Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Calcium Channel Blockers”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed1997

Hepatotoxicity of ethanol: protective effect of calcium channel blockers in isolated hepatocytes.

This study examines the effects of three calcium channel blockers (verapamil, nifedipine and diltiazem) on isolated rat hepatocytes exposed to ethanol. In the first part of our study, hepatocytes were incubated with increasing concentrations of ethanol (100, 300, 500, 1000 mM) for varying times. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) release were measured to evaluate the cytotoxic effects of ethanol. The concentration of 300 mM and time of incubation of 45 min were chosen for cytoprotection experiments in which calcium channel blockers, at two different concentrations, were added to the medium 30 min prior to the addition of ethanol. ALT, AST and LDH release as well as lipid peroxidation and cellular reduced glutathione (GSH) were measured. Nifedipine and verapamil (25 microM) reduced ALT, AST and LDH activities. The highest dose of diltiazem (50 microM) was more effective than the lowest one (25 microM). Ethanol caused a significant depletion of cellular GSH content as well as a moderate enhancement of lipid peroxidation. While none of the three calcium channel blockers was able to restore the decrease in GSH levels, diltiazem (25 microM) and nifedipine (50 microM) showed the greatest effect, significantly reducing lipid peroxidation.

Animals↗
PubMed1989

Effect of MCI-176, a new calcium channel blocker, on large and small coronary arteries in dogs.

MCI-176, a new calcium channel blocker, increases coronary blood flow and may improve perfusion in ischaemic areas. Its vasodilating effects on large conductive coronary arteries and the resistive arterioles were therefore compared with those of diltiazem, nifedipine, glyceryl trinitrate and adenosine in anaesthetised open chest beagle dogs. Intracoronary injection of these compounds caused dose dependent increases in coronary flow associated with decreases in the resistance of resistive arterioles, and the rank order of potency was nifedipine greater than adenosine greater than MCI-176 greater than diltiazem greater than glyceryl trinitrate. The resistance of the large conductive vessels was likewise reduced by these agents, except for adenosine. Glyceryl trinitrate showed the highest selectivity to the large conductive vessels, while adenosine showed the lowest and calcium channel blockers were intermediate. Among three calcium channel blockers, MCI-176 had the highest selectivity to the large conductive vessels, while the duration of action was the longest with diltiazem; the duration of action of MCI-176 was intermediate. Thus, MCI-176 is a coronary vasodilator, the potency of which is intermediate between nifedipine and diltiazem, but it has the highest selectivity to the large conductive vessels among these three compounds.

Adenosine↗
PubMed2005

Calcium channel blockers and renal protection: insights from the latest clinical trials.

Calcium channel blockers have been widely used in clinical practice because of their antihypertensive capacity. Prevention of renal damage is a very important aim of antihypertensive therapy. This is particularly so taking into account the high prevalence of chronic kidney disease (CKD) in the general population. Recent data have shown that CKD is related to the absence of adequate BP control and also to the clustering of other cardiovascular risk factors seen in the metabolic syndrome. The knowledge of the capacities of the different antihypertensive drugs or their combinations to simultaneously control BP while protecting the kidney and avoiding the facilitation of metabolic alterations is warranted. Recent data from the Intervention as a Goal in Hypertension Treatment trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and African American Study of Kidney Disease and Hypertension (AASK) allow the conclusion that in hypertensive patients with preserved renal function or with CKD, calcium channel blockers are effective antihypertensive drugs to be considered alone or in combination with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.

Calcium Channel Blockers↗
PubMed1996

Potentiation of local lignocaine-induced sensory block by calcium channel blockers in rats.

We have studied the effects of three different types of calcium channel blockers (verapamil, diltiazem, and nicardipine) on local lignocaine sensory block. The standardized tail flick test was used to measure the duration and degree of lignocaine-induced conduction block in rats. After obtaining baseline tail flick latencies (mean 3.2 s), two 100-microliter doses of 0.3% lignocaine alone, a combination of verapamil 25, 100 or 200 micrograms, diltiazem 25, 100 or 200 micrograms, or nicardipine 0.5, 1.0 or 2.0 micrograms, and a large dose of calcium channel blockers (verapamil 200 micrograms, diltiazem 200 micrograms or nicardipine 2.0 micrograms) were injected on opposite sites of the tail base and the tail flick test was performed every 5 min for 45 min. A large dose of the calcium channel blockers showed no prolongation of tail flick latencies. Administration of 0.3% lignocaine alone produced a significant increase in tail flick thresholds and the peak effect of the percentage maximum possible effect (% MPE) was demonstrated at 5 min after drug injection (mean % MPE 28.8%; P < 0.01 vs baseline). Co-administration of 0.3% lignocaine and three doses of verapamil produced significant increases in area under the curve (AUC) in a dose-dependent fashion. Mean AUC values for 0.3% lignocaine alone and a combination of verapamil 25, 100 or 200 micrograms were 217.5, 502.5, 529.1 and 1600.3, respectively. Almost similar patterns of augmentation in AUC values were demonstrated after addition of different doses of diltiazem or nicardipine to 0.3% lignocaine. We conclude that the use of mixtures of local anaesthetic and calcium channel blocker potentiated lignocaine sensory block at the level of the peripheral nerves.

Anesthetics, Local↗
PubMed1990

Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine.

Kupffer cells are activated by calcium and release a variety of toxic mediators, including proteases. The purpose of these studies, therefore, was to determine if protease inhibitors and a calcium channel blocker could increase survival time in the rat model of orthotopic liver transplantation. Survival for 30 days was greater than 90% in this model when livers were stored for 1 hr in Ringer's solution (survival conditions)--however, grafts stored for 4 hr in Euro-Collins solution or 8 hr in University of Wisconsin (UW) solution survived postoperatively only 1.2 and 0.7 days, respectively (nonsurvival conditions). When livers were stored for 4 hr in Euro-Collins containing a cocktail of protease inhibitors (leupeptin, pepstatin A, phenylmethylsulfonyl fluoride, 20 ng/ml each; diisopropyl fluorophosphate, 100 microM) and subsequently transplanted, however, survival time was increased significantly to 11.5 days. Inclusion of a calcium channel blocker, nisoldipine (1.4 microM), in the protease inhibitor cocktail increased survival time to 23 days. Actually, nisoldipine alone increased survival time to 25 days. Nisoldipine alone also increased survival time in livers stored for 8 or 16 hr in UW solution to between 15 and 20 days. Serum transaminase levels reached peak values greater than 2400 U/L one day postoperatively in the nonsurvival groups, and liver injury assessed histologically was apparent. Under these conditions, pulmonary infiltration of inflammatory cells was observed in about 60% of the lungs examined and was associated with massive bleeding. Inclusion of the protease cocktail, nisoldipine, or both in the storage solutions decreased maximal SGOT levels and injury to both liver and lung significantly by about 50% postoperatively. Nisoldipine also decreased phagocytosis of carbon particles by the perfused liver 2- to 3-fold following storage under nonsurvival conditions (half-maximal effect = 0.3-0.4 microM nisoldipine). Moreover, nisoldipine improved hepatic microcirculation. It accelerated blood flow into the liver, as indexed by hemoglobin reflectance from the liver surface. These data support the hypothesis that Kupffer cells are activated early in the sequence of events that causes graft failure leading to endothelial cell-mediated alterations in the microcirculation. This work demonstrates clearly that dihydropyridine-type calcium channel blockers such as nisoldipine may be clinically useful in storage solutions for liver prior to transplantation.

Animals↗
PubMed1999

Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.

OBJECTIVE: Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. SETTING: The New Jersey Medicare population. DESIGN: A retrospective cohort study using linked Medicare and drug claims data. PARTICIPANTS: Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. MEASUREMENTS: The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. RESULTS: Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). CONCLUSION: Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.

Aged↗
PubMed1998

Effect of subcutaneous administration of calcium channel blockers on nerve injury-induced hyperalgesia.

Recent studies suggest that calcium contributes to peripheral neural mechanisms of hyperalgesia associated with nerve damage. In this animal behavioural study, we examined further the contribution of calcium in neuropathic pain by testing whether subcutaneous administration of either a calcium chelating agent or voltage-dependent calcium channel blockers attenuate nerve injury-induced hyperalgesia to mechanical stimulation. Studies were carried out in animals with partially ligated sciatic nerves, an established animal model of neuropathic pain. The nociceptive flexion reflex was quantified using an Ugo Basile Analgesymeter. Partial nerve injury induced a significant decrease in mechanical threshold compared to the sham operated controls. Daily subcutaneous injections of the calcium chelating agent, Quin 2 (20 microgram/2.5 microliter), significantly attenuated the nerve injury-induced hyperalgesia. Similarly, SNX-111, a N-type channel blocker, also significantly attenuated the nerve injury-induced hyperalgesia. SNX-230, a P and/or Q-type channel blocker, and nifedipine, a L-type channel blocker, had no effect on the hyperalgesia to mechanical stimulation. In control experiments, SNX-111 had no effect on mechanical thresholds when administered subcutaneously in either the hindpaw of normal animals or the back of the neck in nerve injury animals. This study shows that neuropathic pain involves a local calcium-dependent mechanism in the receptive field of intact neurons of an injured nerve, since it can be alleviated by subcutaneous injections of either a calcium chelating agent or SNX-111, a N-type calcium channel blocker. These agents may be effective, peripherally acting therapeutic agents for neuropathic pain.

Afferent Pathways↗
PubMed2000

Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension.

The calcium channel blockers (CCBs) are a diverse group of antihypertensive medications with variable pharmacokinetics and clinical effects. Although CCBs have been widely applied to the treatment of hypertensive children, data regarding the pharmacokinetics, efficacy and safety of these agents in children are extremely limited. In this review we briefly summarize the mechanism of action of CCBs and then summarize pertinent pharmacokinetic information on each of the CCBs commonly used in children, including amlodipine, diltiazem, felodipine, isradipine, intravenous nicardipine, nifedipine and verapamil. Clinically important drug interactions and adverse effects are discussed, as well as the potential role of CCBs in renal protection. Available pediatric efficacy and safety data are summarized, and recommendations made regarding the rational use of CCBs in the management of pediatric hypertension.

Calcium Channel Blockers↗
PubMed1987

Calcium-channel blockers for combined systemic hypertension and myocardial ischemia.

Scientific rationale suggests a potentially important role for the calcium-channel blockers in the treatment of patients with coexisting systemic hypertension and coronary artery disease. Clinical investigation confirms the usefulness of these drugs as monotherapy in the treatment of patients with chronic stable angina and mild-to-moderate hypertension. There are several therapeutic effects of the calcium-channel blockers in coronary artery disease. Beneficial actions on the major determinants of oxygen consumption, i.e., heart rate, blood pressure, and contractility, are generally seen. The potent coronary vasodilating actions of these drugs allow for increased coronary blood flow and alleviation of coronary vasospasm. The effectiveness of the calcium-channel blockers in hypertension appears to be primarily due to their ability to induce systemic vasodilation. Improvements in ventricular compliance, regression of left ventricular hypertrophy, and cardioprotection appear to be additional beneficial effects of the drugs. Calcium-channel blockers compare favorably with beta-blockers; they appear to be more effective than some beta-blockers in the treatment of hypertension in the elderly and black population and can be given to patients with bronchospasm or peripheral vascular disease. Calcium-channel blockers are a welcome addition to existing drug regimens available for the management of patients with concomitant coronary artery disease and systemic hypertension.

Angina Pectoris↗
PubMed1991

Influence of calcium channel blockers on polymorphonuclear and monocyte bactericidal and fungicidal activity.

The effect of calcium channel blocking agents on the killing activity of human peritoneal polymorphonuclears (PMN) and monocytes was studied. The organisms used were Escherichia coli, Staphylococcus aureus and Candida albicans. The pharmacological concentration of verapamil (5 microM), nifedipine (10 microM) and diltiazem (10 microM) caused a similar inhibition of killing activity in both PMN and monocytes. The calcium channel blockers significantly reduced the in vitro killing of E. coli, S. aureus and C. albicans by PMN to about 47%, 30% and 20% respectively, compared with 81 +/- 6%, 65 +/- 5% and 40 +/- 4% in the controls. The killing of these organisms by monocytes was 60 +/- 6%, 42 +/- 7% and 35 +/- 5% respectively, as compared with 30%, 20% and 17% in the presence of these drugs. The bactericidal activity of the phagocytic cells from patients under treatment with calcium channel blockers was not affected and was found to be within the normal range, indicating that calcium channel blockers do not cause an irreversible impairment in PMN and monocyte killing activity. However, their potential inhibition of phagocytic cell activity should be taken into consideration during treatment.

Adult↗