Long term reduction in sodium balance: possible additional mechanism whereby nifedipine lowers blood pressure (original) (raw)
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Clinical science. Supplement (1979), 1982
1. Nifedipine (20 mg) was given by mouth to seven patients with moderate essential hypertension receiving a low, normal or high sodium intake. The drug produced an important hypotensive effect. Normal sodium intake enhanced the hypotensive action of the drug compared with that during the low and high sodium regimens. Blood pressure remained significantly lower 3 h after drug ingestion. 2. Increases in heart rate and plasma renin activity under all conditions reflected enhanced adrenergic activity. 3. A short-term natriuresis followed nifedipine ingestion in spite of increased aldosterone excretion during the low sodium diet and a decrease in urinary kallikrein during the low and high sodium diets. 4. Nifedipine increased urinary volume only during the high sodium intake. 5. Apart from vasodilatation, nifedipine induces important changes in neurogenic, renal and adrenal mechanisms that regulate blood pressure homoeostasis. Different conditions of sodium balance modulate most of these effects.
Nifedipine in the treatment of hypertension: report of a double-blind controlled trial
British Journal of Clinical Pharmacology, 1982
The effect of oral nifedipine has been examined in patients with hypertension in whom arterial pressure was not adequately controlled by the combination of a ,3-adrenoceptot antagonist (or a-methyldopa) and a diuretic. 2 In 42 patients, nifedipine (10 mg capsules) was added to the existing therapy in a final dose of 20-60 mg daily. Six patients had to stop the drug on account of side-effects. In the 36 patients who continued treatment, arterial pressure fell by an average of 24/9 mmHg supine and 26/10 mmHg standing. 3 In 11 of these patients who subsequently completed a double-blind, cross-over, placebo controlled trial, nifedipine (30-60 mg daily) was found to reduce arterial pressure by an average of 19/11 mmHg supine and 21/12 mmHg standing. 4 In all 11 patients who were changed to a sustained release preparation of nifedipine, control of arterial pressure was at least as good as it had been when taking the capsules.
Long-term therapy with slow-release nifedipine in essential hypertension
Cardiovascular Drugs and Therapy, 1990
The purpose of this study, designed as an open multicenter trial, was to test the antihypertensive efficacy, patient acceptability, and side effects of long-term treatment with slow-release nifedipine in a large population. The drug was studied in 330 outpatients with essential hypertension, WHO stage 1-2, recruited in 20 hospital centers. After washout period was completed, nifedipine (20 mg bid) was given for 1 month (phase 1). Then, the treatment was extended for 4 months (phase 2) with variable doses (range 20-80 mg daily). No other antihypertensive drugs were administered during phase 1. However diuretics, beta blockers, or captopril were added to nifedipine during phase 2 in 11 patients. Seventy patients did not meet criteria for inclusion at washout. During phase 1 and 2, 66 additional patients were excluded due to side effects, the need of other antihypertensive drugs, or noncompliance. Systolic blood pressure significantly lowered (10% or more) in 84% patients in phase 1 and in 76% in phase 2. No responders were 6.1% and 3.6~, respectively. Diastolic blood pressure was normalized in 60% of patients after 5 months of therapy. Effects on blood pressue were equal in young patients and in the .elderly, but a minimal rise in heart rate was recorded in younger patients. At least one side effect occurred in 46.6c~ patients, mainly headache (15.4%), hot flashes (13.3%), ankle edema (12.8G), or palpitation (6.6%). Sixteen patients (8.2~) were obliged to stop nifedipine treatment due to the severity of the side effects. This trial confirms the efficacy of nifedipine in hypertension, both in young and in aged patients. The adherence of patients to the twice-daily regimen was very good, without the development of tolerance in long-term treatment. The drug does not affect the physiologic cardiovascular response to standing, but induces several relatively common, very seldom severe, adverse reactions.
The American Journal of Cardiology, 1991
ifedipine has been extensively and successfully used for the treatment of various hypertensive syndromes in doses of > 10 mgl; such doses have a harmful potential, at least in the elderly.1-8 As there are only scant reports about the use of smaller doses of nifedipine,9~10 we undertook this clinical study to test the effectiveness and safety of a single 5-mg dose of oral nifedipine in patients admitted to our Emergency Care Department with uncontrolled moderate to severe hypertension. Only patients with essential hypertension were treated if the diagnosis had been present for 2 1 year and, if previously normotensive under medical treatment, they had a gradual elevation of the diastolic blood pressure (BP) to values from 110 to 129 mm Hg. Excluded were patients with coexisting valvular heart disease or acute myocardial infarction, those who were pregnant or who were receiving calcium antagonists within the previous 12 hours, or those with hypertensive urgencies and emergencies. Fifty-two consecutive patients (33 women and 19 men aged 31 to 70 years [mean f standard deviation 51 f Ill) full'lling the aforesaid criteria were treated. All underwent clinical history, physical examination, fundoscopy, electrocardiography at rest, chest roentgenography, and basic blood chemistry sampling. A monitor for continuous electrocardiographic display and intravenous 5% glucose in water were installed for safety reasons. Patients were divided into 2 groups: group A, diastolic BP from 110 to 119 mm Hg, and group B, diastolic BP from 120 to 129 mm Hg; 6 patients in group A and 7 in group B had signs of hypertensive heart disease on chest x-ray and on electrocardiography. In an open trial, all patients received a single 5mg dose of nifedipine by chewing a multipierced capsule. Heart rate and supine BP were recorded immediately before and 5, 15, 30, 45 and 60 minutes after drug ingestion and then every 30 minutes until minute 180. The same observers monitored all BP and heart From the Department of Emergency Care,
Nifedipine in hypertensive emergencies
BMJ, 1983
The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 22/126 14 mm Hg to 152 1 20/89 12 mm Hg after 30 minutes, p <0001). Heart rate increased from 74 11 to 84-+ 11 beats/minute (p<001); this effect was inversely related to age (r 0 65, p <0 01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment (r-=067, p <0 001 for systolic, and r-0-58, p <0 01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.