Factors influencing the hypotensive effects of calcium antagonists.

Erné, Paul; Bolli, Peter; Bertel, Osmund; Hulthén, U L; Kiowski, Wolfgang; Müller, Franco B.; Bühler, Fritz R.

doi:10.1161/01.hyp.5.4_pt_2.ii97

Cited by 126 publications

(38 citation statements)

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“…Other studies have demonstrated (Weber & Drayer, 1984;Ruddel et al, 1984;Buhler et al, 1982) that the antihypertensive efficacy varies from patient to patient. In contrast to other studies (Muller et al, 1984;MacGregor et al, 1982;Erne et al, 1983), we found no statistically significant correlation between pretreatment blood pressure level and the degree of blood pressure response. The short half-life of nitrendipine (Aronoff & Sloan, 1985;Goa & Sorkin, 1987) and the low dosage used may explain the reduced antihypertensive efficacy at 3 h compared with that at 1 h after drug administration.…”

Section: Discussioncontrasting

confidence: 99%

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

Kloke¹,

Huysmans²,

Jf³

et al. 1989

Brit J Clinical Pharma

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1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double‐blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/‐ 3/96 +/‐ 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/‐ 1.8% and 8.0 +/‐ 1.9%, and after 1 week of treatment 5.0 +/‐ 2.4% and 8.1 +/‐ 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussioncontrasting

confidence: 99%

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

Kloke¹,

Huysmans²,

Jf³

et al. 1989

Brit J Clinical Pharma

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“…15 Conversely, dietary salt loading in two hypertensive rat strains dramatically increased dihydropyridine receptors. 16 Furthermore, the clinical antihypertensive effect of another type of calcium channel blocking drug, verapamil, is also enhanced in low renin hypertensive individuals, 4 and the longer-term antihypertensive efficacy of nifedipine may also be predicted by initial serum ionized calcium levels. 17 Finally, the present study suggests the importance of in vivo calcium transport in mediating the tightly coupled renin-induced stimulation of adrenal aldosterone secretion.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, calcium channel blocking agents were found to lower pressure preferentially in lower renin forms of experimental as well as human hypertension. 3 - 4 We would similarly predict that differing initial levels of extracellular calcium would also affect the hypotensive efficacy of calcium blocking drugs. However, no studies to date have related clinical indices of calcium metabolism to the effects of these agents.…”

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confidence: 99%

Calcium, the renin-aldosterone system, and the hypotensive response to nifedipine.

Resnick¹,

Nicholson²,

Laragh³

1987

Hypertension

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SUMMARY Ionic, hormonal, and blood pressure responses to a single oral dose of the calcium channel blocker nifedipine were assessed in 25 essential hypertensive subjects. When grouped according to their renin-sodium profile, low renin subjects had a greater hypotensive response to nifedipine (change in diastolic blood pressure -20.0± 1.4 vs -6.4 ± 1.0%; p<0.005) than did high renin hypertensive subjects. The initial level of serum ionized calcium predicted the blood pressure response to nifedipine (r = 0.70, p<0.001), as did the initial plasma renin activity (r=0.65, p<0.005). Nifedipine induced a transient rise in serum ionized calcium (from 2.22 ± 0.02 to 2.28 ± 0.02 mEq/L; p<0.01), while plasma renin activity was consistently elevated compared with initial values at 30 (p<0.01), 60 (p<0.01), and 120 (p<0.05) minutes after drug administration. By comparison, plasma aldosterone levels did not rise and even declined at 30 (p<0.01), 60 (p<0.05), and 120 (p < 0.05) minutes after nifedipine. These results suggest that low renin hypertension is more critically dependent on extracellular calcium than are higher renin forms and demonstrate that levels of serum ionized calcium, plasma renin activity, or both may predict the sensitivity of blood pressure to calcium channel blockade. Lastly, calcium may play a pivotal role in vivo in coupling renin stimulation to adrenal aldosterone responses. (Hypertension 10: 254-258, 1987) KEY WORDS hypertension calcium metabolism * renin activity • calcium channel blockade V ARIOUS abnormalities of calcium metabolism have recently been described in both experimental and human forms of hypertension, 1 although the specific manner in which these abnormalities relate to the elevations in pressure remains unknown. We have recently demonstrated consistent relationships between circulating levels of ionized calcium and the concurrent plasma renin activity in human essential hypertension.2 Low renin essential hypertensive subjects had lower average levels of serum ionized calcium compared with both other hypertensive subjects and normotensive control subjects. We hypothesized that lower serum levels of ionized calcium in these subjects reflected an increase in intra- cellular calcium levels, and thus an altered steady state distribution of calcium between intracellular and extracellular compartments. If this hypothesis is correct, one might expect an enhanced dependence of blood pressure on the extracellular calcium pool in the low renin hypertensive state. Therefore, blood pressure in these subjects ought to be more sensitive to blockade of intracellular calcium accumulation from extracellular sites. Indeed, calcium channel blocking agents were found to lower pressure preferentially in lower renin forms of experimental as well as human hypertension. 3 - 4 We would similarly predict that differing initial levels of extracellular calcium would also affect the hypotensive efficacy of calcium blocking drugs. However, no studies to date have related clinical indices of calcium metabolism to ...

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“…Efficacy and tolerability of nicardipine 141S apy for the treatment of essential hypertension (Gould et al, 1983;Erne et al, 1983). They have been reported to be well tolerated and to lack many of the side-effects of other popular anti-hypertensive drugs, such as the biochemical disorders associated with thiazide diuretics (Amery et al, 1978;Grimm et al, 1981) or the side effects of lethargy, cold extremities, and bronchospasm following,B-adrenoceptor antagonists (Besterman, 1983).…”

Section: Discussionmentioning

confidence: 99%

A study of the long‐term efficacy and tolerability of oral nicardipine in hypertensive patients.

Taylor¹,

Frais²,

Lee³

et al. 1985

Brit J Clinical Pharma

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1 This study was designed to evaluate the efficacy of oral nicardipine in 91 patients with uncomplicated essential hypertension over a period of 12 months. All patients started on a fixed nicardipine dose of 30 mg three times daily which was adjusted in the range 10-40 mg three times daily, where necessary to achieve a target diastolic blood pressure < 95 mm Hg. 2 At 6 weeks, blood pressure (mean + s.e. mean) was reduced from an average of 190+22/112+8 to 167+23/96+llmmHg supine and from 180+21/113+7 to 154+ 17/95+11 mm Hg standing and remained controlled in all patients throughout the study.3 A total of96 unwanted experiences were reported by 49 patients (54 % ); 17 (19 % ) reported a single symptom once and two (2% ) reported a single symptom more than once. The most frequently reported adverse experiences were peripheral oedema in 27 (28% ) and headaches in 15 patients (16%). 4 The majority of the adverse experiences occurred in the first 3 months of treatment. Ten patients (11 % ) withdrew from the study during this time and eight (9 % ) in the subsequent 9 months because of drug-related side effects; five others (5%) withdrew for unrelated reasons. 5 The incidence of adverse experiences was dose-related. Three patients reported unwanted effects on 10 mg three times daily, eight on 20 mg three times daily, 36 on 30 mg three times daily, and 12 on 40 mg three times daily oral nicardipine. 6 The relatively high incidence ofreported adverse experiences may reflect the fact that there was no comparative placebo control group and that patients were encouraged to report all adverse experiences.

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Factors influencing the hypotensive effects of calcium antagonists.

Cited by 126 publications

References 0 publications

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

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

Calcium, the renin-aldosterone system, and the hypotensive response to nifedipine.

A study of the long‐term efficacy and tolerability of oral nicardipine in hypertensive patients.

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