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Query: UMLS:C0085580 (essential hypertension)
 14,686 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

The mechanism by which hypertension produces renal damage remains poorly defined. Experimental evidence suggests that glomerular hypertension/hyperfiltration constitutes a potential mechanism by which hypertension leads to chronic renal failure. Renal functional reserve has been used to investigate the presence or absence of hyperfiltration, both in experimental animals and humans. Micropuncture studies using the two-kidney, one-clip hypertension model have shown that glomerular hypertension/hyperfiltration is associated with loss of renal functional reserve. However, loss of renal functional reserve in this experimental model is not always indicative of hyperfiltration because some antihypertensive agents (Verapamil, Losartan) correct glomerular hypertension/hyperfiltration, but do not restore renal reserve. Renal reserve has also been evaluated in patients with essential hypertension. Some investigators have shown that hypertension is associated with loss of renal functional reserve which can be restored in some studies with antihypertensive therapy. However, normal renal reserve has also been shown in hypertensive patients. Altogether, these data suggest that renal functional reserve cannot be used to assess the role of hemodynamic mechanisms in hypertension-induced renal injury. Long-term follow-up studies are required to establish if loss of renal reserve is indicative of risk factors leading to renal failure in patients with systemic hypertension.
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PMID:Renal reserve in patients with high blood pressure. 852 52

The VHAS (Verapamil-Hypertension Atherosclerosis Study) Investigators entered 1464 patients with essential hypertension and blood pressure (BP) values > or = 160 mmHg systolic and 95 mmHg diastolic (DBP) but excluded those with a DBP > or = 115 mmHg, and those with diabetes mellitus or previous myocardial infarction or cerebrovascular episodes. Patients were randomly allocated to drug therapy for 2 years with either slow-release verapamil 240 mg once daily or chlorthalidone 25 mg once daily, with nonresponders receiving additional captopril 25 mg daily. A random group of eligible patients (n = 494) was followed for a more extended period (4 years) using beta-mode ultrasound. The end point is the development of atherosclerosis detected by ultrasound imaging. The most interesting observation thus far is that in this population of middle-aged hypertensives without a history of previous cardiovascular events, about two thirds had asymptomatic carotid alterations. The study is ongoing.
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PMID:Vascular complications in hypertension: the VHAS study. Verapamil-Hypertension Atherosclerosis Study. 856 70

The wide use of ABPM has resulted in greater appreciation of the circadian time structure of BP variability and its clinical relevance. It is now recognized that the day-night change in BP results from an interplay of circadian rhythms in neurohumoral mechanisms coupled with temporal patterns in physical activity and mental load. The composite effect and balance of these endogenous and exogenous cyclic phenomena give rise to elevated BP during diurnal activity and reduced BP during nighttime repose in both normotension and uncomplicated essential hypertension. The balance is frequently disturbed in complicated and secondary forms of hypertension causing gross alteration of the 24-hour BP profile. ABPM also reveals the efficiency of antihypertensive treatment throughout the 24 hours and as a function of drug administration time. The pharmacokinetics and/or pharmacodynamics of antihypertensive medications have been demonstrated to vary with ingestion time. Such time-dependencies arise from circadian rhythms in BP and underlying mechanisms. The effect of antihypertensive medications is not simply superimposed upon endogenous bioperiodicities. Rhythms in neurohumoral mechanisms of BP control may modulate treatment effect. Certain aspects of the shape of the 24-hour BP profile, such as the magnitude of the morning surge and nocturnal decrease, have been implicated as determinants of morbid and mortal cardiovascular events. One large clinical multicenter investigation, known as the CONVINCE (Controlled Onset Verapamil Investigation of Clinical Endpoints) trial, is aimed at assessing the impact (cardiovascular morbidity and mortality) of verapamil chronotherapy over standard diuretic or beta anatagonist treatment in hypertensive patients with at least one risk factor of coronary heart disease. ABPM will help ascertain to what extent depression of the morning surge in BP relates to reduction in cardiac morbidity and mortality in this as well as other such trials. In any event, the importance of ABPM and the indices derived from its application are just beginning to be appreciated and explored.
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PMID:Ambulatory blood pressure monitoring. Application to clinical medicine and antihypertension medication trials. 885 50

Verapamil sustained-release (SR)/trandolapril is a combination of a phenylalkylamine calcium antagonist and an angiotensin converting enzyme inhibitor for the management of essential hypertension. Verapamil SR/trandolapril does not adversely influence glucose, insulin or lipid parameters in patients with mild to moderate essential hypertension and type 2 (non-insulin-dependent) diabetes mellitus with or without elevated cholesterol and/or triglyceride levels. Verapamil SR/trandolapril reduces proteinuria to a greater extent than the individual components in patients with diabetic or non-diabetic proteinuria. The antihypertensive efficacy of once daily verapamil SR/trandolapril (180/1 or 180/2 mg) for 8 weeks or 6 months is similar to that of atenolol/chlorthalidone (100/25 mg) and lisinopril/hydrochlorothiazide (20/12.5 mg), and was at least as good as that of metoprolol/hydrochlorothiazide (100/12.5 mg) in a small trial. The reduction in sitting or supine diastolic and systolic blood pressure is greater after verapamil SR/trandolapril (180/2 to 240/4 mg) than after monotherapy with verapamil SR (180 and 240 mg/day) or trandolapril (2 to 8 mg/day). Fewer cardiac events occurred after verapamil SR/trandolapril (240/1 to 360/2 mg/day) than after trandolapril (1 to 2 mg/day) in postmyocardial infarction patients with congestive heart failure. The incidence of adverse events after verapamil SR/trandolapril is similar to that of comparator drugs and the individual components of the combination.
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PMID:Fixed combination verapamil SR/trandolapril. 982 57

A novel verapamil chronotherapeutic oral drug absorption system (CODAS-Verapamil) designed for bedtime dosing and with controlled onset and extended-release properties was evaluated in 257 patients with mild-to-moderate essential hypertension in an 8-week, double-blind, placebo-controlled trial. After bedtime dosing (9 PM to 11 PM, this delivery system delays drug release for 4 to 5 h, and provides the highest concentrations of verapamil between 6 AM and noon. The study results showed that CODAS-verapamil produced its greatest antihypertensive effect during this morning period (6 AM to 12 noon) and also provided effective trough diastolic blood pressure reductions at 200, 300, and 400 mg. Significant trough systolic blood pressure reductions were achieved only with the 300- and 400-mg doses. The nighttime dosing regimen was not associated with excessive blood pressure (BP) reductions during the sleeping hours, when the antihypertensive effect was generally slightly less than that of the 24-h mean reduction. The CODAS-verapamil provides enhanced BP reduction during the morning period when compared with other time intervals of the 24-h dosing period.
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PMID:A new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning. 1120 72

Fixed verapamil SR/trandolapril combinations 180/1 mg and 180/2 mg (Tarka, Knoll AG) have a significantly superior antihypertensive effect compared to equal dosages of either agent alone. Verapamil SR/trandolapril 180/2 mg combination produces the best dose-response ratio of different dose combinations of these two drugs. Combination therapy has the most pronounced effect on blunting the early morning rise in blood pressure. Thus, verapamil SR/trandolapril combination therapy may be an appropriate treatment option in patients with moderate essential hypertension, particularly in those who have a tendency toward the early morning rise in blood pressure. The adverse effect profile of the fixed combination of verapamil SR/trandolapril includes the typical side effects of its monocompounds. The fixed combination of verapamil SR/trandolapril is also effective and safe in the treatment of hypertension in the elderly. The fixed low-dose combination therapy with verapamil SR/trandolapril 180/2 mg is a suitable treatment option for patients with moderate essential hypertension and Type 2 diabetes mellitus, because it improves parameters of carbohydrate metabolism and uricaemia and does not alter the lipid profile. The insulin-sensitising effect of angiotensin converting enzyme (ACE) inhibitor monotherapy with its theoretical risk of hypoglycaemia is completely neutralised in the combination with verapamil SR. Comparative studies have shown that the low-dose combination of verapamil SR/trandolapril may be a suitable alternative to combinations containing a thiazide diuretic or a beta-blocking agent for the long-term management of hypertensive patients for whom combination therapy is indicated. The combination of an ACE inhibitor with a non-dihydropyridine calcium channel blocker reduces proteinuria to a greater extent than either agent alone. A combination of an ACE inhibitor and a calcium channel blocker may provide additional benefit in inducing the regression of left ventricular hypertrophy. Combination therapy leads to a significant increase in left ventricular ejection fraction, improvement of wall motion index and increases exercise duration time in patients with coronary heart disease and left heart failure. It also improves the ratio of exercise to rest rate-pressure product and decreases the number of angina attacks. These findings support the hypothesis that the combination of verapamil and trandolapril might be useful in patients with attenuated left ventricular function and angina pectoris. Thus, Tarka is an effective and well-tolerated antihypertensive agent with a good safety profile and positive metabolic effects.
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PMID:The fixed combination of verapamil SR/trandolapril. 1124 35

BACKGROUND: In general clinical practice, physicians prescribe calcium channel blockers to a wide range of patients with differing demographic characteristics and hypertension history. This study was undertaken to investigate the effectiveness and safety of sustained-release verapamil (Verelan((R)), verapamil HCl) in patients with essential hypertension, studied under "usual use" conditions. METHODS: In this prospective, open-label, postmarketing surveillance study, 25 089 patients with hypertension received once-daily verapamil therapy for 4 weeks, during which they were evaluated by 8106 physicians at baseline and at two follow-up visits (weeks 2 and 4). In this study, hypertension was defined as an average sitting diastolic blood pressure (DBP) of greater-than-or-equal 90 mm Hg at baseline. Previously diagnosed hypertensive patients with a sitting DBP <90 mm Hg but experiencing untoward effects requiring discontinuation of current antihypertensive therapy were also included. RESULTS: Eighty-five percent (n = 21 446) of the total patients enrolled at baseline completed this office-based trial. Nearly 24% of patients were newly diagnosed hypertensives. At baseline, the mean systolic blood pressure (SBP) and diastolic blood pressure were 161 and 96 mm Hg, respectively. In evaluable patients with mild, moderate, and severe hypertension, as stratified by baseline measurements, treatment with verapamil produced DBP reductions of 12, 19, and 29 mm Hg, respectively. Verapamil treatment produced clinically similar SBP, DBP, and HR (heart rate) reductions across gender and racial groups studied (white, black, Hispanic, and Asian). Only 6.1% of patients failed to complete the study because of any reported adverse experiences (4.5% of patients discontinued because of adverse experiences considered drug related). Constipation (5.0%) and headache (1.1%) were the most commonly reported adverse events. CONCLUSION: In general clinical practice, verapamil is well tolerated and effective in a broad range of hypertensive patients.
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PMID:Large-Scale Postmarketing Surveillance of Hypertensive Patients Treated with Verapamil. 1185 Jun 91

An open-label, multicenter, dose-titration study evaluated 2,556 patients with stage I or II essential hypertension (untreated or previously treated with one antihypertensive agent) to assess the effect of a chronotherapeutic formulation of verapamil (Verelan PM) designed to provide maximum plasma concentrations in the midmorning hours. After starting with 200 mg/d at bedtime, the dose of Verelan PM was titrated to a maximum of 400 mg/d at 4-week intervals to achieve a target blood pressure (BP) <140/90 mm Hg using morning BP measurements. In 85.3% of patients, a diastolic blood pressure (DBP) response to less than 90 mm Hg or a 10-mm Hg decline from baseline DBP was achieved. The systolic BP response (<140 mm Hg or 10% decline from baseline) was attained in 76.9% of patients. Blood pressure was controlled in 62.6% of patients with Verelan PM monotherapy. Upward titration of Verelan PM from 200 to 400 mg nearly doubled the DBP response rate (45.8% to 85.3%). This chronotherapeutic formulation of verapamil was well tolerated in this community trial.
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PMID:Chrono: a community-based hypertension trial of a chronotherapeutic formulation of verapamil. 1242 3

Trandolapril/verapamil sustained release (SR) [Tarka] is an oral, fixed-dose combination of the ACE inhibitor trandolapril and the SR formulation of the phenylalkylamine calcium channel antagonist verapamil. It is indicated for the treatment of hypertension in patients who require more than one agent to achieve blood pressure (BP) targets. In the large, randomised, multicentre INVEST (INternational VErapamil SR/trandolapril STudy), a verapamil SR-based treatment strategy that included trandolapril in most patients was as effective as an atenolol-based treatment strategy in reducing the risk of the primary outcome (first occurrence of death [all-cause], nonfatal myocardial infarction [MI] or nonfatal stroke) in patients with hypertension and coronary artery disease (CAD) and was as well tolerated. Trandolapril/verapamil SR is generally more effective at controlling hypertension than either component as monotherapy, and is as effective as a number of other fixed-dose combination therapies. The combination is as well tolerated as trandolapril monotherapy and is at least as well tolerated as verapamil SR monotherapy. In hypertensive patients with type 2 diabetes mellitus in the BENEDICT (BErgamo NEphrologic DIabetes Complications Trial), trandolapril/verapamil SR prolonged the time to the onset of persistent microalbuminuria compared with placebo, as did trandolapril monotherapy. Thus, trandolapril/verapamil SR is an effective option for the treatment of essential hypertension in patients requiring more than one agent to achieve BP targets, including those with compelling indications, such as CAD or type 2 diabetes.
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PMID:Trandolapril/verapamil sustained release: a review of its use in the treatment of essential hypertension. 1611 84


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