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At least 199 records · Page 11Linked to original sources
PubMed1993

Erythrocyte sodium cannot predict hypotensive effects of calcium channel blockers.

Antihypertensive efficacy of the calcium channel blocker, nilvadipine, was investigated in 21 patients with essential hypertension in relation to the intracellular sodium concentration ([Na]i) in erythrocytes and clinical variables, such as age, body weight, pretreatment blood pressure and plasma renin activity. Dihydropyridine nilvadipine reduced mean blood pressure from 120 +/- 6 to 106 +/- 8 mmHg (p < 0.01). The hypotensive effect of nilvadipine was positively correlated with age (r = 0.67, p < 0.01) and inversely correlated with plasma renin activity (r = -0.62, p < 0.01), but was not correlated with erythrocyte [Na]i or any other indices. Erythrocyte [Na]i was decreased with nilvadipine treatment (8.27 +/- 1.69 to 7.97 +/- 1.49 mM, p < 0.01). However, no link was found between the change in [Na]i and the hypotensive effect of the drug. In conclusion, the antihypertensive efficacy of nilvadipine was predictable by age and renin status, but not by erythrocyte [Na]i. A significant role of reduction of [Na]i in the hypotensive effect of the calcium channel blockers was not detected.

Age Factors↗
PubMedDate not supplied

Inhibition of tumor cell-platelet interactions and tumor metastasis by the calcium channel blocker, nimodipine.

Nimodipine, a dihydropyridine calcium channel blocker, was evaluated in vitro for its ability to inhibit platelet aggregation induced by B16 amelanotic melanoma (B16a) and Walker 256 carcinosarcoma (W256) cells, and for its ability to inhibit platelet-enhanced B16a and W256 adhesion to rat microvascular endothelial cells. Nimodipine produced a dose-dependent inhibition of tumor-cell-induced platelet aggregation (TCIPA). Platelets enhanced tumor cell adhesion to endothelium both in the presence and absence of overt platelet aggregation. However, the greatest enhancement of adhesion occurred under aggregatory conditions. Nimodipine at a dose of 40 micrograms/ml inhibited platelet-enhanced adhesion to endothelium under aggregatory and nonaggregatory conditions. Nimodipine was tested in vivo for its ability to inhibit both "experimental' and spontaneous metastasis. Nimodipine produced a 46 per cent inhibition of lung colony formation at a dose of 5 mg/kg body-weight. Over a dose range of 0.1-80 mg/kg, nimodipine produced a significant dose-dependent inhibition in the formation of lung metastases from a subcutaneous tumor. The in vitro results demonstrate that a dihydropyridine calcium channel blocker can inhibit tumor cell-platelet-endothelial cell interactions. The in vivo results suggest that these compounds may be a new class of antimetastatic agent.

Animals↗
PubMed2006

Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker.

Benidipine is a dihydropyridine-derived calcium channel blocker developed in Japan, with several unique mechanisms of action, that is, triple calcium channels (L, N, and T) blocking action with a membrane approach. Benidipine has relatively high vascular selectivity and is expected to show protective effects on vascular endothelial cells. Renal protective effects of benidipine also have been shown in several basic and clinical studies. Moreover, anti-oxidative action and enhancing nitric oxide production have been noted with this drug, following its cardio-protective effects in patients with ischemic heart diseases. In fact, benidipine exerted a better prognostic effect than other calcium channel blockers in the therapy for patients with vasospastic angina. In addition, benidipine showed reliable antihypertensive, renoprotective effects if used in combination with angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive effects are not achieved by ARBs alone, indicating that benidipine is an useful calcium channel blocker in combination therapy for hypertension. Benidipine was launched on the Japanese market 14 years ago, but few severe side effects have been reported, suggesting that this is a drug with established safety and long-acting pharmacological effects.

Angina Pectoris↗
PubMed1993

New uses for calcium channel blockers. Therapeutic implications.

Calcium antagonists block calcium entry into cells, resulting in relaxation of smooth muscle and limitation of the cytotoxic effects of ischaemia in various organ systems. They are most frequently used for clinical conditions requiring vasodilatation, i.e. hypertension and Raynaud's phenomenon, and this also suggests that the most common adverse effect of these drugs for noncardiovascular indications is an unwanted decline in blood pressure. Other uses include treatment of supraventricular arrhythmias and angina. There is some evidence that these drugs retard the development of atherosclerosis. Calcium channel blockers also improve renal reperfusion and may reduce renal insufficiency due to various nephrotoxins, and are particularly useful in renal transplantation for protection against cyclosporin toxicity and post-transplant acute tubular necrosis. These drugs are also useful in pregnancy-induced hypertension and unwanted uterine contraction. Affective disorders and malignancies may be other conditions which benefit from calcium antagonist therapy. Calcium antagonists, in particular nimodipine which is most selective for the cerebral vasculature, have been approved for treating vasospasm after subarachnoid haemorrhage. They are probably also effective for treatment of migraine. Calcium channel blockers may be effective for treating acute cerebral infarction, but results of clinical trials to date have been equivocal, largely because it has been difficult to recruit patients within the short interval after the onset of stroke when these drugs would be most effective, and because of the unwanted hypotensive effect of high doses.

Animals↗
PubMed2002

[T-type calcium channel blockers].

T-type calcium channels play an important role in regulating cell function in various kinds of organs, especially in cardiovascular systems. They have been recently clarified to be involved in various pathophysiological conditions, and clinically used for treatment of a variety of diseases. This review reports the usefulness and safety of the T-type calcium channel blockers.

English Abstract↗
PubMed1987

Analgesic effects of several calcium channel blockers in mice.

The possibility that calcium channel blockers might produce antinociception and increase morphine analgesia was examined using the acetic acid writhing test in mice. Subcutaneous injections of diltiazem, verapamil, nicardipine, flunarizine and cinnarizine produced a dose-dependent antinociception. This activity of diltiazem was stereospecific; d-cis-diltiazem was more potent than 1-cis-diltiazem. All the calcium channel blockers studied increased morphine analgesia and displaced to the left the morphine dose-response curve. This effect of diltiazem was also stereospecific. These results suggest that calcium channel blockers can induce analgesia and increase morphine analgesia, possibly through a decrease in cellular calcium availability.

Analgesics↗
PubMed2005

Divergent action of calcium channel blockers on ATP-binding cassette protein expression.

Calcium channel blockers (CCBs) are widely used in clinical practice, and have been reported to be effective in preventing the progression of atherosclerosis. We examined whether various types of calcium channel blockers affected the expression of ATP binding cassette transporter A1 (ABCA1), a factor contributing to anti-atherogenesis. Undifferentiated monocytic cell line, THP-1 cells were maintained in RPMI 1640 medium and treated with different kinds of calcium channel blockers. Among the calcium channel blockers tested, aranidipine and efonidipine increased ABCA1 protein expression without an increase in ABCA1 mRNA expression, whereas other calcium channel blockers (eg, nifedipine, amlodipine, and nicardipine) or T-type calcium channel blockers (eg, mibefradil and nickel chloride) failed to upregulate ABCA1 expression. H89, a protein kinase A inhibitor inhibited the aranidipine-induced ABCA1 protein expression, whereas genistein (a tyrosine kinase inhibitor), or AG490 (a JAK-2 inhibitor) had no effects. Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression. Intracellular cAMP levels were elevated only by aranidipine, but not by efonidipine. In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation. This non-class effect of calcium channel blockers may potentially offer beneficial action in the treatment of hypertensive subjects with atherosclerosis.

ATP Binding Cassette Transporter 1↗
PubMed1998

Prospective study of calcium channel blocker use, cardiovascular disease, and total mortality among hypertensive women: the Nurses' Health Study.

BACKGROUND: In several observational studies, patients prescribed calcium channel blockers had higher risks of cardiovascular diseases and mortality than those prescribed other antihypertensive medications. We explored these associations in the Nurses' Health Study. METHODS AND RESULTS: A total of 14 617 women who reported hypertension and regular use of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, or a combination in 1988 were included in the analyses. Cardiovascular events and deaths were ascertained through May 1, 1994. We documented 234 cases of myocardial infarction. Calcium channel blocker monodrug users had an age-adjusted relative risk (RR) of myocardial infarction of 2.36 (95% CI, 1.43 to 3.91) compared with those prescribed thiazide diuretics. Women prescribed calcium channel blockers had a higher prevalence of ischemic heart disease. After adjustment for these and other coronary risk factors, the RR was 1.64 (95% CI, 0.97 to 2.77). Comparing the use of any calcium channel blocker (monodrug and multidrug users) with that of any other antihypertensive agent, the adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between calcium channel blocker use and myocardial infarction was apparent among women who had ever smoked cigarettes (covariate-adjusted RR, 1.81; 95% CI, 1.20 to 2.72) but not among never-smokers (RR, 0.94; 95% CI, 0.48 to 1.84). CONCLUSIONS: In analyses adjusted only for age, we found a significant elevation in RR of total myocardial infarction among women who used calcium channel blockers compared with those who did not. After adjustment for comorbidity and other covariates, the RR was reduced. Whether the remaining observed elevated risk is real, or a result of residual confounding by indication, or chance, or a combination of the above cannot be evaluated with certainty on the basis of these observational data.

Adult↗
PubMed1994

Concomitant use of nitrates, calcium channel blockers, and beta blockers for optimal antianginal therapy.

Despite the introduction of new mechanical techniques for revascularization, pharmacologic therapy continues to be the mainstay of antianginal therapy. The conventional antianginal medications, which include nitrates, beta blockers, and calcium channel blockers, act to correct the imbalance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. All three are appropriate for the management of angina caused by a fixed coronary obstruction, but nitrates and calcium channel blockers, which not only reduce demand but also increase supply, are preferred in cases of angina believed to involve a significant increase in vasomotor tone. Because of the different yet complementary mechanisms of action of the three classes of anti-ischemic drugs, use of these agents in combination is a rational approach to the treatment of angina unresponsive to monotherapy. Such combinations have been shown to enhance the therapeutic response achieved with single-agent therapy. In addition, the pharmacologic action of one of the components of the combination regimen may serve to offset side effects typically associated with the other.

Adrenergic beta-Antagonists↗
PubMed2002

Differential effects of organic calcium-channel blockers on diastolic SR calcium-handling in the frog heart.

1. Gradual loss of sarcoplasmic reticular (SR) calcium during a rest-period is responsible for the rest-induced decay (RID) of force in mammalian myocardium. Effect of verapamil and diltiazem on a similar RID in the frog myocardium suggests a new mechanism of action of these drugs. 2. Strips of frog-ventricle were paced at 0.2 Hz and the rhythm was interrupted by varying rest-periods ranging from 10 to 180 s. In control conditions, the amplitude of the post-rest beat was significantly lower than that of the pre-rest beat for rest-periods more than 40 s (RID). 3. Verapamil and diltiazem (which are organic calcium-channel blockers (OCCB)) changed the pattern of RID in the control solution to a 'rest-induced potentiation' (RIP) in the same preparation while another OCCB nifedipine and the inorganic calcium-channel blocker cadmium did not alter the post-rest phenomenon. 4. We propose that verapamil and diltiazem produce an RIP due to either blockade of SR calcium-leak during rest or enhancement of SR calcium-uptake during rest.

Animals↗
PubMed2005

Has the controversy over the use of calcium channel blockers in coronary artery disease been resolved?

Calcium channel blockers are used in the treatment of hypertension and angina. The negative findings on cardiovascular outcomes with some short-acting formulations of calcium channel blockers, described in the 1990s, have led to a much reduced use of calcium channel blockers in general. A Coronary disease Trial Investigating Outcome with Nifedipine (ACTION) investigated the effects of the long-acting gastrointestinal therapeutic system (GITS) formulation of nifedipine in patients with stable symptomatic coronary artery disease. There was less new overt heart failure in the nifedipine GITS group (117 of 3825 patients) than in the placebo group (158 of 3840), and coronary angiography and coronary bypass surgery were also lower in the nifedipine GITS than placebo group. Peripheral revascularisation was slightly higher in the nifedipine GITS (187/3825) than the placebo group (144/3840). The Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trial compared a calcium channel blocker (amlodipine) and angiotensin-converting enzyme inhibitor (enalapril) in normotensive patients with coronary artery disease. The primary outcome of cardiovascular events occurred in 151 (23.1%), 110 (16.6%) and 136 (20.2%) of placebo, amlodipine and enalapril patients, respectively, with the only significant difference being a reduction with amlodipine compared with placebo. This reduction mainly represented a reduction in coronary revascularisation and hospitalisation for angina with amlodipine compared with placebo. These results suggest that calcium channel blockers are safe and beneficial in the treatment of coronary artery disease.

Calcium Channel Blockers↗
PubMed1983

Slow calcium channel blockers and the calcium paradox: comparative studies in the rat with seven drugs.

In studies of the calcium paradox, the isolated perfused rat heart was used to characterize the relationship between myocardial protein leakage and the concentration of calcium antagonist (verapamil and D600) or calcium in the perfusion fluid during a cycle of calcium depletion and repletion. The results indicated a dose-dependency such that protein leakage could be progressively reduced by decreasing the concentration of calcium during calcium repletion and/or by increasing the concentrations of drug. Detailed dose-response studies with seven calcium antagonists (verapamil, D600, nifedipine, terodiline, diltiazem, fendiline and prenylamine) and a calcium concentration of 1.0 mmol/l during a 20 min period of calcium repletion following a 10 min period of calcium depletion revealed complex dose-response characteristics for each drug. In the dose range studied (0 to 40 mumol/l) all drugs with the exception of prenylamine were able to reduce protein leakage by up to 25 to 30% Optimal concentrations for verapamil, nifedipine, D600, diltiazem and terodiline were all between 2.0 and 4.0 mumol/l. With the exception of D600, which provided a constant reduction of protein leakage at all concentrations above this optimum, all drugs exhibited bell-shaped dose-response curves with a loss of efficacy at higher concentrations. Fendiline also had a bell-shaped dose-response curve with 23% as a maximal reduction of leakage; however, the optimal concentration for this drug was 21.0 mumol/l. Additional studies with verapamil revealed that the drug acted during the calcium repletion phase and did not influence events during calcium depletion. Simultaneous use of two drugs, verapamil and nifedipine, at their optimal concentrations failed to improve the reduction in protein leakage over and above that observed with one drug alone.

Animals↗
PubMed1996

Effect of calcium-channel blockers on calcium-phosphate metabolism in patients with end-stage renal disease.

BACKGROUND: After EDTA-induced hypocalcaemia, healthy volunteers treated with diltiazem display more severe hyperparathyroidism than subjects on felodipine studied under identical conditions. Therefore patients with end-stage renal disease (ESRD) and severe secondary hyperparathyroidism might be particularly sensitive to this side-effect. METHODS: To test this hypothesis, seven patients with ESRD on chronic haemodialysis (3 women and 4 men) with serum levels of intact PTH ranging from 204 to 675 pg/ml were studied both before and during the first 180 min of haemodialysis against a dialysate with low calcium concentration (0.75 mmol/l, n = 6 and 1 mmol/l, n = 1) under the following three experimental conditions: control, felodipine (10 mg/day) and diltiazem (120 mg b.i.d.). RESULTS: At onset of dialysis, plasma phosphorus level was higher on diltiazem (2.03 +/- 0.08 mM) than on felodipine (1.64 +/- 0.10, P < 0.02), and on the latter it was lower than in control condition (1.88 +/- 0.16, P < 0.02). As a probable consequence, blood ionized calcium concentration was lower on diltiazem (1.14 mM +/- 0.02, mean +/- SEM) than on felodipine (1.2 +/- 0.03, P < 0.05) or in control condition (1.17 +/- 0.01, NS). There was a trend for intact PTH to be higher on diltiazem (324 +/- 47 pg/ml) than on felodipine (246 +/- 55) or in control condition (305 +/- 49) and 1,25-dihydroxyvitamin D was higher indeed on diltiazem (6.70 +/- 0.92 pg/ml) than on felodipine (4.75 +/- 0.91, P < 0.02) or control (3.87 +/- 0.62, P < 0.05). Area under the curve PTH over the first 60 min of dialysis was higher by 16 +/- 7% on diltiazem than on felodipine (P < 0.05). CONCLUSIONS: While on diltiazem rather than on felodipine, patients with ESRD display higher plasma phosphorus levels, and slightly aggravate the degree of severity of hyperparathyroidism recorded during haemodialysis against low-calcium dialysate. The long-term effect of this new observation remains to be evaluated.

Aged↗
PubMed2005

[Calcium channel blockers and bone metabolism].

The effects of calcium channel blockers have been studied on calcitropic hormones and cells involved in bone turnover, osteoblasts and osteoclasts. The secretion of parathyroid hormone is affected by calcium channel blockers, but the modes of action seem to depend upon the species of calcium channel blockers. Generally, overall effects of calcium channel blockers on bone metabolisms and bone mineral density should be trivial and the adverse side effects in this field must be negate. Recent development of a new analogue which may act on the calcium channel of osteoblasts and enhance the differentiation of these cells is intriguing.

Animals↗
PubMed1988

Fundamentals of calcium channel blockers.

The important role calcium ions play in cellular function and specifically in muscular contraction has been well established. The details of the calcium migration into the cell and its specific mechanism of action however have only recently been elucidated. Still, our current understanding of these issues represents only a tip of the iceberg. The introduction of the calcium channel blockers have heralded to some extent a new revolution in the management of many cellular disfunctions (disease states) which are, in part, related to and are dependent on the migration of calcium ions across the cell membrane. In this article, an overview of the current understanding of the role of calcium ions in cellular function with special attention to the cardiovascular system is presented. In addition, the mechanism of action of the calcium channel blockers is discussed. Finally, the usefulness of these agents in clinical medicine is mentioned, and a review of several major studies demonstrating beneficial effects of calcium channel blockers in various disorders is presented.

Angina Pectoris↗
PubMed1996

Mechanism of the antiischemic effect of mibefradil, a selective T calcium channel blocker in dogs: comparison with amlodipine.

Calcium channel blockers are active in variant angina principally by preventing coronary vasospasm. However, a direct antiischemic effect may also occur. In open-chest dogs, an attack of variant angina was mimicked by a 2-min critical coronary stenosis, and the following reversible myocardial ischemia was assessed by measuring the decrease of segmental shortening. We compared the antiischemic mechanism of mibefradil, a T and L calcium channel blocker, with that of amlodipine, a pure L channel blocker. Both drugs showed a similar relationship between the decrease of the rate-pressure product and the antiischemic effect, but only mibefradil reduced heart rate. Amlodipine and mibefradil at the highest doses tested (20 and 70 micrograms/kg/min, respectively) restored 68 +/- 8 and 76 +/- 5% of segmental shortening in the ischemic area, respectively, as compared with preischemic values. Matching blood pressure (by intraaortic balloon) or heart rate (by atrial pacing) to predrug values showed that the antiischemic effect was mainly afterload-dependent for amlodipine and heart rate-dependent for mibefradil. We conclude that in variant angina, in addition to their antivasospastic effects, calcium channel blockers may be antiischemic by a direct myocardial effect associated with a decrease of the rate pressure product. Blockade of the T channel does not seem to participate in the direct antiischemic effect of mibefradil but could explain the decrease of heart rate.

Amlodipine↗
PubMed2000

Calcium channel blockers for potential impaired fetal growth.

BACKGROUND: Calcium channel blockers may increase the blood flow to the fetus or may improve fetal-placental cellular energy generation. This could enhance fetal growth. OBJECTIVES: The objectives of this review were to assess the effects of calcium channel blockers on fetal growth and neonatal morbidity and mortality in pregnancies where impaired fetal growth is suspected. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of the last search: December 1999. SELECTION CRITERIA: Acceptably controlled trials of calcium channel blockers in women with potential impaired fetal growth. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. MAIN RESULTS: One study of 100 women (all smokers) was included. Mean birth weight was significantly higher in women receiving flunarizine compared to the control group. No other significant differences were found. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the use of calcium channel blockers for impaired fetal growth. The apparent beneficial effect of calcium channel blockers on birthweight warrants further investigation.

Calcium Channel Blockers↗