxidil and hydralazine, do not have an effect on regression, possibly because reflex tachycardia and stimulation of catecholamines and the renin-angiotensin system associated with these agents may negate the benefit of reduced afterload. There is some controversy regarding the ability of the angiotensin receptor blockers to reduce LVH. In some studies, these agents were associated with regression, whereas in others they were not. Whether targeting LVH as the primary treatment goal in hypertensive patients will have long-term benefits on outcome above and beyond simply reducing blood pressure is not clear.
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PMID:Case 3: A patient with systemic hypertension and left ventricular hypertrophy. 1072 68

The objective of this investigation was to compare changes in antioxidant status (together with other metabolites relevant to hypertension) in plasma and cardiac tissue from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY), following 8 weeks of treatment with lisinopril (angiotensin converting enzyme inhibitor) or amlodipine (Ca(2+) channel antagonist) respectively. There was no significant difference in the levels of total antioxidant capacity, retinol, urea, albumin or triglyceride in plasma from SHR or WKY rats, with or without lisinopril or amlodipine treatment. However in SHR rats, levels of alpha-tocopherol were substantially reduced in both plasma (-54% WKY, P<0.01) and cardiac tissue (-43% WKY, P<0.05). Treatment with lisinopril ameliorated reduced levels of plasma alpha-tocopherol in SHR rats, but not in cardiac tissue. Amlodipine treatment had no effect on alpha-tocopherol levels in plasma or cardiac tissue in SHR rats. In SHR rats total cholesterol levels were significantly lower thanWKY controls (-36%, P<0.001). This effect was reversed in lisinopril treated SHR rats (+27%, P<0.01). Plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were reduced in untreated SHR rats (P<0.025) when compared to WKY controls; neither lisinopril nor amlodipine treatment significantly altered these parameters. These findings suggest possible alternative mechanisms of action for lisinopril, and reinforce its use in hypertensive patients or patients with left ventricular hypertrophy.
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PMID:Effects of lisinopril and amlodipine on antioxidant status in experimental hypertension. 1090 Feb 88

The safety and efficacy of Amlodipine (AML) for mild to moderate hypertension was evaluated in a "real life" setting. This open non-comparative trial included 123 men and 143 women (age 30-91 years, mean 59.4). All had sitting diastolic blood pressure (DBP) between 95 and 115 mmHg, confirmed in most by 2 baseline measurements, 2 weeks apart. Eligible patients were given AML 5 mg daily as add-on or monotherapy and were evaluated 4 weeks later. If DBP was then > 90 mmHg, the daily dose was raised to 10 mg; those with < 90 mmHg remained on 5 mg. AML was continued for 8 weeks. Other BP-lowering drugs were unchanged. Of the original 266 patients 22 (8.2%) withdrew due to adverse events (AE), and others were protocol violators, lost to follow-up or withdrew, leaving 211 available for efficacy analysis. In this major group BP was reduced from 165 +/- 15/101 +/- 4 to 139 +/- 11/83 +/- 5 after 12 weeks of AML (p < 0.05). The reduction was greater in those under 70 years, from 173 +/- 12/100 +/- 5 to 142 +/- 12/80 +/- 4 (p < 0.05). In those with BMI > 30 kg/m2, BP decreased from 165 +/- 15/101 +/- 5 to 140 +/- 12/83 +/- 5 (p < 0.05). Mean change in heart rate was -1.5 bpm (p < 0.05). Mean final AML dose was 5.5 mg/day. The most common AML-related AE requiring cessation of the drug was pedal edema in 2.6% of the 266 patients; in 3.7% it persisted during therapy. Other AE occurring in > 1% were dizziness in 1.8%, headache 1.5%, flushing 1.1% and fatigue 1.1%. We conclude that AML is an effective and well-tolerated antihypertensive suitable for most hypertensive patients.
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PMID:[Multicenter community-based trial of amlodipine in hypertension in Israel]. 1095 90


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