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Calcium Channel Blockers (calcium + channel_blocker)
Kinds of Calcium Channel Blockers Selected AbstractsEFFECT OF COMBINATION THERAPY (ANG II ANTAGONIST, VALSARTAN AND A CALCIUM CHANNEL BLOCKER) IN A HYPERTENSIVE MODEL OF DIABETIC NEPHROPATHYNEPHROLOGY, Issue 3 2000Allen Tj Davis Bj [source] N-type Calcium Channel Blocker for Pain TreatmentPAIN MEDICINE, Issue 2 2010Jianren Mao MD No abstract is available for this article. [source] Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on VerapamilJOURNAL OF CLINICAL HYPERTENSION, Issue 2 2007Domenic A. Sica MD In the past 2 decades, calcium channel blockers have emerged as important and useful agents for treating hypertension. The safety of this drug class has been vigorously debated for some time, and it has only been in the past few years that such debate has been quieted by favorable outcomes data with these compounds. Calcium channel blockers are a heterogeneous group of compounds as alike as they are dissimilar. Calcium channel blockers can be separated into dihydropyridine and nondihydropyridine subclasses, with representatives of the latter being verapamil and diltiazem. A lengthy treatment experience exists for verapamil, a compound that has progressed from an immediate-release to a sustained-release and, more recently, a delayed/sustained-release formulation designated for administration at bedtime. This latter formulation synchronizes drug delivery with the early morning rise in blood pressure, which is a particularly attractive feature when viewed in the context of the distinctive pharmacokinetic and pharmacodynamic features of verapamil. [source] Pharmacotherapy Review: Calcium Channel BlockersJOURNAL OF CLINICAL HYPERTENSION, Issue 1 2006Domenic A. Sica MD As a drug class, calcium channel blockers encompass a heterogeneous group of compounds with distinctive structures and pharmacologic characteristics. These agents are widely used in the treatment of hypertension, chronic coronary ischemia, and/or supraventricular arrhythmias. Much of the early debate alluding to increased cardiovascular risk associated with calcium channel blocker use has been silenced by an array of outcomes trials that show these drugs to be both safe and effective in reducing hard cardiovascular end points. The most common side effects associated with calcium channel blockers are vasodilatory in nature and include a non-volume-dependent form of peripheral edema, flushing, and headache. Despite the sometimes discomforting side effects seen with calcium channel blocker therapy, their robust blood pressure-lowering effect makes them an important component of most multidrug regimens used for blood pressure control. [source] Topical Application of Calcium Channel Blockers to Reduce the Progression of Experimentally Induced Myringosclerosis and TympanosclerosisTHE LARYNGOSCOPE, Issue 4 2008Adin Selcuk MD Abstract Objectives: This study aimed to evaluate the ability of topically applied calcium channel blockers (diltiazem) to reduce the progression of experimentally induced myringosclerosis and tympanosclerosis. Study Design: Animal model. Experimental prospective study. Methods: The study included 25 adult albino guinea pigs that were bilaterally myringotomized and inoculated with a suspension of Streptococcus pneumonia type 3. The right ears were treated with topical application of diltiazem, and the untreated left ears served as the control group. Otomicroscopy and remyringotomy were conducted every week. One animal was sacrificed after 1 week and the remaining at the end of 6 weeks. Temporal bones were dissected, and tympanic bullae were analyzed with light microscopy. Results: The untreated control ears showed evidence of extensive myringosclerosis on otomicroscopy, and the ears treated with calcium channel blockers did as well although to a lesser degree. Under light microscopy, the lamina propria of both tympanic membranes and middle ear mucosae of the control group exhibited thicker (P < .1 and P < .05, respectively) and larger (P < .01 and P < .01, respectively) sclerotic tissue in comparison with the treatment group. Conclusion: The results suggest that calcium channel blockers had an influence in the prevention of tympanosclerosis. [source] Calcium Channel Blocker-Related Peripheral Edema: Can It Be Resolved?JOURNAL OF CLINICAL HYPERTENSION, Issue 4 2003Domenic A. Sica MD Calcium channel blocker (CCB)-related edema is quite common in clinical practice and can effectively deter a clinician from continued prescription of these drugs. Its etiology relates to a decrease in arteriolar resistance that goes unmatched in the venous circulation. This disproportionate change in resistance increases hydrostatic pressures in the precapillary circulation and permits fluid shifts into the interstitial compartment. CCB-related edema is more common in women and relates to upright posture, age, and the choice and dose of the CCB. Once present it can be slow to resolve without intervention. A number of strategies exist to treat CCB-related edema, including switching CCB classes, reducing the dosage, and/or adding a known venodilator such as a nitrate, an angiotensin-converting enzyme inhibitor, or an angiotensin-receptor blocker to the treatment regimen. Angiotensin-converting enzyme inhibitors have been best studied in this regard. Diuretics may alter the edema state somewhat, but at the expense of further reducing plasma volume. Traditional measures such as limiting the amount of time that a patient is upright and/or considering use of graduated compression stockings are useful adjunctive therapies. Discontinuing the CCB and switching to an alternative antihypertensive therapy will resolve the edema. [source] A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of ,vascular depression'INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2001Fernando E. Taragano Abstract Background ,Vascular depression' may be caused by cerebrovascular disease. Calcium channel blockers, which are putative treatments for cerebrovascular disease, might be expected to improve depression reduction and to prevent recurrence of depression in this patient population. This clinical trial was designed to test these hypotheses. Design This was a controlled, double blind, randomized clinical trial in which 84 patients with vascular depression (Alexopoulos criteria) were treated with antidepressants at standard doses. Patients were also randomized to nimodipine (n,=,40) or an inactive comparator, vitamin C (n,=,44). Treatment outcomes were assessed using the Hamilton depression rating scale (HDRS) regularly up to 300 days after treatment initiation. Results As expected, depression reduction was successful in most patients. In addition, those treated with nimodipine plus an antidepressant had greater improvements in depression overall in repeated measures ANCOVA (F(1,81),=,8.64, p,=,0.004). As well a greater proportion of nimodipine-treated participants (45 versus 25%) exhibited a full remission (HDRS,,10) (,2(df, 1),=,3.71, p,=,0.054). Among those experiencing a substantial response in the first 60 days (50% reduction in HDRS), fewer patients on nimodipine (7.4%) had a recurrence of major depression when compared to those on antidepressant alone (32%) (,2(df, 1),=,3.59, p,=,0.058). Conclusions In treating vascular depression, augmentation of antidepressant therapy with a calcium-channel blocker leads to greater depression reduction and lower rates of recurrence. These findings support the argument that cerebrovascular disease is involved in the pathogenesis and recurrence of depression in these patients. Copyright © 2001 John Wiley & Sons, Ltd. [source] Calcium channel blockers inhibit galvanotaxis in human keratinocytesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2002Donna R. Trollinger Directed migration of keratinocytes is essential for wound healing. The migration of human keratinocytes in vitro is strongly influenced by the presence of a physiological electric field and these cells migrate towards the negative pole of such a field (galvanotaxis). We have previously shown that the depletion of extracellular calcium blocks the directional migration of cultured human keratinocytes in an electric field (Fang et al., 1998; J Invest Dermatol 111:751,756). Here we further investigate the role of calcium influx on the directionality and migration speed of keratinocytes during electric field exposure with the use of Ca2+ channel blockers. A constant, physiological electric field strength of 100 mV/mm was imposed on the cultured cells for 1 h. To determine the role of calcium influx during galvanotaxis we tested the effects of the voltage-dependent cation channel blockers, verapamil and amiloride, as well as the inorganic Ca2+ channel blockers, Ni2+ and Gd3+ and the Ca2+ substitute, Sr2+, on the speed and directionality of keratinocyte migration during galvanotaxis. Neither amiloride (10 ,M) nor verapamil (10 ,M) had any effect on the galvanotaxis response. Therefore, calcium influx through amiloride-sensitive channels is not required for galvanotaxis, and membrane depolarization via K+ channel activity is also not required. In contrast, Sr2+ (5 mM), Ni2+ (1,5 mM), and Gd3+ (100 ,M) all significantly inhibit the directional migratory response to some degree. While Sr2+ strongly inhibits directed migration, the cells exhibit nearly normal migration speeds. These findings suggest that calcium influx through Ca2+ channels is required for directed migration of keratinocytes during galvanotaxis and that directional migration and migration speed are probably controlled by separate mechanisms. J. Cell. Physiol. 193: 1,9, 2002. © 2002 Wiley-Liss, Inc. [source] Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on VerapamilJOURNAL OF CLINICAL HYPERTENSION, Issue 2 2007Domenic A. Sica MD In the past 2 decades, calcium channel blockers have emerged as important and useful agents for treating hypertension. The safety of this drug class has been vigorously debated for some time, and it has only been in the past few years that such debate has been quieted by favorable outcomes data with these compounds. Calcium channel blockers are a heterogeneous group of compounds as alike as they are dissimilar. Calcium channel blockers can be separated into dihydropyridine and nondihydropyridine subclasses, with representatives of the latter being verapamil and diltiazem. A lengthy treatment experience exists for verapamil, a compound that has progressed from an immediate-release to a sustained-release and, more recently, a delayed/sustained-release formulation designated for administration at bedtime. This latter formulation synchronizes drug delivery with the early morning rise in blood pressure, which is a particularly attractive feature when viewed in the context of the distinctive pharmacokinetic and pharmacodynamic features of verapamil. [source] Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetricsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009M. VERCAUTEREN Aim: Significant side effects of tocolytic and uterotonic substances may be of concern to the anaesthesiologist. Recently, new drugs have been introduced having less side effects for both the mother and the neonate. Methods: A literature search was undertaken mainly focusing on meta-analyses, to review the possible side effects that might affect the course of anaesthesia and to suggest which precautions should be considered to prevent the occurrence of significant interactions with anaesthetic manipulations and drugs. Results: Magnesium sulphate has a proven benefit in lowering systolic blood pressure and preventing the occurrence of eclampsia, but not as a tocolytic. ,-adrenergic agonists are being abandoned due to the availability of tocolytic agents causing less side effects. Calcium channel blockers (CCB) are frequently used but can cause major maternal cardiovascular complications. Nitroglycerin seems to be appreciated as an acute tocolytic rather than a routine substance during pre-term labour. Cyclo-oxygenase-2 inhibitors are still under investigation but their tocolytic benefit is questionable mainly due to foetal side effects. Atosiban is considered the first-choice tocolytic. With respect to oxytocic drugs, oxytocine, prostaglandines and methylergometrine may all cause serious side effects especially when combined. The cardiovascular side effects of prostaglandins and methylergometrine can be life-threatening. Both oxytocin and carbetocin have a rather low risk for maternal complications. Conclusion: Atosiban and CCB are at least as effective tocolytic agents as ,-mimetics but have significantly less side effects. Magnesium sulphate can cause neuromuscular blockade, especially when combined with CCB. Concerning oxytocic agents, short-acting oxyctocin and long-acting carbetocin have the least side effects as compared with prostaglandins and methylergometrine. [source] Adverse effects of tocolytic therapyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2005Steve Caritis The rationale for using tocolytics in preterm labour is to enable transfer of the mother to a tertiary centre and to prolong pregnancy sufficiently so that glucocorticoids can be administered to the mother. There is little question that these short term objectives can be achieved with contemporary tocolytics. Whether tocolytics can maintain pregnancy for sufficient periods to enable in utero maturation to occur remains an unresolved question. When a decision is made to use tocolytics, the clinician is faced with a multitude of choices with side effects, efficacy and ease of administration generally being the most important considerations. Placebo-controlled studies suggest that the ,-agonists, prostaglandin inhibitors and atosiban are effective in prolonging pregnancy for 24,48 hours. Of these three agents, atosiban has the best safety profile. There are no placebo-controlled studies with calcium channel blockers or nitric oxide donors. However, because of their ease of use and efficacy compared with the ,-agonists, calcium channel blockers are widely used. Calcium channel blockers appear to have a better safety profile than the ,-agonists, but there are still significant cardiovascular side effects associated with their use. Indomethacin, although proven to be efficacious, has a safety profile that limits its utility for other than short courses. Magnesium sulphate is the most commonly used tocolytic in the United States, despite a lack of evidence for its efficacy. Although magnesium sulphate appears to have a good safety profile, serious side effects have been reported with its use. The choice of tocolytics is commonly based on personal preference. Whichever tocolytic is chosen, the fundamental parturitional process is not reversed by contemporary treatment, rather a reduction in uterine response to a stimulant; thus, the expectations of tocolytic treatment need to be reconsidered. [source] Efficacy of nifedipine or lisinopril in the treatment of hypertension after renal transplantation: a double-blind randomised comparative trialCLINICAL TRANSPLANTATION, Issue 6 2001Karsten Midtvedt Calcium channel blockers and angiotensin converting enzyme-inhibitors are commonly used in the treatment of hypertensive renal transplant recipients. The purpose of this study was to investigate if the response rate to treatment differs with these drugs in this setting. A single centre, prospective, randomised, double-blinded, comparative study to address the efficacy of controlled release nifedipine or lisinopril in the treatment of hypertension (diastolic blood pressure ,95 mmHg) in cyclosporin (CsA)-treated renal transplant recipients was performed. Recipients were randomised to receive either lisinopril (10 mg once daily) or controlled release nifedipine (30 mg once daily). The dose was doubled on indication. The number of responders (diastolic blood pressure <90 mmHg on monotherapy) were addressed during the early post-transplant phase (first 3 months) and during a late post-transplant phase (from 3 to 12 months after renal transplantation) in the same patient population. One hundred and fifty-four patients (nifedipine=78, lisinopril=76) with untreated hypertension (diastolic blood pressure,95 mmHg) were randomised within 3 wk after renal transplantation. One hundred and twenty-tree patients (nifedipine=69, lisinopril=54) completed the study. Fourteen (20%) nifedipine-treated recipients responded during the early, and 26 (38%) during the late post-operative phase (months 4,12 after renal transplantation). Eleven (20%) lisinopril-treated recipients responded during the early, and 18 (33%) during the late post-transplant phase. Non-responders were, on average, 8.5±1.5 kg heavier both in the early phase and after 1 yr of treatment (p<0.01), and 6.1±0.9 yr older than responders (p<0.05). In conclusion, these results indicate that both controlled release nifedipine and lisinopril are equally efficient in the treatment of post-transplant hypertension. As monotherapy, both drugs show a ,response rate' of 20,38%, depending on time interval after transplantation. [source] Treatment of diabetic hypertensionDIABETES OBESITY & METABOLISM, Issue 5 2009David S. H. Bell Insulin resistance and hyperglycaemia combine to make hypertension more prevalent in the type 2 diabetic patient. Blood pressure goals below those for the non-diabetic subject have been shown to be more effective in lowering mortality and cardiovascular events in the diabetic patient. To achieve these goals in most cases, three to five antihypertensives from different therapeutic groups need to be utilized. Suppression of the renin,angiotensin system (RAS) with angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers or a renin inhibitor should be the primary therapy. A second goal should be suppression of the sympathetic nervous system utilizing a beta-blocker that does not increase insulin resistance. The addition of a diuretic, calcium channel blocker or a vasodilator to suppressors of the RAS and sympathetic nervous system aid in achieving hypertensive goals in the diabetic patient. Achieving hypertensive goals with suppression of the RAS and sympathetic nervous system should result in a decrease in mortality and cardiovascular events in the diabetic hypertensive patient. In this review article, the benefits and disadvantages of the different antihypertensive therapies in the diabetic patient are discussed. [source] CPU-86017 improves the compromised blood,brain barrier permeability mediated by impaired endothelial no system and oxidative stress caused by L -thyroxineDRUG DEVELOPMENT RESEARCH, Issue 3 2005Rong-Hui Du Abstract Impaired endothelial cell (EC) function leads to alterations in the permeability of the blood,brain barrier (BBB). There are two aspects of the transport through the BBB: from the blood to the brain (influx) and from the brain to the blood (efflux). An impaired EC model induced by L -thyroxine that compromises the influx and efflux properties of the BBB was used to assess responses to the intervention of CPU-86017 (an antioxidant and calcium channel blocker) and propranolol. CPU-86017 (t1/2=1.5 h) was also used as a target drug, leaving no traces in the brain and blood 24 h after administration. The permeability of the BBB was evaluated by using CPU-86017 after iv and icv injection and concentrations in the blood and brain being measured by high-performance liquid chromatography. The bidirectional permeability of CPU-86017 was impaired and associated with a reduced NO bioavailability assessed functionally by the vasoactivity in the model. Partial relief of NO bioavailability and oxidative stress induced by propranolol was consistent with a recovery of BBB efflux alone. Complete recovery in the efflux and influx of the BBB by CPU-86017 was a result of the complete restoration of NO bioavailability and reduction in oxidative stress. Normal BBB influx is dependent on an intact endothelial NO system, and efflux could be restored easily by partial improvement of NO bioavailability. CPU-86017 is thus more effective than propranolol in protecting the endothelium from damage produced by L -thyroxine through oxidative stress. Drug Dev. Res. 64:145,156, 2005. © 2005 Wiley-Liss, Inc. [source] AMPA receptor-mediated presynaptic inhibition at cerebellar GABAergic synapses: a characterization of molecular mechanismsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2004Shin'Ichiro Satake Abstract A major subtype of glutamate receptors, AMPA receptors (AMPARs), are generally thought to mediate excitation at mammalian central synapses via the ionotropic action of ligand-gated channel opening. It has recently emerged, however, that synaptic activation of AMPARs by glutamate released from the climbing fibre input elicits not only postsynaptic excitation but also presynaptic inhibition of GABAergic transmission onto Purkinje cells in the cerebellar cortex. Although presynaptic inhibition is critical for information processing at central synapses, the molecular mechanisms by which AMPARs take part in such actions are not known. This study therefore aimed at further examining the properties of AMPAR-mediated presynaptic inhibition at GABAergic synapses in the rat cerebellum. Our data provide evidence that the climbing fibre-induced inhibition of GABA release from interneurons depends on AMPAR-mediated activation of GTP-binding proteins coupled with down-regulation of presynaptic voltage-dependent Ca2+ channels. A Gi/o -protein inhibitor, N-ethylmaleimide, selectively abolished the AMPAR-mediated presynaptic inhibition at cerebellar GABAergic synapses but did not affect AMPAR-mediated excitatory actions on Purkinje cells. Furthermore, both Gi/o -coupled receptor agonists, baclofen and DCG-IV, and the P/Q-type calcium channel blocker ,-agatoxin IVA markedly occluded the AMPAR-mediated inhibition of GABAergic transmission. Conversely, AMPAR activation inhibited action potential-triggered Ca2+ influx into individual axonal boutons of cerebellar GABAergic interneurons. By suppressing the inhibitory inputs to Purkinje cells, the AMPAR-mediated presynaptic inhibition could thus provide a feed-forward mechanism for the information flow from the cerebellar cortex. [source] Anorexia nervosa and Raynaud's phenomenon: A case reportINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 8 2007Basak Yucel MD Abstract Objective: To describe and discuss potential relationships between anorexia nervosa (AN) and Raynaud's phenomenon, the course and concurrent treatment of these two disorders as they appeared simultaneously, and a potential treatment modification entailed in such concurrent therapies. Background: Although Raynaud's phenomenon has been described during the course of AN, the associations and interactions between these two conditions are not clear. Method: We report the medical workup, treatment, and outcomes in a 19-year old female patient who developed Raynaud's phenomenon following the onset of AN. Results: After treatment with nutritional rehabilitation, counseling, and individual and group therapy, the patient's weight, eating disorder-related behaviors, and attitudes improved significantly. Raynaud's related symptoms improved, following treatment with a calcium channel blocker and antiaggregant therapy. In conjunction with nutritional efforts to treat the patient's long-standing amenorrhea and osteopenia, the treatment team elected to also administer estrogen hormone in addition to oral calcium and vitamin D supplementation. Since oral contraceptives are to be avoided in patients with Raynaud's phenomenon who show clinical findings suggesting connective tissue disorder, the treatment team elected to treat this patient with transdermal hormone replacement therapy. Conclusion: The co-occurrence of AN and Raynaud's phenomenon merits close and persistent follow-up by a multidisciplinary team and may lead to alterations of usual therapeutic approaches. © 2007 by Wiley Periodicals, Inc. [source] Update on the Management of Hypertension: Recent Clinical Trials and the JNC 7JOURNAL OF CLINICAL HYPERTENSION, Issue 2004Marvin Moser MD Editor in Chief The following issues are highlighted: Emphasis is placed on the importance of systolic blood pressure elevations in estimating risk and in determining prognosis. A review of placebo-controlled clinical trials indicates that cardiovascular events are statistically significantly reduced with diuretic- or , blocker-based treatment regimens. The question of whether blood pressure lowering alone or specific medications make the difference in outcome is discussed. Based on the results of numerous trials, it is apparent that blood pressure lowering itself is probably of greater importance in reducing cardiovascular events than the specific medication used. Meta-analyses suggest, however, that the use of an agent that blocks the renin-angiotensin aldosterone system is probably more effective in diabetics and in patients with nephropathy than a regimen based on calcium channel blocker therapy. The Antihypertensive and Lipid-Lowering treatment to Prevent Heart Attack Trial (ALLHAT) reported no overall difference in coronary heart disease outcome among patients treated with a diuretic-based compared to a calcium channel blocker- or an angiotensin-converting enzyme inhibitor-based treatment program. However, patients in the diuretic group experienced fewer episodes of heart failure than in the calcium channel blocker group and fewer episodes of heart failure and strokes than those in the angiotensin-converting enzyme inhibitor group. Results were similar in diabetics and nondiabetics. Possible reasons for this outcome are discussed. The Australian National Blood Pressure 2 study, which was unblinded, reported a marginally significantly better outcome only in male patients receiving an angiotensin-converting enzyme inhibitor-based regimen compared to those receiving a diuretic-based program. Finally, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is reviewed. Highlights of this report include the new designation of prehypertension, i.e., blood pressures of 120,139 mm Hg/80,89 mm Hg. The JNC 7 suggested that diuretics should be the first-step drug of choice in most patients, but listed numerous specific reasons why other agents should be used in special situations. The report stressed that the majority of patients will require two or more medications to achieve goal blood pressure. [source] Vasorelaxant effect of Valeriana edulis ssp. procera (Valerianaceae) and its mode of action as calcium channel blockerJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2010Samuel Estrada-Soto Abstract Objectives, The aim was to evaluate the relaxant effect of extracts from Valeriana edulis and determine the possible mechanism of action of the hexanic extract as vasorelaxant agent. Methods, Extracts from rhizomes obtained by maceration (hexanic (HEVe), dichloromethanic (DEVe), methanolic (MEVe) and hydroalcoholic (HAEVe) (3.03,500 µg/ml)) were evaluated on aortic rat rings with and without endothelium. Key findings, Extracts induced a significant concentration-dependent and endothelium-independent relaxation on isolated rat aorta pre-contracted with noradrenaline (0.1 µm). HEVe, the most potent extract (0.15,50 µg/ml), induced relaxation in aortic rings pre-contracted with KCl (80 mm), with an IC50 value of 34.61 ± 1.41 µg/ml and Emax value of 85.0 ± 4.38%. Pretreatment with HEVe (30 µg/ml) also inhibited contractile responses to noradrenaline and CaCl2. HEVe (9.98 ± 2.0 µg/ml) reduced noradrenaline-induced transient contraction in Ca2+ -free solution, and inhibited contraction induced by KCl (80 mm). In endothelium-denuded rings, the vasorelaxant effect of HEVe was not modified by 1- H -[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (1 µm), tetraethylammonium (5 mm), glibenclamide (10 µm) or 2-aminopyridine (100 µm). Conclusions, Our results suggest that HEVe induces relaxation through an endothelium-independent pathway, involving blockade of Ca2+ channels, and this effect could be related to the presence of valepotriates. [source] Nifedipine enhances cGMP production through the activation of soluble guanylyl cyclase in rat ventricular papillary muscleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2005Kazuhiko Seya It is known that nifedipine, an L-type calcium channel blocker, increases cGMP production, which partially contributes to the relaxation of vascular smooth muscle. The aim of our investigation was to clarify whether or not nifedipine regulates cGMP production, which has a physiological role in cardiac muscle. To measure contractile responses and tissue cGMP levels, left ventricular papillary muscles prepared from male Wistar rats (350,400 g) were mounted in the isolated organ chamber under isometric conditions and electrically paced by means of platinum punctate electrodes (1 Hz, 1 ms duration). In papillary muscle preparation, the negative inotropic effect induced by nifedipine (30 to 300 nm) was significantly inhibited in the presence of ODQ (1H-[1,2,4]oxidazolo[4,3-a]quinoxaline-1-one; 10 ,m), a soluble guanylyl cyclase inhibitor. Furthermore, nifedipine (100 nm) strongly increased the tissue cGMP level, which was significantly decreased in the presence of ODQ. On the other hand, NG -monomethyl-l-arginine (100 ,m), a nitric oxide synthase inhibitor, did not inhibit either the negative inotropic effect or cGMP production induced by nifedipine. These results indicate that in rat left ventricular papillary muscle, nifedipine augments its negative inotropic effect at least partly through direct activation of cardiac soluble guanylyl cyclase but not nitric oxide synthase. [source] Protective effects of steroids from Allium chinense against H2O2 -induced oxidative stress in rat cardiac H9C2 cellsPHYTOTHERAPY RESEARCH, Issue 3 2010Gang Ren Abstract Allium chinense, a traditional herbal medicine, has been used for the treatment of cardiovascular diseases for hundreds of years. In this study, A. chinense steroids (ACSs) including three steroidal glycosides and their parent aglycones were isolated from the bulbs of A. chinense. For the first time, their cardioprotective effects were evaluated in cultured rat cardiac H9C2 cells by pretreatment with ACSs for 24,h before exposure to 0.2,mm H2O2. The results showed the cell viability decreased markedly when H9C2 cells were incubated with 0.2,mm H2O2 alone for 2,h, while the cell lipid peroxidation (estimated by the excessive production of nitric oxide and malondialdehyde) and intracellular free calcium concentration ([Ca2+]i) increased significantly. The addition of 20,,m (below the toxic concentration) of ACSs notably attenuated the cellular injury induced by H2O2. The effects of ACSs in our experiments were similar to those of nimodipine, a clinically applied calcium channel blocker. Preliminary analysis of the structure,activity relationship indicated that ACSs with a spirostane-type skeleton exhibited stronger protection than that with a furostane-type skeleton, and glycosylation of the steroids could substantially lower the protective activities. The above results suggested the protective effects of steroids originated from A. chinense on the oxidative injury of H9C2 cells and ACSs may have potential for preventing cardiac injuries induced by oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd. [source] Periodontal healing and bone regeneration in response to azithromycinAUSTRALIAN DENTAL JOURNAL, Issue 2 2010R Hirsch Abstract Azithromycin, first synthesized in 1980, is a macrolide antibiotic related to erythromycin. It is widely used by the medical profession as a broad-spectrum antibiotic in the treatment of pneumonia, urinary tract infections and tonsillitis. In addition to its antibiotic properties, azithromycin has immune-modulating effects and is used for this reason in the management of cystic fibrosis and chronic obstructive pulmonary diseases. The drug is taken up by neutrophils, macrophages and fibroblasts, and is slowly released by these cells. Three diverse case reports are presented in which a single course of azithromycin (consisting of one 500 mg tablet being taken a day for three days) was prescribed before any periodontal intervention occurred. Azithromycin was the principal mode of treatment of severe chronic and aggressive periodontitis in Cases 1 and 2. Azithromycin, together with monthly subgingival debridement, was the treatment in Case 3 (severe chronic periodontitis in a poorly controlled diabetic complicated by gingival overgrowth related to medication with a calcium channel blocker). Favourable resolution of inflammation, reduction in pocket depths and evidence of bone regeneration were evident, even when no periodontal treatment had occurred. In Case 3, resolution of gingival overgrowth occurred over eight months. The potential implications for periodontal management, understanding of the pathogenesis of periodontal diseases and periodontal research are briefly discussed. [source] Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanismsBIPOLAR DISORDERS, Issue 8 2008Alan G Mallinger Objectives:, Attenuation of protein kinase C (PKC) is a mechanism common to both established (lithium, valproate) and some novel (tamoxifen) antimanic agents. Verapamil, although primarily known as a calcium channel blocker, also has PKC inhibitory activity. Verapamil has shown antimanic activity in some but not all studies. Therefore, we investigated verapamil, used alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. Methods:, Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n = 45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n = 10) or continued-lithium (n = 8). Phase 2 nonresponders (n = 10) were assigned to combined verapamil/lithium in Phase 3. Results:, Response in Phase 2 did not differ significantly between verapamil and continued-lithium. During Phase 3, response to combined treatment was significantly better than overall response to monotherapy in Phase 2 (Fisher's Exact test, p = 0.043). Mania ratings improved during combined treatment in Phase 3 by 88.2% (linear mixed model analysis, F = 4.34, p = 0.013), compared with 10.5% improvement during Phase 2. Conclusions:, In this preliminary investigation, verapamil monotherapy did not demonstrate antimanic efficacy. By contrast, the combination of verapamil plus lithium was highly efficacious. Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium. This effect may be mediated by additive actions on PKC inhibition, which may be an important mechanism for antimanic agents in general. [source] Superior palatability of crushed lercanidipine compared with amlodipine among childrenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2010Gregorio Milani WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Among children, medication palatability is crucial for adherence to therapeutic regimen. , Since there is a lack of appropriate formulations for children prescribed drugs originally designed for adults, parents crush available tablets and administer the medication mixed with solid food or a palatable drink. , Crushed amlodipine, a very popular calcium channel blocker, is bitter and unpalatable. WHAT THIS STUDY ADDS , From the perspective of the child with arterial hypertension, the taste of pulverized lercanidipine is superior to that of pulverized amlodipine. AIMS To compare the taste of equivalent doses of pulverized amlodipine and lercanidipine, two calcium channel blockers, among children with kidney disease. METHODS Each child received a test dose of 1 mg of amlodipine besylate and 2 mg of lercanidipine in a single-blinded fashion. Children indicated their preference by pointing to the appropriate face on a visual analogue scale (VAS) that depicts five degrees of pleasure. RESULTS The VAS palatability score assigned to lercanidipine was higher than that assigned to amlodipine both in nine children 4,7 years of age (P < 0.005) and in 10 children 8,11 years of age (P < 0.005). The preference for lercanidipine was statistically significant in both girls (P < 0.02) and boys (P < 0.001) and in both children initially presented amlodipine (P < 0.005) and children initially presented lercanidipine (P < 0.005). CONCLUSIONS There is a lack of appropriate formulations for children prescribed drugs originally designed for adults, such as calcium channel blockers. Parents therefore crush available tablets and administer the medication mixed with solid food or a palatable drink. From the perspective of the child, the taste of pulverized lercanidipine is superior to that of pulverized amlodipine. [source] KMUP-1 activates BKCa channels in basilar artery myocytes via cyclic nucleotide-dependent protein kinasesBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2005Bin-Nan Wu This study investigated whether KMUP-1, a synthetic xanthine-based derivative, augments the delayed-rectifier potassium (KDR)- or large-conductance Ca2+ -activated potassium (BKCa) channel activity in rat basilar arteries through protein kinase-dependent and -independent mechanisms. Cerebral smooth muscle cells were enzymatically dissociated from rat basilar arteries. Conventional whole cell, perforated and inside-out patch-clamp electrophysiology was used to monitor K+ - and Ca2+ channel activities. KMUP-1 (1 ,M) had no effect on the KDR current but dramatically enhanced BKCa channel activity. This increased BKCa current activity was abolished by charybdotoxin (100 nM) and iberiotoxin (100 nM). Like KMUP-1, the membrane-permeable analogs of cGMP (8-Br-cGMP) and cAMP (8-Br-cAMP) enhanced the BKCa current. BKCa current activation by KMUP-1 was markedly inhibited by a soluble guanylate cyclase inhibitor (ODQ 10 ,M), an adenylate cyclase inhibitor (SQ 22536 10 ,M), competitive antagonists of cGMP and cAMP (Rp-cGMP, 100 ,M and Rp-cAMP, 100 ,M), and cGMP- and cAMP-dependent protein kinase inhibitors (KT5823, 300 nM and KT5720, 300 nM). Voltage-dependent L-type Ca2+ current was significantly suppressed by KMUP-1 (1 ,M), and nearly abolished by a calcium channel blocker (nifedipine, 1 ,M). In conclusion, KMUP-1 stimulates BKCa currents by enhancing the activity of cGMP-dependent protein kinase, and in part this is due to increasing cAMP-dependent protein kinase. Physiologically, this activation would result in the closure of voltage-dependent calcium channels and the relaxation of cerebral arteries. British Journal of Pharmacology (2005) 146, 862,871. doi:10.1038/sj.bjp.0706387 [source] Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Feng Gao Ischaemia/reperfusion causes intracellular calcium overloading in cardiac cells. Administration of calcium antagonists reduces myocardial infarct size. Recent in vitro studies have demonstrated that calcium plays a critical role in the signal transduction pathway leading to apoptosis. However, whether or not calcium antagonists may reduce myocardial apoptosis induced by ischaemia-reperfusion, and thus decrease myocardial infarction, has not been directly investigated. The present study investigated the effects of benidipine, an L-type calcium channel blocker, on myocardial infarct size, apoptosis, necrosis and cardiac functional recovery in rabbits subjected to myocardial ischaemia/reperfusion (MI/R, 45 min/240 min). Ten minutes prior to coronary occlusion, rabbits were treated with vehicle or benidipine (10 ,g kg,1 or 3 ,g kg,1, i.v.). In the vehicle-treated group, MI/R caused cardiomyocyte apoptosis as evidenced by DNA ladder formation and TUNEL positive nuclear staining (12.2±1.1%). Treatment with 10 ,g kg,1 benidipine lowered blood pressure, decreased myocardial apoptosis (6.2±0.8%, P<0.01 vs vehicle) and necrosis, reduced infarct size (20±2.3% vs 49±2.6%, P<0.01), and improved cardiac functional recovery after reperfusion. Administering benidipine at 3 ,g kg,1, a dose at which no haemodynamic effect was observed, also exerted significant anti-apoptosis effects, which were not significantly different from those observed with higher dose benidipine treatment. However, treatment with this low dose benidipine failed to reduce myocardial necrosis. These results demonstrate that benidipine, a calcium antagonist, exerts significant anti-apoptosis effects, which are independent of haemodynamic changes. Administration of benidipine at a higher dose produced favourable haemodynamic effects and provided additional protection against myocardial necrotic injury and further improved cardiac functional recovery. British Journal of Pharmacology (2001) 132, 869,878; doi:10.1038/sj.bjp.0703881 [source] Verapamil Toxicity Dysregulates the Phosphatidylinositol 3-Kinase PathwayACADEMIC EMERGENCY MEDICINE, Issue 4 2008Laura K. Bechtel PhD Abstract Objectives:, Recent animal research and clinical case reports suggest benefit from high-dose insulin therapy (HDIT) for the treatment of calcium channel blocker (CCB) toxicity. One molecular signaling pathway, the phosphatidylinositol 3-kinase (PI3K) pathway, that contributes to CCB toxicity and the efficacy of HDIT, was examined for a role in this phenomenon. Methods:, A differentiated 3T3-L1 adipocyte model system was utilized to characterize metabolic and molecular signaling events dysregulated in response to acute CCB toxicity. Glucose uptake assays were performed in the presence of representatives of three classes of CCB drugs, and the ability of HDIT to reverse observed inhibition was assessed. Western blot analyses were utilized to probe which insulin-dependent signaling pathway was inhibited by CCB toxicity. Results:, Representative compounds from the dihydropyridine and phenylalkylamine classes of CCBs were more effective at inhibiting glucose uptake in differentiated 3T3-L1 adipocytes than a representative from the benzothiazepine class. Phosphorylation at serine 473 of the Akt protein (P-Akt), a protein representing a common pathway for insulin receptors (IR), insulinlike growth factor receptors (IGFR), and hybrid receptors formed by IR and IGFR subunits, was abolished in the presence of toxic doses of the phenylalkylamine CCB verapamil. Phosphorylation at serine 473 of Akt was rescued in the presence high concentrations of insulin. Conclusions:, These data suggest that dysregulation of the insulin-dependent PI3K pathway is partially responsible for insulin resistance and the hyperglycemic state observed in response to acute CCB toxicity. [source] Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertensionDIABETES OBESITY & METABOLISM, Issue 5 2001M. H. Uehara SUMMARY Background Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. Patients and Methods A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. Results Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54 + 1.72 to 7.54 + 1.33 mmol/l, p <,0.05), although HbA1c had decreased in both groups (PG: 6.7±3.0 to 5.9±2.6%; MG: 5.3±1.5 to 4.6±0.9%; p <,0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7±8.0 to 99.2±9.3 mmHg, p <,0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0±62.4 to 38.0±23.0 pmol/l, p <,0.05) and the insulin resistance index (3.5±2.7 to 1.8±1.0, p <,0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8±7.9 to 21.4±14.6 ,g/l; MG: 18.5±10.3 to 18.4±8.9 ,g/l). Dopamine levels increased significantly only in metformin-treated subjects. Conclusions Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels. [source] Treatment of diabetic nephropathy in its early stagesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2003Giacomo Deferrari Abstract Diabetic nephropathy is one of the most frequent causes of end-stage renal disease (ESRD), and, in recent years, the number of diabetic patients entering renal replacement therapy has dramatically increased. The magnitude of the problem has led to numerous efforts to identify preventive and therapeutic strategies. In normoalbuminuric patients, optimal glycemic control (HbA1c lower than 7.5%) plays a fundamental role in the primary prevention of ESRD [weighted mean relative risk reduction (RRR) ,37% for metabolic control versus trivial renoprotection for intensive anti-hypertensive therapy or ACE-inhibitors (ACE-I)]. In the microalbuminuric stage, strict glycemic control probably reduces the incidence of overt nephropathy (weighted mean RRR ,50%), while blood pressure levels below 130/80 mmHg are recommended according to the average blood pressure levels obtained in various studies. In normotensive patients, ACE-I markedly reduce the development of overt nephropathy almost regardless of blood pressure levels; in hypertensive patients, ACE-I are less clearly active (weighted mean RRR ,23% versus other drugs), whereas angiotensin-receptor blockers (ARB) appear strikingly renoprotective. Once overt proteinuria appears, it is uncertain whether glycemic control affects the progression of nephropathy. In type 1 diabetes, various anti-hypertensive treatments, mainly ACE-I, are effective in slowing down the progression of nephropathy; in type 2 diabetes, two recent studies demonstrate that ARB are superior to conventional therapy or calcium channel blockers (CCB). In clinical practice, pharmacological tools are not always used to the best benefit of the patients. Therefore, clinicians and patients need to be educated regarding the renoprotection of drugs inhibiting the renin-angiotensin system (RAS) and the overwhelming importance of achieving target blood pressure. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pharmacogenetics of antihypertensive treatmentDRUG DEVELOPMENT RESEARCH, Issue 3 2004Donna K. Arnett Abstract Hypertension is a common disorder associated with increased cardiovascular morbidity and mortality. Unfortunately, in the United States, only about one third of those who are aware of their hypertensive status successfully control their blood pressure. One reason for this is the variable and unpredictable response individuals have to pharmacologic treatment. Clinicians often resort to a trial-and-error approach to match patients with effective drug treatment. It is the goal of hypertension pharmacogenetics to apply knowledge of genetic predictors of treatment response to drugs that lower blood pressure and to translate this knowledge into clinical practice. To date, more than 30 studies have investigated associations between specific genetic polymorphisms and response to particular antihypertensive drugs. Angiotensin-converting enzyme inhibitors have been most frequently studied, followed by diuretics, beta-blockers, angiotensin II blockers, adrenergic alpha-agonists, and calcium channel blockers. Renin,angiotensin,aldosterone system genes have been the most widely studied, with the angiotensin-converting enzyme I/D variant being typed in about one third of all hypertension pharmacogenetic studies to date. In a number of cases, significant and potentially promising associations between genes and drug treatments have been reported. However, taken in sum, the literature suggests that the path from gene-drug-outcome association studies to clinically useful knowledge may be neither short nor direct. In the future, carefully designed studies must acknowledge that hypertension is caused by multiple genes and environmental factors that act in concert. These considerations, along with a better understanding of the complexities of the biology of hypertension, open the next set of opportunities for hypertension pharmacogenetics research. Drug Dev. Res. 62:191,199, 2004. © 2004 Wiley-Liss, Inc. [source] Chalcones as potent antiplatelet agents and calcium channel blockersDRUG DEVELOPMENT RESEARCH, Issue 1 2001Chun-Nan Lin Abstract In an effort to continually develop potent antiplatelet agents with vasorelaxing and antiinflammatory actions, a novel series of antiinflammatory chalcones was continually screened to evaluate their antiplatelet and vasorelaxing effects. Their structure,activity relationships and mode of action were discussed and characterized. A novel series of antiinflammatory chalcones was studied on antiplatelet effect in rabbit washed platelets and human platelet-rich plasma (PRP) and vasorelaxing effect in rat thoracic aorta. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives and 13,15 also had a potent inhibitory effect on cyclooxygenase. The selective chalcones 12,16 tested in human PRP significantly inhibited secondary aggregation induced by adrenaline. In rat thoracic aorta, most of chalcones at high concentration significantly depressed the contractions induced by Ca2+ (1.9 mM) in high K+ (80 mM) medium and the phasic and tonic contractions caused by norepinephrine (3 ,M). In the rat thoracic aorta, the phenylephrine- and high K+ -induced 45Ca2+ influx were both inhibited by a selective chalcone derivative, 14. These results indicate that the antiplatelet actions of chalcones are mainly mediated through the suppression of cyclooxygenase activity and reduced thromboxane formation and their inhibitory effects on the contractile response caused by high K+ and norepinephrine in rat thoracic aorta are mainly due to inhibition of Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels. Drug Dev. Res. 53:9,14, 2001. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||