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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Today calcium antagonists (Ca-antagonists) are widely used agents in the management of various diseases of the circulatory system. More than 20 years ago the Ca-antagonists of the so-called 1st generation (Verapamil, Diltiazem, Nifedipine) were introduced for treatment of angina pectoris and later of essential hypertension. In the last decade an increasing number of agents structurally related to dihydropyridines were developed for the treatment of hypertension and/or coronary heart disease or cerebral disorders; the main target was to reduce side effects and to guarantee once or at least twice daily administration. Therefore the Ca-antagonists of the so-called 2nd generation (e.g. Amlodipine, Felodipine, Isradipine, Nitrendipine, Nicardipine, Nimodipine, Nisoldipine) tend to longer elimination-half-lives; Amlodipin is an exception with an elimination-half-life of 30 hours on the average. Apart from elimination rates, however, the biopharmaceutical and pharmacokinetic characteristics of all Ca-antagonists are similar: they are highly cleared drugs and are relatively highly protein bound. As they are subject to significant hepatic first-pass-metabolism old age and hepatic disease will increase their plasma-concentrations. Renal impairment affects little their pharmacokinetics since the fraction eliminated unchanged by the kidneys is small. For most agents, plasma-concentration-response relationships have been described. With exception of nicardipine a linear pharmacokinetic in all Ca-antagonists was demonstrated. Drugs and food affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. With regard to the acute pharmacodynamic effects the Ca-antagonists show similar qualitative effects, though there are quantitative differences. Orally administered dihydropyridine-derivatives induce acute hypotensive effects, whereas the other compounds show clinically relevant hypotensive effects only when administered chronically per os or less pronounced when given as intravenous infusion.
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PMID:[Principles of the pharmacokinetics and pharmacodynamics of calcium antagonists]. 813 31

Nisoldipine is a new calcium-channel blocker of the dihydropyridine subclass, with a chemical structure similar to nifedipine. It has been used in clinical trials to assess its efficacy and safety in patients with hypertension, angina pectoris, and congestive heart failure. Similar to other dihydropyridines, nisoldipine is a potent peripheral and coronary dilator. The most optimal dosage regimen has not been established in clinical trials. The drug appears to have a favorable side-effect profile.
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PMID:Nisoldipine: a new dihydropyridine calcium-channel blocker. 842 13

Twenty-eight patients (11 Caucasian, 17 black) whose blood pressure was more than 160/96 mmHg after 4 weeks on placebo added to atenolol 100 mg/day were randomly given, in addition, nisoldipine 10 mg or nifedipine 20 mg each twice a day for 8 weeks in a double-blind cross-over study. There was a statistically significant (P < 0.001) fall in blood pressure with no change in heart rate, both supine and erect, on both drugs. There were no significant differences between nisoldipine and nifedipine. Adverse effects were recorded in 15%, 17% and 35% of the patients available for safety comparison for placebo, nisoldipine and nifedipine, respectively. There were no significant differences between the black and Caucasian patients in blood pressure responses, although the study had only a low power to detect these. However, the fasting serum triglyceride levels at the end of both calcium antagonist treatment periods were highly significantly lower in the black patients compared with the Caucasian patients. Nisoldipine, which has a higher coronary vascular selectivity and less negative inotropism than nifedipine, is as effective and as well tolerated as nifedipine in patients whose hypertension is inadequately controlled on atenolol. It may have a special role in hypertensive patients with impaired left ventricular function.
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PMID:Comparison of nisoldipine and nifedipine as additional treatment in hypertension inadequately controlled by atenolol. 850 91

Nisoldipine (Sular-Zeneca), a dihydropyridine calcium-channel blocker structurally similar to nifedipine, has been approved for marketing by the US Food and Drug Administration. It is available in an oral extended-release formulation for treatment of hypertension.
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PMID:Nisoldipine--a new calcium channel blocker for hypertension. 859 76

Nisoldipine coat-core is a long-acting formulation of the dihydropyridine calcium antagonist (calcium channel blocker) nisoldipine, suitable for once daily administration in the treatment of patients with hypertension. In clinical trials in patients with mild to moderate hypertension, nisoldipine coat-core has efficacy and tolerability similar to those of other calcium antagonists, and antihypertensive efficacy equivalent to that of agents from various other drug classes including beta-blockers, thiazide diuretics and ACE inhibitors. Unlike beta-blockers and thiazide diuretics, calcium antagonists (including nisoldipine coat-core) are not associated with clinically significant adverse metabolic effects on the serum lipid profile or glycaemic control. Nevertheless, published guidelines or consensus papers on the pharmacological management of patients with hypertension recommend calcium antagonists (and other drugs) as "alternative first-line' agents, while beta-blockers and diuretics are generally considered to be first-line therapy because of demonstrated benefits in terms of cardiovascular morbidity and mortality in this clinical setting. Nisoldipine coat-core maintains consistent plasma drug concentrations and antihypertensive effects throughout the 24-hour dosage interval, thereby attenuating intermittent reflex increases in sympathetic activity. This pharmacological profile may have important clinical implications; recent retrospective data suggest an association between moderate to high dosages of short-acting dihydropyridine calcium antagonists and adverse cardiovascular events, although this has yet to be confirmed in large prospective trials. In addition, the high degree of vasoselectivity of nisoldipine minimises negative inotropic effects which may be observed with less selective agents such as nifedipine. Nisoldipine coat-core is, therefore, a useful alternative to other antihypertensive agents in the management of patients with hypertension, providing consistent antihypertensive efficacy and good tolerability with once daily administration.
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PMID:Nisoldipine coat-core. A review of its pharmacology and therapeutic efficacy in hypertension. 884 41

Twenty-four patients completed a dose ranging study of the effect of nisoldipine as monotherapy in the treatment of hypertension. This randomized double-blind study consisted of two crossover phases in each of which once and twice daily treatment were compared. In the first treatment phase the total daily dose of nisoldipine was 10 mg, which increased to 20 mg during the second phase. Trough blood pressure measurements were made 12/24 h postdose. During the first phase the blood pressure values following treatment with nisoldipine 5 mg twice daily were significantly lower than with 10 mg once daily. However, when the daily dose was increased to 20 mg there was no significant difference between the two treatment regimens. There was also no significant difference between nisoldipine 5 mg twice daily and 10 mg twice daily but the results for 20 mg once daily were significantly lower than for 10 mg once daily. Four patients withdrew from the study because of adverse events, one while on placebo and three while on nisoldipine therapy. Between 33 percent and 47 percent of patients reported adverse events during nisoldipine treatment but the majority of adverse events reported were mild and did not require treatment withdrawal. Nisoldipine twice daily appeared to be more effective and better tolerated than once daily treatment for 24-h blood pressure control.
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PMID:Comparison of once daily and twice daily nisoldipine as monotherapy in essential hypertension. 886 64

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
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PMID:What, if anything, is controversial about calcium antagonists? 896 30

Nisoldipine coat core (CC) is a long-acting calcium channel blocker (CCB) with a slow and smooth onset of action. It is effective in the treatment of angina pectoris, increasing exercise duration, time to ST segment depression and time to onset of angina. The results of two studies reviewed here, in which patients received concomitant treatment with a beta-blocker, showed that the anti-anginal efficacy of nisoldipine CC, 40 mg once daily, measured at trough was comparable with amlodipine, 10 mg once daily, and with diltiazem retard, 120 mg twice daily, and that efficacy was maintained over a 24-hour period. The third trial reviewed here showed that nisoldipine CC was at least as effective as three-times-daily treatment with diltiazem (total dose 240 mg). To date, the effects of nisoldipine CC have been investigated in over 4,000 patients with hypertension and angina pectoris. Clinical experience suggests that once-daily nisoldipine CC is at least as well tolerated as other CCBs, provides consistent efficacy and is a useful treatment in the management of patients with angina pectoris. The CCBs show promising beneficial effects in experimental atherosclerosis and a small number of clinical trials show some effect on the progression of atherosclerosis in coronary artery disease and restenosis following coronary angioplasty. An ongoing long-term trial with nisoldipine CC after coronary angioplasty is discussed.
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PMID:Nisoldipine CC: clinical experience in ischaemic heart disease. 911 64

Nisoldipine coat core (CC) is a long-acting formulation of the dihydropyridine calcium channel blocker nisoldipine, suitable for once-daily administration in the treatment of patients with hypertension. Data are reported from three randomized, controlled trials. In two of these, nisoldipine CC was shown to be equivalent in efficacy and tolerability to atenolol in patients with mild to moderate hypertension and to enalapril in elderly patients with hypertension. In a third study using ambulatory blood pressure monitoring in black patients with severe hypertension, nisoldipine CC maintained blood pressure control over the 24-hour dosing period. In addition, regression of left ventricular (LV) mass and improvement in LV function were observed at the end of the 4-month treatment period. Further data are presented from a pharmacokinetic pharmacodynamic modelling study investigating the potential effects of dose-dumping of nisoldipine from the controlled-release formulation, which may occur when the drug is taken with food. This study illustrates the superior control of plasma nisoldipine concentrations and blood pressure provided by the CC compared with an immediate-release formulation, and indicates that an interaction between nisoldipine CC and food is unlikely to cause adverse events. The results of these trials provide further support for the use of nisoldipine CC as an effective agent for the treatment of patients with hypertension, providing consistent antihypertensive efficacy and good tolerability with once-daily administration.
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PMID:Nisoldipine CC: clinical experience in hypertension. 911 69

Nisoldipine is a second-generation dihydropyridine calcium channel blocker (CCB). It is the most vascular selective of the currently available CCBs, and thus has the capacity to lower blood pressure without affecting the functioning of the myocardium and skeletal muscle, and without producing any negative inotropic effects. Nisoldipine coat core (CC) is an extended-release formulation that allows nisoldipine to be released gradually over 24 hours, minimizing fluctuations in plasma concentration and providing a good trough/peak ratio. It has a slow onset and long duration of action, and ambulatory blood pressure monitoring has demonstrated that its antihypertensive effect is maintained over 24 hours with no evidence of reflex tachycardia, hypotension, or sympathetic neurohormonal activation and no effects on circadian variation. Studies in patients with hypertension have shown that nisoldipine CC provides reductions in blood pressure that are at least equivalent to those seen with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and other CCBs, without deleterious effects on metabolic parameters. In particular, it has been found to be effective in elderly patients and in black patients with severe hypertension. The DEFIANT studies have demonstrated that nisoldipine CC improves cardiac function and exercise tolerance in patients recovering from acute myocardial infarction, without increasing the risk of mortality compared with placebo. It also improves exercise performance in patients with stable angina pectoris. Nisoldipine CC is well tolerated in all groups of patients, with the most frequently reported side effects being headache and peripheral edema, which are usually mild and transient.
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PMID:Nisoldipine CC: efficacy and tolerability in hypertension and ischemic heart disease. 912 76


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