Antihypertensive effect of low-frequency transcutaneous electrical nerve stimulation (TENS) in comparison with drug treatment.

Hypertension is a major risk factor for vascular disease, yet blood pressure (BP) control is unsatisfactory low, partly due to side-effects. Transcutaneous electrical nerve stimulation (TENS) is well tolerated and studies have demonstrated BP reduction. In this study, we compared the BP lowering effect of 2.5 mg felodipin once daily with 30 min of bidaily low-frequency TENS in 32 adult hypertensive subjects (mean office BP 152.7/90.0 mmHg) in a randomized, crossover design. Office BP and 24-h ambulatory BP monitoring (ABPM) were performed at baseline and at the end of each 4-week treatment and washout period. Felodipin reduced office BP by 10/6 mmHg (p <0.001 respectively) and after washout BP rose to a level still significantly lower than at baseline. TENS reduced office BP by 5/1.5 mmHg (p <0.01, ns). After TENS washout, BP was further reduced and significantly lower than at baseline, but at levels similar to BP after felodipin washout and therefore reasonably caused by factors other than the treatment per se. ABPM revealed a significant systolic reduction of 3 mmHg by felodipin, but no significant changes were noted after TENS. We conclude that our study does not present any solid evidence of BP reduction of TENS.

[Therapeutic effect on essential hypertension treated with combined therapy of acupuncture and medication].

OBJECTIVE: To explore the mechanism of acupuncture combined with medication for treatment of essential hypertension (EH). METHODS: Sixty cases of EH were randomly divided into a combined acupuncture and medication group (group A) and a medication group (group B), 30 cases in each one, treated with acupuncture in combination with oral administration of Felodipine, and simple oral administration of Felodipine respectively. Before and after treatment, the changes of blood pressure, and the contents of E-selectin (Es), iNOS and eNOS were determined. RESULTS: After treatment, the blood pressure declined in either group. The total effective rate in group A was 86.7% (26/30), which was superior to that of 73.3% (22/30) in group B. After treatment, the plasma Es and iNOS contents in two groups decreased as compared with those before treatment (both P < 0.01), of which, plasma Es content in group A decreased apparently as compared with group B (P < 0.01). After treatment, the content of plasma eNOS increased as compared with that before treatment in group A (P < 0.01). CONCLUSION: The mechanism of acupuncture on anti-blood pressure probably relies on the improvements in vascular endothelial cellular function so that Es, iNOS and eNOS expression can be recovered to normal level and ultimately blood pressure is adjusted.

Felodipine reduces cardiac expression of IL-18 and perivascular fibrosis in fructose-fed rats.

Metabolic syndrome is associated with accelerated macrovascular and microvascular coronary disease, cardiomyopathy, and elevated inflammatory status. To determine whether metabolic syndrome-associated elevation of the inflammatory cytokine interleukin-18 (IL-18) in serum and cardiac tissue, and its potential sequelae could be attenuated pharmacologically, we studied fructose-fed rats. The fructose-fed rats exhibited increases in systolic blood pressure (SBP), body weight, heart weight, left ventricular weight, and blood insulin. Serum IL-18 levels in these rats were also elevated significantly. These changes were significantly different compared to those in control rats. Perivascular fibrosis around coronary arterioles was evident in the fructose-fed rats, accompanied by a paralleled increase in IL-18 by immunohistochemical analysis and real time polymerase chain reaction. Felodipine attenuated the increased levels in serum IL-18 and cardiac IL-18 mRNA as well as coronary perivascular fibrosis. Thus, augmented IL-18 in serum and cardiac tissue in metabolic syndrome may contribute to the coronary perivascular fibrosis; felodipine administration can attenuate the inflammatory and fibrosis process.

A review of calcium channel antagonists in the treatment of pediatric hypertension.

All children aged > or = 3 years should have an annual blood pressure (BP) measurement taken during a routine physical examination. Physicians should become familiar with recommended pediatric normative BP tables. BP above the 95th percentile may require drug therapy. There are several categories of antihypertensives available to the clinician. Calcium channel antagonists (CCAs) are a class of drugs that exert their antihypertensive effect by inhibiting the influx of calcium ions across the cell membranes. This results in dilatation of peripheral arterioles. When given orally, CCAs are metabolised in the liver by cytochrome P450 (CYP) enzyme CYP3A4; hence, some CCAs will affect the half-life of drugs that share this enzyme system for their metabolism. CCAs can be safely used in children with renal insufficiency or failure and as a general rule there is no need to modify drug dosage in this population. CCAs are generally well tolerated; most adverse effects appear to be dose related. Headache, flushing, gastrointestinal upset, and edema of the lower extremities are the most common symptoms reported with the use of CCAs. Pediatric data regarding safety and efficacy of CCAs have mostly been obtained from retrospective analyses. Extended-release nifedipine and amlodipine are the two most commonly used oral CCAs in the management of pediatric hypertension. These drugs can be given once a day, although many children require twice-daily administration. Extended-release nifedipine has to be swallowed whole; hence, its use in younger children who cannot swallow pills is limited. Amlodipine can be made into a solution without compromising its long duration of action; therefore, it is the CCA of choice for very young children. Oral short-acting nifedipine and intravenous nicardipine are safe and effective CCAs for the management of hypertensive crisis in children. Short-acting nifedipine can cause unpredictable changes in BP; hence, it should be used cautiously and in low doses. Intravenous nicardipine has a rapid onset of action and a short half-life. Intravenous infusion of nicardipine can be titrated for effective control of BP. Intravenous nicardipine has been used safely in hospitalized children and newborns for the management of hypertensive crisis, and for controlled hypotension during surgery. CCAs are a class of antihypertensives that are safe and effective in pediatric patients. They have relatively few adverse effects and are well tolerated by children. This article reviews CCAs as antihypertensives in the management of pediatric hypertension.

Comparative study of barnidipine and felodipine in Chinese patients with essential hypertension.

This study evaluated the efficacy and safety of barnidipine for the treatment of mild-to-moderate essential hypertension in Chinese patients. A total of 131 patients were randomized to receive either barnidipine (10 -15 mg) or felodipine (5 - 10 mg) once daily for 4 weeks. Both drugs reduced blood pressure significantly, with > or = 87% of patients obtaining a marked or moderate effect. The mean +/- SD reductions in systolic and diastolic blood pressure were 19.2 +/- 13.6 and 14.4 +/- 7.0 mmHg, respectively, for barnidipine treatment, and 20.3 +/- 11.3 and 14.7 +/- 7.7 mmHg, respectively, for felodipine treatment. There were no significant differences between the two drugs in terms of anti-hypertensive effect, heart rate, laboratory test results or incidence of adverse events. More patients taking felodipine experienced palpitations, but this difference was not statistically significant. Barnidipine is as efficacious and safe as felodipine in the treatment of essential hypertension in Chinese patients.

A factorial study of combination hypertension treatment with metoprolol succinate extended release and felodipine extended release results of the Metoprolol Succinate-Felodipine Antihypertension Combination Trial (M-FACT).

BACKGROUND: Many hypertensive patients require combination therapy to achieve target blood pressure (BP). beta-Blockers and dihydropyridine calcium channel blockers are effective as monotherapy in hypertensive patients and have complementary mechanisms for lowering BP. METHODS: This multicenter, randomized, placebo-controlled, unbalanced factorial study included a 4- to 5-week single-blind placebo, 9-week, double-blind treatment as well as a 2-week double-blind, down-titration period. Patients (N = 1092) were randomized to one of 16 treatment groups: extended-release (ER) metoprolol succinate (25, 100, or 400 mg), ER felodipine (2.5, 10, or 20 mg), ER felodipine/ER metoprolol succinate (2.5/25, 2.5/100, 2.5/400, 10/25, 10/100, 10/400, 20/25, 20/100, or 20/400 mg), or placebo. RESULTS: At baseline, treatment groups were well balanced; mean sitting BP was 152.6/99.9 mm Hg. Monotherapy with ER metoprolol succinate induced dose-related reductions in sitting systolic/diastolic BP (DBP) (mean 8.1/7.7 to 9.7/11.1 mm Hg) as did ER felodipine (mean 7.7/7.7 to 14.0/11.8) and the combinations reflected additive effects (mean 13.8/11.0 to 19.8/15.2). The decline in the placebo group was 2.1/4.0 mm Hg. All combinations were more effective than their components (P < .05 for all but ER metoprolol succinate 25/ER felodipine 20). When compared with the highest doses of the individual agents (ER metoprolol succinate 400 mg; ER felodipine 20 mg), the low-dose combination ER metoprolol succinate 25/ER felodipine 2.5 was approximately as effective (differences in DBP <1 mm Hg). The most common adverse events leading to discontinuation were peripheral edema (4%), headache (2%), and fatigue (1%). Higher rates of peripheral edema and flushing were associated with high-dose ER felodipine, either alone or in combination. CONCLUSIONS: The antihypertensive effects of ER metoprolol succinate and ER felodipine are dose-related, and when given in combination, their BP-lowering effects are additive over a wide dose range. Low-dose combination therapy is comparable in effectiveness to high-dose monotherapy but is better tolerated.

[Efficacy and tolerability of felodipine based antihypertensive therapy in hospitalized patients with hypertension]. / Effektivnost' i perenosimost' antigipertenzivnoi terapii, osnovannoi na felodipine, u bol'nykh arterial'noi gipertoniei v usloviiakh statsionara.

AIM: To compare efficacy and tolerability of felodipine based antihypertensive therapy with those of standard hospital treatment of hypertension. MATERIAL: Inhospital patients were randomized 1:2 to standard antihypertensive therapy or to therapy which included felodipine (n=50 and 100, 36 and 35% men, mean age 66.0+/-8.4 and 64.3+/-8.1 years, initial blood pressure 162.4+/-9.3/99.3+/-6.4 and 163.2+/-10.3/98.2+/-6.5 mm Hg, respectively). Felodipine was used: (1) as first drug with subsequent addition of other drugs as required; (2) after cessation of previously ineffective therapy; (3) in cases of intolerance to previous therapy, (4) as supplementation to previously insufficiently effective therapy. Results. At discharge in felodipine group 6, 25, 29 and 40% of patients received mono- (felodipine 10 mg/day), 2, 3 and 4 component therapy, respectively. In standard treatment group all patients received combination therapy with 3 (48%) or 4 (52%) drugs. Felodipine group compared with group of standard therapy was characterized by less frequent correction of antihypertensive therapy (0.8+/-0.6 and 2.2+/-0.9, p<0.05), smaller number of drugs used (3.03+/-0.95 and 3.52+/-0.5, p<0.01), more frequently achievement of target blood pressure level (88 and 64%, p=0.0075), less pronounced difference between morning and evening self-measured blood pressure. CONCLUSION: The use of felodipine in hospitalized patients with hypertension allowed achieving target blood pressure with fewer drugs. Felodipine was safe and well tolerated.

Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercanidipine in Adults (LEAD) Study.

This multicenter, double-blind, parallel-group study compared the effects of three dihydropyridine calcium channel blockers (lercanidipine, felodipine, and nifedipine gastrointestinal therapeutic system) on blood pressure and heart rate in 250 patients with mild to moderate hypertension (diastolic blood pressure > or =95 and 109 mm Hg). Patients were randomized to 4 weeks of treatment with once-daily doses of lercanidipine 10 mg, felodipine 10 mg, or nifedipine gastrointestinal therapeutic system 30 mg. After 4 weeks of treatment, the dose was doubled in nonresponding patients. At 8 weeks, no significant differences in blood pressure were observed among the three groups. Increases in heart rate in all three groups induced by stressful conditions before and after treatment were not exacerbated during active treatment. The incidence of adverse drug reactions was lower in the lercanidipine and nifedipine groups than in the felodipine group (p<0.05); in particular, the incidence of edema for lercanidipine was 5.5% vs. 13% for felodipine and 6.6% for nifedipine.

Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients.

The efficacy and safety profiles of barnidipine in the treatment of hypertension were evaluated in an open parallel-group study. Fifty-nine Chinese patients with mild-to-moderate essential hypertension were randomized to receive either barnidipine or felodipine (5 mg once daily, titrated to 10 mg or 15 mg once daily, as indicated) for 12 weeks. Both drugs reduced blood pressures significantly with > or = 68% of cases obtaining marked or moderate blood pressure reduction. Mean reductions in systolic and diastolic blood pressure for barnidipine treatment were 23.7 +/- 13.5 mmHg and 12.7 +/- 7.9 mmHg, and for felodipine, 24.3 +/- 18.4 mmHg and 14.5 +/- 10.0 mmHg, respectively. There was no significant difference between these two drugs in anti-hypertensive effect, heart rate, laboratory measurements or incidence of adverse events. The only difference was that more patients taking felodipine experienced palpitations. We conclude that barnidipine has similar efficacy and a similar safety profile to felodipine in the treatment of mild-to-moderate essential hypertension in Chinese patients.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

BACKGROUND: Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. OBJECTIVE: The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. METHODS: A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. RESULTS: Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. CONCLUSIONS: Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination of amlodipine/ benazepril can be successfully accomplished in the majority of patients.

A randomised trial to compare the efficacy and safety of Felodipine (Plendil) and Nifedipine (Adalat) retard in patients with mild-to-moderate hypertension.

The efficacy and tolerability of Felodipine extended-release was compared with Nifedipine retard in the management of patients with mild-to-moderate hypertension. A total of one hundred and thirty three patients were screened out of which one hundred and twenty-one patients were enrolled in a 9-week multicentre open, randomised rising-dose trial to receive either Felodipine 5-10 mg once daily or Nifedipine 10-20 mg twice daily. Blood pressure was measured at the end of the dosing interval that is 24 hours and 12 hours after Felodipine and Nifedipine respectively. Both drugs, Felodipine and Nifedipine were found to lower blood pressure significantly compared with baseline. After three weeks of treatment, seated blood pressure was reduced by 20/14 mmHg (systolic/diastolic) and by 24/16 mmHg after 6 weeks in the felodipine group. Corresponding values in the Nifedipine group were 16/09 mmHg and 24/13mmHg. Pulse rate was not significantly affected by either drugs. The percentage of patients who had satisfactory control after 3 weeks treatment was 57.6% for Felodipine and 33.3% for Nifedipine (significant). After dose titration (where necessary), at the end of the study the response rates were 76.3% (n=45) and 79.6% (n=43) for Felodipine and Nifedipine respectively (non significant). Both drugs were metabolically inert and did not derange the haematologic and biochemical profile of patients. They produced no significant weight changes. The pattern of side effects were similar in both groups but tended to be more severe with Nifedipine necessitating withdrawal of two patients in this group. In conclusion, Felodipine ER 5mg - 10mg once daily, and Nifedipine Retard, 20mg twice daily were equally effective medications for mild-to-moderate hypertension but Felodipine was better tolerated.

A randomized prospective crossover trial of amlodipine in pediatric hypertension.

Amlodipine has potential advantages in children since it can be dissolved into a liquid preparation and has a long elimination half-life, allowing for once-daily administration. The objective of this study was to compare the efficacy and compliance of amlodipine with that of standard long-acting calcium channel blockers (felodipine or nifedipine) in hypertensive children. A randomized, prospective, crossover study of 11 hypertensive children (9-17 years of age, 10 renal transplant patients) was performed with electronic monitoring of compliance. Each treatment arm was 30 days. No significant differences were observed in mean systolic (SBP) and diastolic blood pressures (DBP) between amlodipine and the other calcium channel blockers. Using 24-h blood pressure monitoring there were no significant differences over each drug treatment period in both mean day-time and night-time SBP and DBP. Patient compliance was similar in both the amlodipine and the nifedipine/felodipine treatment periods. These data suggest that amlodipine is as effective in pediatric nephrology patients as nifedipine and felodipine. Amlodipine may be optimally suited for treatment of young children because at present it is the only calcium channel blocker which can be administered once daily as a liquid preparation.

Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats.

Natural products like pumpkin-seed oil (PSO) may modify the potency of the calcium antagonist felodipine (FEL) or angiotensin-converting enzyme inhibitor (ACE-inhibitor), captopril (CPT) in modulating the biochemical derangement in blood, heart and kidney as well as blood pressure and heart rate of spontaneously hypertensive rats (SHR) were investigated. SHR were treated orally with FEL at a dose of 0. 45 mg kg(-1) body wt. or CPT at a dose of 9 mg kg(-1) body wt. once daily for 4 weeks. PSO was administered at a dose of 40 mg kg(-1) body wt. alone or with FEL or CPT in the previous respective dose regimen for the same period to SHR. This study showed that hypertension induced increments the content of malondialdehyde (MDA) by 55% and 38% as well as the activity of glutathione peroxidase (GSH-Px) by 26% and 23% in heart and kidney, respectively, accompanied by reductions in the activity of myocardial superoxide dismutase (SOD) from 3.40+/-0.17 to 2.42+/-0.19 U mg protein(-1)and contents of glutathione (GSH) and protein thiols (PrSHs) in different tissues of SHR as compared to normotensive rats. Treatment of SHR with FEL or CPT monotherapy or combined with PSO produced improvement in the measured free radical scavengers in the heart and kidney. Our results also showed that pretreatment of SHR with PSO for 4 weeks then i.v. administration of FEL or CPT produced a significant beneficial hypotensive action. The results were explained in the light of the antioxidant properties of PSO. Therefore, it is concluded that concomitant administration of FEL or CPT with natural antioxidants can yield a beneficial therapeutic effect and retard the progression of hypertension.

Rational use of calcium-channel antagonists in Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a peripheral circulatory disorder characterized by sudden episodes of digital artery spasm, often precipitated by cold temperature or emotional stress. Although the cause of RP is not fully known, it appears to involve inappropriate adrenergic response to cold stimuli. Treatment of RP is conservative in most patients, but in patients with severe disease includes the use of agents that promote digital vasodilation. The calcium-channel antagonists, particularly the dihydropyridine derivative nifedipine, are the most thoroughly studied drug class for the treatment of RP. Approximately two thirds of patients respond favorably, with significant reductions in the frequency and severity of vasospastic attacks. Nifedipine use is often limited by the appearance of adverse vasodilatory effects such as headache or peripheral edema. The newer second-generation dihydropyridines such as amlodipine, isradipine, nicardipine, and felodipine also appear to be effective in patients with RP and may be associated with fewer adverse effects.

A comparison of nisoldipine coat-core and felodipine in the treatment of mild-to-moderate hypertension.

The efficacy and safety of nisoldipine CC and felodipine were compared in a multicentre, randomised, double-blind, trial in patients with mild-to-moderate hypertension (n = 229). Following a two-week placebo run-in period, patients were randomised to 16 weeks' active treatment with nisoldipine coat core (CC) 20-40 mg or felodipine 5-10 mg once daily. At week 16, a higher proportion of patients in the nisoldipine CC group were on low-dose therapy (51% vs 36%, p = 0.07). The proportion of treatment responders was 77.8% with nisoldipine CC and 66.5% with felodipine. The mean change from baseline in systolic/diastolic blood pressure was -18.8/-13.6 mmHg with nisoldipine CC and -17.4/-11.3 mmHg with felodipine. The most common adverse events included peripheral oedema and headache; neither treatment affected heart rate. Thus, nisoldipine CC and felodipine provide comparable antihypertensive efficacy. The adverse effects of both drugs are related to their vasodilator properties and are common to the class.

A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine.

OBJECTIVE: A clinical definition of a hypertensive emergency is excessively high blood pressure in the presence of symptoms indicating end organ damage. Equally high blood pressure without symptoms is called a hypertensive crisis. Patients with hypertensive crisis or emergency need prompt, effective, and specific therapy and a controlled reduction of blood pressure. METHODS: We performed a randomized, double-blind multi-centre study, to compare the safety, efficacy and tolerability of an intravenous (i.v.) infusion of two dihydropyridine calcium channel blockers (either nifedipine or felodipine) in 122 patients, of whom 63 were diagnosed as hypertensive emergencies and 59 as hypertensive crisis, who had not reacted adequately (diastolic blood pressure <115 mmHg) to 5 mg of nifedipine PO. RESULTS: Both drugs lowered blood pressure adequately in more than 90% of the patients and were well tolerated. Only one patient had to be withdrawn, because of an excessive decrease in blood pressure. CONCLUSION: Patients with excessively high blood pressure who do not react to oral nifedipine can be treated equally effectively with felodipine and nifedipine IV. Felodipine is easier to handle because of its lack of light sensitivity.

Replacing short-acting nifedipine with alternative medications at a large health maintenance organization.

In response to recent evidence about the safety of calcium channel blockers, Group Health Cooperative of Puget Sound (GHC), a large health maintenance organization, implemented a plan in April 1996 to reevaluate the medications of 1349 patients who were taking short-acting nifedipine. Following the intervention, 79.8% of patients taking short-acting nifedipine discontinued use, and 45.6% switched to once-daily felodipine. By presenting physicians and patients with recent evidence about the safety of short-acting nifedipine, a large health maintenance organization was able to motivate broad-scale changes to safer alternative drug therapies.