Antihypertensive effect of amlodipine compared with nifedipine retard in patients with mild and moderate essential hypertension

OBJECTIVE: The present study was undertaken to evaluate the efficacy and safety of amlodipine for hypertension treatment in comparison with nifedipine retard. METHODS: We examined 31 patients with arterial blood pressure approximately 155-165 mmHg/100-105 mm Hg at the beginning of the trial. It was a randomized double-blind, parallel-group trial including two groups of patients. Patients of the first group were given active amlodipine and nifedipine retard placebo during 6 weeks, while the second group was given active nifedipine retard and amlodipine placebo. Statistical analysis was made using the paired Student's t-test, chi-square test and ANOVA test. RESULTS: At end point we observed significant decrease in arterial blood pressure after treatment of both drugs. The treatment with nifedipine retard increased the mean heart rate of patients. Amlodipine therapy in comparison to nifedipine retard did not change the heart rate in treated patients. Safety parameters: SGOT, SGTP, creatinine and others were in laboratory norms ranges. CONCLUSION: Amlodipine proved to be an effective, more safe and better-tolerated therapeutical alternative for hypertension management than nifedipine retard.     

Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients

OBJECTIVE: To compare the acute and chronic effects of nifedipine retard (NPA), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg). DESIGN AND METHODS: After 3-4 weeks' placebo treatment, patients of both sexes were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 weeks. Initially, for the first 2 weeks, the lowest dose of each drug was used, but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg. Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood samples were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges. RESULTS: Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightly only with amlodipine (P < 0.05). Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acute and chronic treatments with NPA (n = 19) increased norepinephrine levels (P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5-6 h after chronic treatments. Although administration of amlodipine (n = 22) did not increase norepinephrine levels transiently either after acute or after chronic administration, it did induce a sustained rise in basal norepinephrine levels by more than 50% after chronic therapy (P < 0.01). Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05). CONCLUSIONS: The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs. The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations.     

Parallel comparative trial of amlodipine and nitrendipine monotherapy in patients with essential hypertension

OBJECTIVES: To compare the blood pressure effects of two dihydropyridine calcium channel blockers, amlodipine and nitrendipine, in 488 patients with essential hypertension. METHODS: The study used a randomized, single-blind design of 4 weeks' duration conducted at four medical centres in China. Patients were randomized to receive either amlodipine monotherapy (5-10 mg once daily; n = 334) or nitrendipine (10 mg twice or three times daily; n = 1 54). Blood pressure was evaluated by standard blood pressure measurements before and after treatment, and by 24 h ambulatory blood pressure monitoring in a subgroup of patients (n = 18). RESULTS: Both systolic and diastolic blood pressures were reduced from baseline after 4 weeks of amlodipine and nitrendipine monotherapy. Diastolic blood pressure was reduced by 14.4% in the amlodipine group, which was significantly better than the 13.0% reduction in the nitrendipine group (P< 0.05). In addition, blood pressure response rates were significantly better with amlodipine monotherapy than with nitrendipine monotherapy. In the subgroup of patients undergoing 24 h ambulatory blood pressure monitoring, both systolic and diastolic blood pressure were reduced from baseline in the amlodipine and nitrendipine groups. Adverse effects were generally mild, with dizziness, flushing, palpitation, headache, drowsiness and ankle oedema being the most common. Rushing and headache were more frequent in the nitrendipine group than in the amlodipine group (P< 0.05 for flushing and P<0.01 for headache). CONCLUSIONS: Amlodipine monotherapy reduced blood pressure more effectively than nitrendipine monotherapy in patients with essential hypertension and was associated with fewer adverse events.     

Intracellular calcium and blood pressure: comparison between primary hyperparathyroidism and essential hypertension

Intracellular calcium has been reported to be increased in essential hypertension, and thought to play a role in its genesis through facilitation of vascular smooth muscle contraction. Since hypertension is more prevalent in primary hyperparathyroidism, intracellular calcium may also be increased in this condition. To investigate whether the hyperparathyroid condition, i.e., hypercalcemia and increased PTH per se, could be associated with high intracellular calcium, we measured intracellular calcium in platelets with the Quin-2 AM fluorometric method in 11 normotensive patients with primary hyperparathyroidism, 15 patients with essential hypertension, and 18 normal controls, all matched for age and sex. We repeated the measurements in 9 of the hyperparathyroid patients after successful surgery. We found that intracellular calcium was higher in normotensive patients with primary hyperparathyroidism than in normal controls (198 +/- 24 vs 113 +/- 11 nM, p < 0.05), but lower than in patients with essential hypertension (198 +/- 24 vs 286 +/- 38 nM, p < 0.05). Successful removal of a parathyroid adenoma decreased intracellular calcium from 215 +/- 22 to 116 +/- 19 nM, (p < 0.01). In the patients with primary hyperparathyroidism, intracellular calcium was strongly correlated with the levels of PTH (r = 0.87, p < 0.01), but not with the total serum calcium levels (r = 0.04, NS). The decrease in intracellular calcium after parathyroidectomy was also strongly correlated with the decrease in PTH (r = 0.84, P < 0.01), but not with the decrease in total serum calcium (r = 0.16, NS). In the patients with essential hypertension, intracellular calcium correlated well with systolic (r = 0.69, p < 0.01), diastolic (r = 0.76, p < 0.01) and especially mean arterial pressure (r = 0.86, P < 0.01). There was no correlation between blood pressure and intracellular calcium in the patients with primary hyperparathyroidism. We conclude that normotensive patients with primary hyperparathyroidism, as well as patients with essential hypertension, can have increased concentrations of intracellular calcium in platelets. The correction of the hyperparathyroid condition normalizes intracellular calcium concentration. The close correlation between PTH and intracellular calcium suggests that PTH may act as a ionophore for calcium entry into cells. Whether the increased levels of intracellular calcium may reflect a pre-hypertensive condition in normotensive patients with primary hyperparathyroidism remains to be determined.     

A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension

OBJECTIVE: To compare the effectiveness of the combination of hydrochlorothiazide (HCT) plus sustained-release nifedipine with the combination of HCT plus reserpine in lowering high blood pressure (BP) unresponsive to HCT monotherapy. DESIGN: An open, randomised crossover drug trial. SETTING: Outpatients' clinic in Parirenyatwa Hospital, Harare, a tertiary referral centre. SUBJECTS: 32 Black patients of both sexes with newly diagnosed or previously treated hypertension aged between 21 and 65 years who had a BP > 140/95 after receiving HCT 25 mg daily for four weeks were studied. INTERVENTION: Patients were kept on HCT 25 mg daily and were randomised to receive either reserpine 0.25 mg daily or nifedipine (Adalat Retard) 20 mg bd for four weeks. This was followed by a two week washout period during which patients received HCT 25 mg daily only. After the washout period patients were crossed over to the alternative treatment for four weeks. Patients were kept on HCT 25 mg daily throughout the trial. MAIN OUTCOME MEASURES: The main outcome measure was the fall in BP which was taken as the difference between the BP at baseline and the BP at the end of each treatment period. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were taken. RESULTS: Both second line drugs were effective in lowering SBP and DBP and there was no significant difference between them. Nifedipine reduced SBP by 18.9 mmHg (95% CI 12.1 to 25.7) and DBP by 9.6 mmHg (95% CI 7.2 to 12.0). Reserpine reduced SBP by 15.9 mmHg (95% CI 8.4 to 23.4) and DBP by 11.1 mmHg (95% CI 7.5 to 14.6). However, only two patients attained the target DBP of < or = 90 mmHg after each active treatment period. CONCLUSION AND RECOMMENDATIONS: Since both agents were equally effective in reducing both SBP and DBP and reserpine is much cheaper than nifedipine, it is recommended that for a developing country like Zimbabwe, the combination of HCT and reserpine at the above doses should be used as the first step to treat mild to moderate hypertension without evidence of end organ damage. However, further trials should compare BP lowering effects as well as end organ protection offered by the trial drugs.     

Effect of 12-week treatment with amlodipine on plasma renin activity and adrenal cortex function in patients with essential hypertension

The present study aimed to assess the influence of 12-week treatment with Amlodipine (Am) on plasma renin activity (PRA), baseline and ACTH stimulated secretion of cortisol (C) and aldosterone (A). 21 patients with mild or moderately severe essential hypertension (EH) were examined. PRA was assessed under baseline and stimulatory conditions, C and A were estimated in blood samples withdrawn before (0') and 30, 60, 90, 120, 150, 180 minutes after i.v. administration of 0.25 mg of Synacthen. All parameters were performed twice: before and after 12-week treatment with 5-10 mg/d of Am. The control group (not treated with Am) consisted of 15 healthy volunteers. In EH patients PRA was significantly higher after 12 weeks of Am administration. Patients with EH before Am treatment showed a reduced response of C and A secretion to Synacthen as compared with controls, which became normalized after Am treatment. CONCLUSIONS: 1. Patients with EH are characterized by reduced response of C and A secretion to ACTH. 2. 12-week treatment with Am exerts a stimulatory effect on Synacthen induced C and A secretion and PRA in EH patients.     

Autonomic nervous system activity in essential hypertension: a comparison between dippers and non-dippers

This study examines whether race is a significant determinant of the diagnoses of acute myocardial infarction or angina pectoris in patients with symptoms suggestive of acute cardiac ischemia. The study population was comprised of 3401 (34%) African-American and 6600 (66%) white patients who presented to emergency departments with symptoms suggestive of acute cardiac ischemia. The main outcome measure was a diagnosis of acute myocardial infarction or angina pectoris. African Americans were younger, predominantly female, and more often had hypertension, diabetes mellitus, or smoked. The diagnosis of acute myocardial infarction was confirmed in 6% of African-American and 12% of white men, and in 4% of African-American and 8% of white women. After adjusting for age, gender, medical history, signs and symptoms, and hospital, African Americans were half as likely to develop acute myocardial infarction and were 60% as likely to have acute cardiac ischemia. Despite having less acute cardiac ischemia, African Americans in this study had high risk levels for coronary artery disease.     

Microalbuminuria in essential hypertensives in treatment for hypertension

Urinary albumin excretion (UAE) was evaluated in 26 subjects with essential hypertension and no diabetes (5 men, 21 women; 19 whites and 7 blacks), with creatinine clearance (Ccreat) > or = 75 ml/min/1.73 m2, in individualized treatment with various antihypertensive drugs. Clinical and laboratorial data were the following: mean age, 53 +/- 2 years (SEM); duration of hypertension, 14.9 +/- 2.2 years; body mass index (BMI), 26.8 +/- 0.7; arterial blood pressure, 142 +/- 4/89 +/- 3 mmHg; serum creatinine, 0.8 +/- 0.03 mg/dL; Ccreat, 99.3 +/- 3.8 ml/min/1.73 m2 and UAE, 9.3 +/- 1.5 micrograms/min. No significant difference was found when data were evaluated for gender and race. Microalbuminuria, defined as UAE > 13.9 micrograms/min, was found in 19% of the hypertensives (range: 16.3 to 28.1 micrograms/min). UAE correlated positively and significantly with systolic (r = 0.6309; P = 0.0005), diastolic (r = 0.4146; P = 0.0352), and mean blood pressure (r = 0.5000; P = 0.0093). The correlation between UAE and systolic pressure was stronger than with diastolic pressure. There was a positive and significant correlation between BMI and UAE values (r = 0.5623; P = 0.0028), and between BMI values with those of systolic (r = 0.5271; P = 0.0057) and mean blood pressure (r = 0.3930; P = 0.470). No correlation was found between UAE and age, duration of hypertension or Ccreat. Systolic, diastolic and mean blood pressures were significantly higher in microalbuminuric than in non microalbuminuric hypertensives. Obese hypertensives presented higher mean values of UAE, systolic, diastolic and mean pressures than non obese.     

Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension

The efficacy and tolerability of extended-release felodipine (felodipine-ER) and nifedipine gastrointestinal therapeutic system (nifedipine GITS) were compared in a multicenter, prospective, open-label clinical trial of 277 patients with mild-to-moderate uncomplicated essential hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 and < or = 115 mm Hg). After a 3-week washout period, patients were randomized to receive felodipine-ER (5 mg once daily) or nifedipine GITS (30 mg once daily); during a subsequent 6-week titration phase, the once-daily felodipine-ER dose could be increased to 10 mg and the nifedipine GITS dose to 60 or 90 mg in an attempt to achieve adequate blood pressure response (SiDBP < or = 90 mm Hg, or < 100 mm Hg with a > 10-mm Hg reduction from baseline, as measured 24 hours after dosing [trough]). At the end of titration, the mean daily doses of felodipine-ER and nifedipine GITS were 8 and 50 mg, respectively. Mean changes in sitting systolic blood pressure (SiSBP)/SiDBP were -14/-12 and -16/-13 mm Hg, respectively. All reductions were significant when compared with baseline (P < 0.01), but there were no significant differences between treatment groups. Adequate blood pressure response occurred in 77% of the felodipine-ER group and 80% of the nifedipine GITS group; this difference was not significant. Blood pressure changes were similar among sex and race subgroups. A higher percentage of older patients (> 55 years of age) than younger patients (< or = 55 years of age) reached goal SiDBP with both drugs. Patients with adequate SiDBP response continued receiving their assigned medication for an additional 6-week maintenance period. Reductions in SiDBP and SiSBP from baseline continued to be significant in both treatment groups. No clinically important changes in heart rate were noted. A total of 28 patients (15 in the felodipine-ER group and 13 in the nifedipine GITS group) withdrew from the study because of inadequate blood pressure response. At least one adverse experience occurred in 55% of the felodipine-ER group and 63% of the nifedipine GITS group, prompting withdrawal of 14 patients (10%) and 16 patients (11%), respectively. Headache and edema were the most common adverse experiences. The incidence and pattern of adverse experiences did not differ significantly between treatments. The results of this study demonstrate that once-daily felodipine-ER and nifedipine GITS are similarly highly effective and generally well tolerated in patients with essential hypertension.     

An approach to the treatment of essential hypertension

The efficacy and side effects of the combined administration of propranolol and phenoxybenzamine were examined in 19 patients with moderate and moderately severe essential hypertension. By titrating the dosage of both drugs against pulse rate and blood pressure response, propranolol was given between 80 and 160 mg. and phenoxybenzamine between 20 and 50 mg. per day in divided doses. There was a substantial reduction in both systolic and diastolic blood pressure in both recumbent and upright positions without orthostatic hypotension. Normal blood pressure (140/90 mm. Hg or less) or near normal (150/100 mm. Hg or less) was attained in 14 of the patients in the recumbent and 17 in the upright position. Pulse rate also decreased significantly, whereas body weight increased but not significantly so. Except for a reduction of ejaculation in three out of six male subjects, no symptomatic side effects were detected, and no changes in the liver or renal function or in blood count were observed. Despite the short duration of therapy, 3 to 10 weeks, this study clearly demonstrates that propranolol and phenoxybenzamine given together in individualized doses are very effective in lowering arterial blood pressure with minimal side effects.     

Comparative study to assess the efficacy and adverse effects of amlodipine and nifedipine retard in patients with stable exertional angina and hypertension

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.     

Efficacy and safety of enalapril versus extended-release nifedipine for the treatment of mild-to-moderate essential hypertension: a multicenter 22-week study. Multicenter Cooperative Study Group

The antihypertensive effects and tolerability of single daily doses of enalapril and extended-release nifedipine (nifedipine-ER) were compared in an open-label, randomized, parallel-group, 22-week treatment study involving 230 men and women (mean age, 55 years). Following a 3-week washout period, mean +/- SD blood pressure levels were 153 +/- 17/99 +/- 4 mmHg in the enalapril group (n = 117) and 157 +/- 17/100 +/- 5 mmHg in the nifedipine-ER group (n = 113). Beginning at 5 mg once daily for enalapril and 30 mg once daily for nifedipine-ER, the dosage was titrated every 4 weeks for 16 weeks, up to a maximum of 40 mg for enalapril and 120 mg for nifedipine-ER. The treatment goal (satisfactory response) was to lower trough sitting diastolic blood pressure to < 90 mmHg or by at least 10 mmHg to a level of < 100 mmHg. At a mean daily dose of 16 mg of enalapril and 57 mg of nifedipine-ER, more than three quarters of each treatment group achieved a satisfactory response. The mean reductions in trough sitting blood pressure levels at the end of 22 weeks of treatment were 15/11 mmHg for enalapril and 21/13 mmHg for nifedipine-ER. The difference between treatments was significant only for the change in systolic blood pressure (P < 0.05). However, enalapril was better tolerated than nifedipine-ER. The numbers of patients with adverse experiences and withdrawals from the study because of an adverse experience were significantly lower for enalapril than for nifedipine-ER (P < 0.05). The incidence of abnormal laboratory findings was small and considered of no clinical importance in either group. These data suggest that enalapril and nifedipine-ER had approximately equal efficacy as once-daily antihypertensive treatments, but enalapril was better tolerated.     

Circadian variation of haemodynamics in patients with essential hypertension: comparison between early morning and evening

OBJECTIVE: An increased incidence of cardiovascular accidents in the morning has been reported, but the reason why is not clear. We measured 24-h haemodynamics and focused on its change in the morning. DESIGN: To study the circadian variation of haemodynamics, we recorded 24-h direct blood pressure and electrocardiogram using a telemetry method, in 21 untreated inpatients with essential hypertension, and measured cardiac output using the dye-dilution method in the morning, in the evening and during sleep. We also determined the beat-to-beat cardiac output (using the pulse-contour method), the total peripheral resistance and the ratio of low- to high-frequency components (using power spectral analysis of the R-R interval during 24 h), and made comparisons between morning and evening values. RESULTS: Both systolic and diastolic blood pressure increased rapidly in the early morning. Although the comparison of blood pressure between morning and evening showed no difference, total peripheral resistance and low- to high-frequency ratio were significantly higher in the morning than in the evening, but cardiac output was lower in the morning. CONCLUSIONS: Sympathetic nervous activity and vascular resistance seem to be higher in the morning than in the evening, and these haemodynamic changes may stress the cardiovascular system.     

-Efficacy and safety of using amlodipine in treatment of mild and moderate essential hypertension-

The present study aimed to assess the efficacy and tolerance of amlodipine (Norvasc-Pfizer) in the treatment of 152 patients with mild and moderate essential hypertension. This study was a multicenter and open trial and lasted 24 weeks. During 7 visits arterial blood pressure, heart rate, body weight and side effects of amlodipine were registered. The dosage of amlodipine was 5 to 10 mg/day. 59 patients received also other antihypertensive drugs in doses used before starting amlodipine treatment. 57 patients needed changes in amlodipine dosing from 5 to 10 mg/day. During the study no significant changes in body weight or heart rate were noticed. Mean arterial blood pressure dropped significantly from 123.9 +/- 0.6 at the beginning of the study to 102.3 +/- 0.8 mm Hg at the end of this study. During this study a total of 26 dropouts were noticed. The reasons of these dropouts were the following: side effects--6 patients, noncompliance--7 patients, insufficient hypotensive effect--7 patients, unknown reason--5 patients, hypertensive crisis--1 patient. The following side effects were observed ocdemata of the legs in 10.5%, headaches in 2% of patients. One patient complained of increased susceptibility to weather changes, 1 patient had nausea and dizziness and 1 had headaches, pains in the legs and chest and nausea. All these side effects were mild and transient. Conclusion: Results obtained in this trial suggest, that amlodipine is an efficient and well tolerated antihypertensive drug in patients with mild and moderate essential     

Biobehavioral approaches to the treatment of essential hypertension.

Despite recent advances in the medical management of hypertension, chronically elevated blood pressure remains a major health problem in the United States, affecting almost 50 million Americans. It is widely recognized that lifestyle factors contribute to the development and maintenance of elevated blood pressure. This article critically reviews current approaches to the nonpharmacological treatment of high blood pressure and highlights outcome studies of exercise, weight loss and dietary modification, and stress management and relaxation therapies. Methodological issues in the assessment and treatment of hypertension are discussed, along with possible mechanisms by which lifestyle modification may reduce elevated blood pressure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The changes of intraerythrocyte calcium metabolism and their responses to nifedipine in patients with essential hypertension

Seven patients with open angle glaucoma were treated using Dorsolamida twice daily together Betablocant treat. Five patients with secondary glaucoma were treated with Dorsolamida three time daily as well three patients with edematous postimplant keratopathy. Intraocular pressure decreased with an average of 3-4 mm Hg and at the patients with corneal edema that decreased.