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At least 865 records · Page 48Linked to original sources
PubMed1996

The potential synergistic effect of calcium channel blockers and alpha-tocopherol on gastric mucosal injury induced by ischaemia-reperfusion.

METHODS AND RESULTS: Acute oral administration of various doses of alpha-tocopherol (100, 600, 1200 mg/kg by mouth) produced a dose dependent and significant protection of mucosal injury induced by ischaemia-reperfusion injury in experimental animals. In addition, intraperitoneal administration of calcium channel blockers, nifedipine (0.5, 1, 3 mg/kg), diltiazem (1.25, 2.5 mg/kg) and verapamil (1.25, 2.5, 5, 10 mg/kg) protected gastric mucosa in ischaemia-reperfusion. alpha-Tocopherol (100 mg/kg by mouth), when given in combination with either nifedipine (0.5 mg/kg intraperitoneally), diltiazem (1.25 mg/kg intraperitoneally) or verapamil (1.25 mg/kg intraperitoneally), significantly reduced gastric mucosal injury. The protective effect of calcium channel blockers and the antioxidant agent was synergistic. CONCLUSION: The results showed that calcium channel blockers potentiate the protective effect of the antioxidant activity of alpha-tocopherol on gastric mucosal injury induced by ischaemia-reperfusion in experimental animals.

Administration, Oral↗
PubMed1991

Calcium channel blockers and prostaglandin generation by gastric surface epithelial cells.

We investigated the effects of calcium channel blockers on generation of prostaglandin (PG) E2 and 6-keto PGF1 alpha by gastric mucosal surface epithelium. Surface epithelial cells (SEC) isolated from rat gastric mucosa were incubated with either verapamil (1 or 10 micrograms/ml), diltiazem (2.5 or 25 micrograms/ml) or nifedipine (2.5 or 25 micrograms/ml) for 30 min at 37 degrees C in calcium containing or calcium-free medium. Verapamil (both doses) significantly increased PGE2 and 6-keto PGF1 alpha generation by the surface epithelial cells but only in calcium containing medium. Diltiazem did not affect PG generation in calcium containing nor calcium-free medium. Nifedipine 25 micrograms/ml decreased PGE2 but increased 6-keto PGF1 alpha generation. The inhibitory effect of nifedipine on PGE2 generation was abolished in calcium-free medium, while the calmodulin antagonist did not affect verapamil-induced increase in PG generation.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Effects of calcium channel blockers on neurologic outcome after focal ischemia in rabbits.

To determine the efficacy of calcium channel blockers in preserving neurologic function after central nervous system ischemia, we studied three such agents in two animal models. We treated rabbits after inducing ischemia in the brain with intra-arterial microspheres and in the spinal cord using a removable aortic occluding device. We found no benefit, in terms of neurologic functional outcome, from lidoflazine, nimodipine, or nicardipine. All three agents elevated regional blood flow in the spinal cord. We conclude that calcium antagonists are not likely to prove beneficial if used alone in the treatment of focal central nervous system ischemia.

Animals↗
PubMed2005

Isradipine--a calcium channel blocker--does not potentiate chloroquine antiplasmodial activity against Plasmodium falciparum.

Culturing fresh clinical isolates of P. falciparum and using the isotopic method, we tested separately chloroquine and isradipine--a calcium channel blocker--, and also the combination isradipine plus chloroquine. Tested wild isolates were chloroquine-sensitive. With regard to the combination isradipine/chloroquine, the isobolograms obtained indicate that isradipine antagonises chloroquine antiplasmodial activity. Taking into account these findings, we discuss the issues related to the calcium channel blocker molecules.

Animals↗
PubMed1985

Calcium-channel blockers in the treatment of migraine.

According to classic theory, a migraine attack is initiated by cerebrovascular spasm followed by extracranial vasodilatation. Results of recent studies support this theory and suggest that cerebral blood flow during the initial phase of migraine symptoms is, in fact, decreased and this decrease probably leads to ischemia and hypoxia. Cellular hypoxia, in turn, can cause an increase in the flow of calcium from the extracellular fluid to the intracellular space, resulting in calcium overload and cellular dysfunction. Because calcium-channel blockers selectively inhibit the intracellular influx of calcium ions, investigators have begun evaluating the efficacy of these agents for migraine prophylaxis. Nimodipine, a calcium-channel blocker that exhibits selective effects on cerebral vessels, seems to offer protection against the cerebral ischemia and hypoxia presumed to be operative during migraine attacks. In a double-blind, placebo-controlled study, nimodipine decreased the frequency and duration of migraine attacks by at least half in 69% of patients treated with this agent. Comparable reductions in migraine frequency and duration were attained in 58, 51, 41 and 52% of patients treated with methysergide maleate, pizotifen, clonidine hydrochloride and propranolol, respectively. The piperazine derivative flunarizine also has calcium-channel blocking properties. This agent prevents vasospasm in cerebral arteries and protects against cerebral hypoxia. Results of double-blind studies of migraine prophylaxis with flunarizine demonstrate the beneficial effects of this agent, particularly in younger patients. Flunarizine proved to be superior to pizotifen in decreasing the severity of migraine attacks and comparable to pizotifen in decreasing their frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗
PubMed2002

Calcium channel blockers as first line treatment for broad complex tachycardia with right bundle branch block: ingenuity or folly?

OBJECTIVE: To study the response of regular broad-complex tachycardia (BCT) demonstrating right bundle branch block (RBBB) to treatment in the Emergency department (ED). METHODS: Retrospective chart review of management of patients with BCT, RBBB without a history of ischaemic heart disease. A diagnosis of ventricular tachycardia (VT) was made if the ECG showed features such as atrioventricular dissociation, capture or fusion beats or if VT was demonstrated during electrophysiological studies (EPS). RESULTS: A total of 25 patients were eligible. Nineteen patients were given intravenous (IV) calcium channel blockers (either verapamil or diltiazem), as first line treatment. Of these, 18 converted to sinus rhythm and the other one patient subsequently converted with amiodarone. The remaining six patients were given IV adenosine (n=3), lignocaine (n=2) or amiodarone (n=1) as first line treatment but none of them were converted. Of these, four of them converted with IV calcium channel blockers eventually. Of the other two patients, who were both given lignocaine initially, one deteriorated haemodynamically with the use of verapamil and required synchronised cardioversion to convert. The other patient did not respond to amiodarone and synchronised cardioversion but was subsequently converted with verapamil. The difference between the success rate of calcium channel blockers and other anti-arrhythmics is statistically significant (P<0.01 by Fischer's exact method). Fourteen cases had diagnoses of VT, including the two patients given lignocaine. Five cases were found to have supraventricular tachycardia with aberrant conduction. Six cases did not have confirmed diagnoses. CONCLUSION: In patients presenting with BCT and RBBB but without underlying ischaemic heart disease, there is evidence to suggest that calcium channel blockers could effectively be used as the treatment of choice.

Adult↗
PubMed1999

[Use of calcium channel blockers for prophylaxis of multiple organ failure in acute destructive pancreatitis].

The purpose of this study was to investigate effectiveness of the usage of calcium channels blockers and plasmaleukopheresis in prophylaxis of the syndrome of polyorganic insufficiency (SPI) in patients with acute destructive pancreatitis. 30 patients operated on for pancreonecrosis were divided into 2 groups: study group (13 patients) and control one (17 patients) matched for sex, age, extent and character of changes in the pancreas. Taking into account a substantial role of hyperactive neutrophils in pathogenesis of SPI, Verapamil (dose of 0.5 mg/kg/day) and discrete plasmaleukopheresis were included in the complex of treatment for patients of the study group. Effectiveness of the treatment was assessed according to the quantity of complications, lethality values of leukocytosis and leukocyte index of intoxication (LII) as well as by the scale of the severity of sepsis (SSS). Complicated postoperative course was seen in 41.18% of cases in the control group and 23.07%--in the study one. Lethality in the control group made up 11.8% (2 patients); there were no lethal outcomes in the study group. Anearlier decrease in leukocytes count, LII and SSS in the study group was significant. The conclusion is made on effectiveness of the use of calcium channels blockers and discrete plasmaleukopheresis for prophylaxis of SPI in acute destructive pancreatitis.

Adult↗
PubMed1985

Inhibition of macrophage activation by calcium channel blockers and calmodulin antagonists.

The biochemical mechanisms by which macrophages become activated to the tumoricidal state are poorly understood. To investigate the role of calcium in this process, the effect of calcium channel blockers and calmodulin antagonists on the acquisition of tumoricidal properties by macrophages activated by a number of different agents was examined. Activation of thioglycollate-stimulated C57BL/6 mouse peritoneal macrophages by macrophage activation factor (MAF) plus LPS, IFN-gamma plus LPS or the calcium ionophore, A23187, was inhibited in a dose-dependent fashion by the calcium channel blockers nifedipine and verapamil. These agents blocked the influx of 45Ca into macrophages activated by MAF plus LPS. Macrophage activation was also inhibited by chlorpromazine, W-7, and calmidazolium at concentrations known to perturb calmodulin function. The data suggest that activation of macrophages to the tumoricidal state is a calcium-dependent process involving the participation of calcium-regulated biochemical reactions whose activities can be modulated by pharmacological agents that frustrate transmembrane calcium fluxes and/or inhibit calmodulin function.

Animals↗
PubMed1987

Codeine-induced mast cell degranulation in human skin: effect of calcium channel blockers.

Codeine and other opiates can induce immediate type wheal and flare skin reactions. Calcium channel blockers including nifedipine have been shown to inhibit mast cell degranulation in different systems. The oral administration of nifedipine (10 mg) did not affect the size of codeine-induced skin reactions in ten normal volunteers. Mean wheal over flare sizes were 11.7 mm/29.2 mm before nifedipine and 11.5 mm/31.0 mm at peak nifedipine blood levels. Similar observations were made when codeine was injected locally with or without 20 micrograms nifedipine (12.1/29.2 mm and 13.2/29.2 mm, respectively). These data suggest that codeine-induced mast cell degranulation may be mediated by a calcium-independent mechanism. Alternatively, mast cells in the human skin may differ in their reactions to secretagogues when compared with basophils and mast cells from other human tissues or other species.

Adult↗
PubMed1993

Characterization of calcium channel blocker induced smooth muscle relaxation using a model of isolated corpus cavernosum.

Several classes of smooth muscle relaxing agents have proven effective in relaxing cavernosal smooth muscle and useful in the pharmacotherapy of erectile dysfunction. The purpose of this investigation was to determine whether the calcium channel blockers (CCB) relax cavernosal smooth muscle. Thirty-two rabbit cavernosal strips were contracted by electrical field stimulation, and contraction inhibition was tested in response to cumulative doses (10(-8) M. to 10(-4) M.) of verapamil (V), diltiazem (D), isradipine (I), nicardipine (Nc) and nifedipine (Nf). All of the calcium channel blockers were effective at inhibiting electrically induced contractions (p < 0.0001 when CCB was compared with control; p < 0.05 when V or D was compared with I, Nc or Nf). Sixteen cavernosal strips were precontracted with 10(-5) M. norepinephrine. Relaxation in response to cumulative doses of each CCB was determined. Verapamil and the dihydropyridines (isradipine, nicardipine and nifedipine), but not diltiazem, were effective at relaxing norepinephrine induced contractions at 10(-5) and 10(-4) M. with verapamil most effective at 10(-4) M. concentration (p < 0.0001 by ANOVA at both concentrations when V, I, Nc, or Nf was compared with control). Sixteen cavernosal strips were incubated in solutions of 10(-5) and 10(-4) M. of each CCB followed by cumulative addition of norepinephrine (concentration range 10(-8) to 10(-4) M.). Preincubation with CCB did not affect the concentration of norepinephrine at which 50% of maximal cavernosal contractile response occurred (ED50). Maximum active tension of norepinephrine induced contractions was moderately decreased after CCB preincubation with 10(-4) M. of each dihydropyridine. It is concluded that the calcium channel blockers are effective in relaxing cavernosal smooth muscle and therefore possess potential as intracavernous pharmacotherapeutic agents for the treatment of erectile dysfunction. Verapamil appears to be the best candidate for further testing and clinical trial.

Animals↗
PubMed2004

Screening for dihydropyridine calcium channel blockers in plasma by automated solid-phase extraction and liquid chromatography/tandem mass spectrometry.

A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) screening method was developed for the screening of 11 calcium channel blockers of the 1,4-dihydropyridine type in plasma samples for forensic and clinical cases. Plasma samples were extracted by automated solid-phase extraction. Analysis was performed using a reversed-phase C(18) column, gradient elution and a triple-quadrupole mass spectrometer with TurboIonSpray source in positive mode and multiple reaction monitoring. This method was found to be selective and sensitive for the detection of the target compounds at their therapeutic plasma concentrations.

Automation↗
PubMed1996

Interaction of calcium channel blockers with different agonists in aorta from normal and diseased rats.

The interactions of calcium channel blockers (CCBs) with noradrenaline (NA), phenylephrine (PE), dopamine (DA) and KCl have been investigated in rat isolated aortic strip. In preparations from control and hypertensive (DOCA-saline) rats chronically treated with verapamil, nifedipine and diltiazem, there was partial inhibition of contractions to NA, PE and DA. However, with nimodipine, there was potentiation of responses. This could be related to the occurrence of different isoforms of L-type calcium channels. In preparations obtained from hyperthyroid rats the concentration-response curves of NA, PE and KCl were shifted to the right with depressed maximal response which could be secondary to the primary effect exerted on the heart. In preparations from L-thyroxine + nimodipine/nifedipine treated rats the concentration-response curves of NA, PE and KCl were shifted to the right and the maxima was depressed suggesting that this may be due to decreased alpha receptor density (NA and PE) and down-regulation of voltage operated channels (KCl).

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Experimental research on the effect of calcium channel blockers nifedipine and verapamil on the anxiety in mice.

The anxiolytic effect of the calcium channel blockers nifedipine and verapamil was tested in mice using two test: the conditioned suppression of the motility test and the black and white box test. The nifedipine but not the verapamil, in low doses (0.1 mg/kg b.w), proved anxiolytic effect and both nifedipine and verapamil in high dose (1.6-2.5 mg/kg b.w) had anxiogenic properties. The anxiogenic effect was correlated with the capacity of the drugs to block the calcium channels and the anxiolytic effect of low doses of the nifedipine was considered to be produced by opening these structures. These data were considered important for a new future aboard of the treatment and pathophysiology of the anxiety.

Analysis of Variance↗
PubMed1990

Therapeutic considerations in the elderly hypertensive. The role of calcium channel blockers.

Hypertension is an extremely common problem in the elderly. The optimum antihypertensive agent to use in this population is not certain. In this paper, the factors influencing the choice of antihypertensive therapy are reviewed. They include efficacy, safety, comorbidity, utility in special populations, drug interaction, dosage schedule, cost, the mechanisms of action of the drug, and the pathophysiology of the patient's hypertension. Calcium channel blockers are effective and safe in the elderly. They improve other conditions frequently seen in that population and, with the exception of cardiac conduction abnormalities associated with some calcium channel blockers, do not adversely affect other comorbid diseases. They work well together with other antihypertensives and as vasodilators, they may be specifically appropriate in elderly hypertensives, whose hypertension is associated with reduced cardiac output and increased peripheral vascular resistance. Once- and twice-a-day preparations are available to foster compliance, but calcium channel blockers are expensive.

Aging↗
PubMed2002

Trends in consumption of calcium channel blockers in the Czech Republic during 1993-1999 and comparison with selected countries: drug utilization study.

OBJECTIVE: To determine the patterns of consumption in calcium channel blockers (CCB) groups in the Czech Republic between 1992 and 1999 and make a comparison with selected countries. METHODS: This was part of a drug utilization study using WHO methodology [Anatomical Therapeutic Chemical classification/defined daily doses (ATC/DDD)]. The wholesale data collected by drug distributors were used. Utilization was calculated as the DDDs for 1000 inhabitants per day. In focus was the consumption of short-acting nifedipine. Comparison with wholesale data from Finland, Norway, Germany and Australia was made. RESULTS: There was a decreasing tendency to use short-acting nifedipine in the Czech Republic over the period 1993-1999. Four years after publication of warning evidence, short-acting nifedipine still accounted for 23% of all calcium channel blockers in our country. The abundance of second-generation CCBs increased from less than 1% in 1993 to 43% in 1999. The consumption of short-acting nifedipine in the Czech Republic and Germany is probably three times more frequent than in Nordic countries and Australia. CONCLUSIONS: Consumption of short-acting nifedipine in the Czech Republic 4 years after recognition of its risks still remains very high. This suggests that implementation of clinical trial results to clinical practice is very slow and ineffective.

Calcium Channel Blockers↗
PubMed1989

Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro.

The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [3H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that verapamil (10(-4)-10(-5) M) and nimodipine (10(-4)-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by simultaneous addition of calcium chloride (5 x 10(-3) M). These results indicate that verapamil and nimodipine may exert an antiproliferative effect on glioma cells growth acting through a blockade of specific voltage-dependent calcium channels.

Calcium↗
PubMed1990

Chromatography of calcium channel blockers.

Numerous publications during the past ten years have described the determination of various calcium channel blockers in biological fluids, using gas and liquid chromatographic techniques. Diltiazem, verapamil, flunarizine and a growing number of dihydropyridines belong to this group of drugs, which in most instances are active at low plasma concentrations. From a bioanalytical point of view these compounds have many features in common, such as high lipophilicity and favourable detection properties.

Body Fluids↗