Antihypertensive effects of nitrendipine and cilazapril alone, and in combination in hypertensive patients with chronic renal failure.

Kloke, H. J.; Huysmans, F. T. M.; Jf, Wetzels; Sluiter, H E; Kleinbloesem, C. H.; Koene, R. A. P.

doi:10.1111/j.1365-2125.1989.tb03494.x

Cited by 16 publications

(2 citation statements)

References 44 publications

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“…The combination of a calcium antagonist and an ACE inhibitor may be useful in the treatment of hypertension, since in some studies an ACE inhibitor plus a calcium antagonist reduced blood pressure more than either drug alone (Brouwer et al 1985;Gennari et al 1989;quazzi et al 1984;Kloke et al 1989;Singer et al 1987). There are some reports describing that coadministration of a calcium antagonist with an ACE inhibitor has additive pharmacodynamic effects without pharmacokinetic interactions.…”

Section: Calcium Channel Antagonistsmentioning

confidence: 95%

Pharmacokinetic Drug Interactions with ACE Inhibitors

Shionoiri

1993

Clinical Pharmacokinetics

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Angiotensin converting enzyme (ACE) inhibitors which have active moieties excreted mainly in urine require adjustment of either the dose or the interval between doses in patients with moderate to severe renal dysfunction or severe congestive heart failure. Those agents such as temocapril (CS 622) and fosinopril, excreted both in urine and bile, may not require such adjustment. Renal clearance of ACE inhibitors may be reduced and some accumulation may occur in elderly patients with mild renal dysfunction or congestive heart failure. The bioavailability of ACE inhibitors is reduced by concomitant food or antacids which may slow gastric emptying and raise gastric pH. Pharmacokinetic interactions with ACE inhibitors are unlikely in patients receiving thiazide or loop diuretics. When ACE inhibitors are given hyperkalaemia may occur in patients with renal insufficiency, those taking potassium supplements or potassium-sparing diuretics, and in diabetic patients with mild renal impairment. While no pharmacokinetic interaction precludes use of this combination, the pharmacokinetics of some ACE inhibitors are subject to greater variability when patients also receive beta-blockers. Calcium antagonists and ACE inhibitors have additive anti-hypertensive effects and pharmacokinetic interactions between these agents are unlikely. One report exists of a significant effect of coadministered hydralazine on the pharmacokinetics and urinary excretion of lisinopril. Data on interactions between ACE inhibitors and digitalis are contradictory. There is no evidence that the concomitant use of ACE inhibitors and digoxin is associated with an increased risk of digitalis toxicity. ACE inhibitors are mainly excreted by glomerular filtration and renal tubular secretion. Possible interactions between ACE inhibitors and probenecid have been noted, with renal and total body clearance of ACE inhibitors being potentially reduced in the presence of probenecid. Probenecid pretreatment may enhance the pharmacodynamic response of ACE inhibitors. Few but contradictory data exist on the effects of H2-blockers on ACE inhibitor pharmacokinetics and little information is available on interactions between ACE inhibitors and hypoglycaemic drugs. Some case reports link ACE inhibitors with the induction of lithium toxicity. Coadministration of lithium should be undertaken with caution, and frequent monitoring of lithium concentrations is recommended with all ACE inhibitors. Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the haemodynamic actions of ACE inhibitors. NSAIDs reduce renal excretion of ACE inhibitors, with a corresponding increase in circulating drug concentrations. There is little information available on the pharmacokinetic interaction with ACE inhibitors and cyclosporin, but caution should be employed when they are used together.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Calcium Channel Antagonistsmentioning

confidence: 95%

Pharmacokinetic Drug Interactions with ACE Inhibitors

Shionoiri

1993

Clinical Pharmacokinetics

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“…[8][9][10] Furthermore, it has been found that when the two drug classes are given in combination they have an additive effect. [11][12][13][14][15] Randomised clinical controlled studies have shown that the combination of the two drug classes is associated with significant antihypertensive effect and is well-tolerated. [16][17][18][19] The combination of these two classes is rational, since they have complementary mechanisms of action.…”

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confidence: 99%

Long-Term Tolerability and Efficacy of the Fixed Combination of Manidipine and Delapril in Patients with Essential Hypertension

Kárpáti¹,

Alberici

Musumeci³

et al. 2003

High Blood Pressure & Cardiovascular Prevention

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Aim:The aim of this study was to assess the long-term tolerability and efficacy of a fixed combination of manidipine 10mg and delapril 30mg (M+D) as an antihypertensive treatment in patients with mild to moderate hypertension. Study design: This was a multicentre open study, with a two-week placebo run-in period, followed by a 50-week active treatment period. Three hundred and nine patients with a mean age of 56.4 years and a sitting (Si) diastolic blood pressure (DBP) of ≥95mm Hg and ≤110mm Hg were enrolled. During the treatment period systolic blood pressure (SBP) and DBP were assessed by conventional sphygmomanometry. Results: The decreases in SiSBP and SiDBP were clinically relevant after 4 weeks of treatment, with a mean reduction of 16.6mm Hg (95% confidence interval [CI] -18.2; -15) and 9.3mm Hg (95% CI -10.2; -8.4), respectively. At the end of treatment, SiSBP and SiDBP were significantly decreased by 21.8mm Hg [95% CI -23.4; -20.2) and 14.3mm Hg (95% CI -15.3; -13.4), respectively. Pulse pressure (PP) was 61.4 ± 9.8mm Hg at baseline and was reduced to 54.2 ± 10.8mm Hg after the first month of treatment (-7.3mm Hg, 95% CI -8.5; -6); at 50 weeks of treatment the PP was 54 ± 11mm Hg (-7.5mm Hg, 95% CI -8.8; -6.1). The success rate (reduction of SiDBP ≥10mm Hg from baseline or SiDBP ≤90mm Hg) was 86.4%, the normalisation rate (SiDBP ≤90mm Hg) was 80.6%. Forty-four patients (14.2%) reported adverse drug-related events. No clinically significant changes in heart rate, ECG or laboratory tests were found. Conclusion: The fixed combination M+D is effective in reducing blood pressure levels in patients with hypertension and in maintaining the reduction throughout the study period, with a good tolerability profile.

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Newer Approaches to Antihypertensive Therapy

Epstein¹

1996

Arch Intern Med

111

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Despite the availability of many newer antihypertensive agents, hypertensive patients remain at higher risk of premature death than the general population. This persistence of morbidity and mortality may be accounted for by the frequent failure to achieve adequate blood pressure reduction despite an extensive array of available antihypertensive agents. Such considerations have led to reassessment of the potential role of fixed-dose combination agents in the antihypertensive armamentarium. The rationale for combination therapy relates to the concept that antihypertensive efficacy may be enhanced when 2 classes of agents are combined. In addition, combination therapy enhances tolerability-1 drug of a fixed combination can antagonize some of the adverse effects of the second drug. Fixed-dose combination therapy simplifies the treatment regimen, preventing treatment failures that might result from missed doses. An additional novel concept is the possibility of enhancing salutary effects on target organs, including regressing left ventricular hypertension and retarding progression of renal disease, by combination therapy over and above the effects expected from the fall in arterial pressure alone. The recent approval by the Food and Drug Administration of 2 fixed-dose angiotensin-converting enzyme inhibitor/calcium antagonist combinations has focused attention on and prompted reexamination of this issue.

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Antihypertensive effects of nitrendipine and cilazapril alone, and in combination in hypertensive patients with chronic renal failure.

Cited by 16 publications

References 44 publications

Pharmacokinetic Drug Interactions with ACE Inhibitors

Pharmacokinetic Drug Interactions with ACE Inhibitors

Long-Term Tolerability and Efficacy of the Fixed Combination of Manidipine and Delapril in Patients with Essential Hypertension

Newer Approaches to Antihypertensive Therapy

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