Long-acting Nifedipine Research Articles

Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction.

Blockade of bradykinin breakdown and enhancement of prostaglandin release probably participate in the antihypertensive activity of angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase blockers may attenuate the efficacy of ACE inhibitors by interfering with prostaglandin synthesis, and patients taking aspirin may not benefit from ACE inhibition. This study was designed to evaluate the incidence of the counteractive phenomenon and to define minimal aspirin dosage that causes an antagonistic effect. These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe untreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in group 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenuation of more than 20% of the mean blood pressure decrease produced by enalapril was the criteria that defined antagonism. The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: mean arterial pressure was lowered by 63% and 91% less, respectively. Results were independent of the drug administration order. In "responders," aspirin significantly attenuated the renin rise associated with ACE inhibition. These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardless of hypertension severity. Antagonism may be mediated through prostaglandin inhibition according to predominance, in an individual patient, of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.

Differential Activation of Cardiac and Peripheral Sympathetic Nervous System by Nifedipine: Role of Pharmacokinetics

Objectives. We sought to study the effects of short-acting and long-acting nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood pressure (BP) of normotensive subjects under baseline conditions and during SNS stimulation.Background. Calcium channel antagonists in different pharmacokinetic formulations are widely used in patients with coronary artery disease or hypertension. Short-acting formulations activate the SNS, an action that may be disadvantageous in patients with coronary disease, especially if left ventricular function is impaired. The effects of slow-release formulations on the SNS are unknown.Methods. We used microneurography to investigate the influence of nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy volunteers.Results. Peak plasma levels after short-acting and slow-release nifedipine were achieved within 60 min and 330 min, respectively. Short-acting (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly activated MSA and increased plasma norepinephrine; plasma endothelin increased only with slow-release nifedipine. HR increased after short-acting nifedipine, but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade of cardiac sympathetic activity (with esmolol) led to similar decreases in HR with or without nifedipine, whereas parasympatholysis (with atropine) led to similar increases in HR with or without nifedipine. The cold pressor test markedly increased MSA in all treatment groups and further increased MSA beyond the increase induced by nifedipine.Conclusions. Nifedipine markedly increased MSA, but not SSA, independently of drug release formulation. In contrast, HR increased with short-acting, but not with slow-release, nifedipine. Therefore, nifedipine activates cardiac and peripheral sympathetic nerves differently depending on pharmacokinetics. These effects of nifedipine may be disadvantageous in cardiac patients with increased sympathetic activity or congestive heart failure, or both.(J Am Coll Cardiol 1997;29:1607–14)

24-Hour Blood Pressure Profiles in Patients with Hypertension Treated with Amlodipine or Nifedipine GITS

An open crossover trial was conducted to compare the effects of 2 long-acting dihydropyridine calcium antagonists, amlodipine (5 to 10 mg/day) and nifedipine GITS (gastrointestinal therapeutic system) [30 to 60 mg/day], in 40 patients with mild to moderate essential hypertension. Particular attention was given to performance of the 2 drugs during the early morning hours. Each phase of treatment lasted 12 weeks. After an initial drug washout period (and at the end of each phase), 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) was performed. In addition, sphygmomanometric measurements were obtained at regular intervals during treatment.

Antihypertensive therapy debate: contribution from the Shanghai Trial Of Nifedipine in the Elderly (STONE).

In 1993, a number of influential bodies reported the results of consensus conferences on the management of hypertension, including the World Health Organization/International Society of Hypertension, the fifth United States Joint National Committee (JNC-V), the British Hypertension Society, the Canadian Hypertension Society (CHS) and the New Zealand National Advisory Committee. Most of these guidelines were in general agreement. The most significant difference was in the choice of first-line agents, whether to use only beta-blockers or thiazides (JNC-V/CHS) or to use any of the five major classes of antihypertensive agents. At present, this is the only placebo-controlled trial on newer classes of medications for which results are available. The trial has both strengths and weaknesses. Among the strengths of this trial is the comparability of the subjects in both arms and the robustness of the results. STONE does at least suggest that outcomes with newer agents like long-acting nifedipine are comparable to outcomes in major clinical trials in the elderly using diuretics and beta-blockers.

Implementation of local guidelines for cost-effective management of hypertension

To evaluate the effects of an intensive intervention to implement guidelines for cost-effective management of hypertension on medication use and cost, blood pressure control, and other resource use. Retrospective cohort trial based on the Cleveland Veterans' Affairs Medical Center Firm System. General internal medicine teaching clinic in a large university-affiliated Department of Veterans Affairs Medical Center. All patients seen in the intervention firm (n = 1273) and control firm (n = 884) clinics in the 3-month period following the introduction of the guidelines. The control firm received guidelines and usual education for the cost-effective outpatient management of hypertension. The intervention firm received guidelines plus intensive guideline-based education and supervision. The use of guideline medications was greater in the intervention firm as compared with the control. The intervention firm initiated more hydrochlorothiazide (HCTZ), 17.4% (95% confidence interval [CI] 14.8, 20.1) of patients versus 11.9% (CI 9.3, 14.8) in the control firm (p = .002). Atenolol was initiated in 7.2% (CI 5.6, 9.0) in intervention firm versus 4.7% (CI 3.2, 6.6) in the control (p = .03). In addition, the use of nonguideline medications was less in the intervention firm. The intervention firm initiated less long-acting nifedipine, 7.8% (CI 6.0, 9.8) versus 10.6% (CI 8.2, 13.5) in the control (p = .04). Blood pressure control demonstrated greater improvement in the intervention firm (p = .02). Use of guidelines was associated with decreased costs for antihypertensive medications in the intervention firm as a whole as compared with the control firm. There was no increased use in other measured resources in the intervention firm including the number of outpatient laboratory services obtained, clinic visits, emergency room visits, or hospitalizations. Intensive implementation of guideline-based education and supervision was associated with an increased use of guideline medications, decreased use of costly alternative agents, and no decrement in the measured outcomes of care.

Nifedipine and Intraoperative Core Body Temperature in Humans

Initial anesthetic-induced hypothermia results largely from core-to-peripheral redistribution of heat. Nifedipine administration may minimize hypothermia by inducing vasodilation well before induction of anesthesia. Although vasodilation would redistribute heat to peripheral tissues, thermoregulatory responses would maintain core temperature. After equilibration, the patient would be left vasodilated, with a small core-to-peripheral temperature gradient. Minimal redistribution hypothermia may accompany subsequent induction of anesthesia, because heat flow requires a temperature gradient. In contrast, similar vasodilation concurrent with anesthetic-induced vasodilation may augment redistribution hypothermia. Accordingly, the authors tested the hypothesis that nifedipine treatment for 12 h before surgery would minimize intraoperative redistribution hypothermia, whereas nifedipine treatment immediately before induction of anesthesia would aggravate hypothermia. Patients undergoing hip arthroplasty were randomly assigned to: (1) 20 mg long-acting nifedipine orally 12 h before surgery, and 10 mg sublingually 1.5 h before surgery (n = 10); (2) nifedipine 10 mg sublingually just before induction of anesthesia (n = 10); and (3) no nifedipine (control, n = 10). Anesthesia was maintained with isoflurane and 60% nitrous oxide. Administered intravenous fluids were heated, but the patients were not otherwise actively warmed. Core temperature decreased 0.8 degree C in the first hour of surgery in the patients given nifedipine the night before and the morning of surgery, which was significantly less than in the control group (1.7 degree C in the first hour). In contrast, core temperature decreased 2.0 degrees C in the first hour of surgery in the patients given nifedipine immediately before induction of anesthesia. During the subsequent 70-130 min of anesthesia, core temperature decreased at roughly comparable rates in each group. After 130 min of anesthesia, core temperature in the two nifedipine-treated groups differed by 1.6 degrees C, and the temperatures in all three groups differed significantly. Vasodilation induced by nifedipine well before induction of anesthesia minimized redistribution hypothermia, presumably by decreasing the core-to-peripheral tissue temperature gradient. In contrast, redistribution hypothermia was aggravated by administration of the same drug immediately before induction of anesthesia. Drug-induced modulation of vascular tone thus produces clinically important alterations in intraoperative core temperature.

Effects of long-acting nifedipine on casual office blood pressure measurements, 24-hour ambulatory blood pressure profiles, exercise parameters and left ventricular mass and function in black patients with mild to moderate systemic hypertension

Thirty-nine black patients with mild to moderate hypertension were treated for 1 year with various long-acting preparations of nifedipine, during which time serial changes in 24-hour ambulatory blood pressure (BP), exercise performance, left ventricular (LV) mass index and LV systolic function were evaluated. Mean 24-hour ambulatory BP decreased from 156 ± 15 99 ± 8 to 125 ± 10 79 ± 6 mm Hg at 1 year (p <0.0001). LV mass index decreased from 130 ± 40 to 114 ± 39 g/m 2 at 6 weeks (p <0.005) and to 95 ± 32 at 1 year (p <0.0001). There was a significant reduction in septal and posterior wall thickness from 11.0 ± 2.0 to 9.3 ± 2.0 mm (p <0.0001) and from 10.9 ± 2.0 to 9.3 ± 2.0 mm (p <0.005), respectively. Cardiac index and fractional shortening changed insignificantly from 2.9 ± 0.7 to 2.9 ± 0.6 liters/min/m 2, and from 35 ± 5 to 36 ± 6%, respectively. At 1 year, using a modified Bruce protocol, exercise time increased from 691 ± 138 to 845 ± 183 seconds (p <0.05); peak exercise and 1 minute post-effort systolic BP decreased from 240 ± 26 to 200 ± 21 mm Hg and from 221 ± 27 to 169 ± 32 mm Hg (p <0.05), respectively. It is concluded that in the treatment of black patients with mild to moderate hypertension, the marked and sustained antihypertensive action of long-acting nifedipine documented by 24-hour ambulatory BP monitoring is associated with LV mass regression with no adverse effect on cardiac function together with a reduction in exercise systolic BP and a prolongation of exercise time.

Clinical significance of ambulatory blood pressure monitoring. Evaluation of severity of hypertension, efficacy of treatment and effects on nighttime blood pressure.

Blood pressure (BP) obtained by the physician in his office and ambulatory BP recorded every hour throughout 24 hours with a noninvasive automated BP monitoring device were compared in 10 normotensives and 162 hypertensives. Casual BPs significantly correlated with averages in ambulatory BPs (ABPs) throughout the whole day, day (7 am - 10 pm) and night (0-5 am). However, it was noted that 6 of 10 normotensives and all of the moderate to severe hypertensives had ABPs of more than 150/90 mmHg at least once during the 24-hour period. The incidence of ABPs greater than 150/90 mmHg among all readings was higher in untreated and treated hypertensives with diastolic BPs in the office of more than 105 mmHg, and, when checked along with the clock time, higher not only in the morning but also in the evening. On the other hand, one-third or one-fifth of treated hypertensives with diastolic office BPs less than 90 mmHg or between 90 and 105 mmHg respectively had ABPs less than 150/90 mmHg throughout the whole day. When the effect of nicardipine (60 mg, t.i.d.) or slow-release nifedipine (27.3 +/- 3.0 mg, b.i.d.) on minimum BP during the night was analyzed, long-acting nifedipine decreased BP throughout the night to levels not significantly different from normotensive controls, whereas short-acting nicardipine did not affect nighttime BPs. These results suggest that simple ABP monitoring throughout the day gives us useful information to evaluate the severity of hypertension and the efficacy of antihypertensive medication as well as to avoid overtreatment with long-acting hypotensive agents resulting in a great fall in BP during sleep.

Nisoldipine: a replacement therapy for nifedipine in the treatment of severe hypertension.

The use of nisoldipine (10-20 mg b.i.d.) was evaluated as a replacement therapy for long-acting nifedipine (40-120 mg/day) in 21 patients with severe hypertension, who were resistant to or intolerant of nifedipine. Except for one patient with specific contraindications, all participants received an individually determined constant dose of beta blocker throughout the 8-month study. Results indicated a significant decrease in blood pressure after four weeks of treatment with nisoldipine (173 +/- 5/98 +/- 4 to 156 +/- 3/91 +/- 2 mmHg, p less than 0.05) without an associated change in pulse rate in 19 patients; only 5 of the 21 patients showed no further benefit from nisoldipine. No significant biochemical changes were noted in any of the patients during the study. In three patients, leg edema that had developed as a consequence of previous nifedipine therapy resolved completely following nisoldipine administration. Two patients withdrew from the study before term because of headaches and palpitations. An additional two patients suffered headaches, but tolerated the drug and continued the study. One patient suffered from polyuria. Nisoldipine appears to be an effective substitute treatment for nifedipine in severely hypertensive patients sensitive or resistant to nifedipine.

Long-acting nifedipine in moderate and severe hypertensive patients with serious concomitant diseases

Long-acting nifedipine tablets were given to 47 severely and moderately hypertensive patients with renal insufficiency, cardiovascular, cerebrovascular, and peripheral vascular disease, diabetes mellitus, asthma, and systemic lupus erythematosus. Nifedipine substituted vasodilators (n = 22), was added to beta blockers and thiazides (n = 14), and was used alone (n = 11). In all three groups blood pressure was significantly reduced without aggravation of angina pectoris, intermittent claudication, cerebrovascular disease, or renal failure. Side effects were mild and transient. We found nifedipine tablets convenient and safe, as well as efficacious in patients with serious conditions.

Long acting nifedipine in the treatment of severe hypertension

The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.