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 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.
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PMID:Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications. 332 59

Excessive accumulation of intracellular calcium in Duchenne muscular dystrophy (DMD) may be a necessary step in the process that causes muscle damage in this disease. Because of this possibility, a controlled trial of the calcium channel blocking agent nifedipine was undertaken. One hundred and five patients were randomized and treated in a double-blind manner for 18 months. Muscle strength, contractures, functional ability, cardiopulmonary changes, and laboratory data were monitored. The dose of nifedipine was 0.75-1 mg/kg/day in the first 6 months and 1.5-2 mg/kg/day for the next 12 months. Satisfactory blood levels of nifedipine were attained. The study had a power greater than 0.99 to detect a slowing of the illness to 25% of its original rate of progression. No significant improvement was demonstrated in the treated group. One or more of the frequent mild side effects of flushing, dizziness, and leg edema, often associated with the use of nifedipine in adults, occurred transiently in approximately one-half of the patients in the nifedipine group and in 21% of the placebo group. Four patients died, two on nifedipine and two on placebo. This study demonstrates that nifedipine is safe to administer in children, but that it is without beneficial effect on the course of DMD.
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PMID:Clinical investigation in Duchenne dystrophy. VI. Double-blind controlled trial of nifedipine. 355 Apr 55

Ten hypertensive patients with poor responses to standard antihypertensive therapy were treated with the calcium channel antagonist nifedipine in an attempt to obtain better BP control. The drug was highly effective in significantly lowering BP immediately (average decrease, 58/29 mm Hg) and after three to eight weeks of maintenance therapy (average decrease, 49/27 mm Hg), with no significant change in heart rate observed at either time. No adverse interactions between nifedipine and other concurrent medications, including digoxin and beta-adrenergic blockers, were noted. Drug-related side effects of tachycardia or flushing necessitated the withdrawal of nifedipine therapy in two patients. We conclude that nifedipine may be safely employed in an outpatient setting as a useful adjunct to current antihypertensive drug regimens.
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PMID:Use of nifedipine as an adjunct to current antihypertensive therapy. 614 43

Nitrendipine (BAY e 5009) is a new calcium channel blocker with a marked effect on excitation-contraction coupling in different types of muscle cells. It has many similarities to the established agent, nifedipine. In the present study, nitrendipine was evaluated in a double-blind within-patient comparison. Twelve patients with essential hypertension were given nitrendipine 20 mg or 40 mg orally for three weeks following a 1-week placebo period. After a second 1-week placebo period, there was a crossover to the alternative dosage (20 or 40 mg respectively), and active therapy was again given for 3 weeks. Both doses of nitrendipine caused a significant and equal reduction of arterial pressure, which persisted for at least 24 hours. Only the highest dose caused an increase in heart rate. There were a few reports of headaches, flushing, and palpitation, particularly after the 40 mg dose. There was a significant correlation between the reduction of mean arterial pressure and the log plasma concentration (20 mg: r = -0.88, p less than 0.01; 40 mg: r = -0.94, p less than 0.001). There was a linear relationship between the area under the curve and the oral dose, indicating that liver enzyme saturation had not occurred. There was no accumulation of nitrendipine in plasma during 3 weeks of treatment.
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PMID:Pharmacokinetic and pharmacodynamic parameters in patients treated with nitrendipine. 634 73

Lacidipine is an orally administered calcium channel blocker of the dihydropyridine class, which shows selectivity for vascular smooth muscle over cardiac tissue and has a long duration of action. In studies using ambulatory blood pressure monitoring, lacidipine 2 to 8mg administered once daily in the morning reduced blood pressure over 24 hours, with the reductions being greater during the day than at night in some studies. 77 to 87% of patients with mild to moderate hypertension had their blood pressure controlled by treatment with lacidipine 2 to 8 mg/day for 1 to 4 months in dose-finding studies. When administered once daily, lacidipine 4 to 6 mg was equivalent in antihypertensive efficacy to hydrochlorothiazide 25 to 50 mg/day, atenolol 50 to 100 mg/day, and the prototype calcium channel blocker nifedipine 20 to 40 mg twice daily (sustained-release formulation). The adverse effects of lacidipine are those common to other dihydropyridine calcium channel blockers, and include headache, flushing, ankle oedema, dizziness and palpitations. The long term effects of lacidipine on cardiovascular morbidity and mortality, and possible additional clinical benefits in terms of its antiatherosclerotic effects, are under investigation; the outcome of these studies will be important in defining the future role of this agent in the treatment of hypertension. Thus, available evidence suggests lacidipine provides a further alternative to the dihydropyridine calcium channel blockers currently available for the treatment of essential hypertension.
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PMID:Lacidipine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of hypertension. 752 28

Nicardipine is a second generation dihydropyridine calcium antagonist which selectively inhibits vascular smooth muscle contraction. In elderly patients, the drug has demonstrated clinical efficacy in the management of hypertension, angina pectoris and ischaemia-related cerebrovascular disease. In particular, nicardipine effectively controls blood pressure in elderly hypertensive patients with or without coexistent disease. In noncomparative trials, a regimen containing nicardipine has been associated with an improvement of symptoms in hypertensive patients with concurrent coronary artery, cerebrovascular or peripheral vascular disease, while in essentially 'healthy' elderly hypertensive patients, nicardipine monotherapy has resulted in improved indices of mobility and cognitive function. As yet, however, there is no evidence that nicardipine (and/or other calcium channel antagonists) decreases cardiovascular morbidity and mortality in elderly patients, as has been demonstrated for more established antihypertensive therapies, namely diuretics and/or beta-blockers. The pharmacokinetic properties of nicardipine in elderly hypertensive patients appear to be similar to those in younger patients. The main adverse events associated with nicardipine in the elderly are related to the vasodilator properties of the drug and include pedal oedema, headache and flushing. However, the drug does not exacerbate spontaneous postural hypotension in the elderly, nor does it adversely affect the coronary artery disease risk profile, even in patients with type II diabetes mellitus. In summary, widespread clinical experience in the elderly indicates that nicardipine monotherapy or a regimen containing nicardipine is useful for the treatment of hypertension, particularly in patients with coexistent coronary artery, cerebrovascular or peripheral vascular disease. Nicardipine monotherapy has also demonstrated efficacy in angina pectoris and shown promise in the management of ischaemia-related cerebrovascular diseases, notably subarachnoid haemorrhage.
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PMID:Nicardipine. A review of its pharmacology and therapeutic efficacy in older patients. 847 49

Amlodipine belongs to the dihydropyridine class of calcium channel blockers. Both short and long term studies indicate that amlodipine effectively lowers mild to moderately elevated blood pressure and relieves symptoms of angina pectoris. In comparative studies, its antihypertensive efficacy is similar to that of other established agents such as beta-blockers, diuretics, ACE inhibitors and other calcium channel blockers (including the dihydropyridines); limited comparative data are, however, available in patients with angina pectoris. Amlodipine may offer potential in patients with congestive heart failure. Vasodilator adverse events such as oedema, headaches, and flushing are commonly observed with amlodipine. The drug does not appear to cause postural hypotension, reflex tachycardia or cardiac conduction disturbances. Comparative studies suggest that amlodipine is at least as well tolerated as other standard agents. Thus, amlodipine provides an attractive therapeutic option for the treatment of hypertension, and offers potential for patients with angina pectoris. Its beneficial effects in patients with congestive heart failure require confirmation in future studies.
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PMID:Amlodipine. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease. 852 73

In rat models of liver preservation, the primary event leading to liver graft failure after cold storage is a reperfusion injury causing damage to sinusoidal endothelial cells and activation of Kupffer cells (KC). After storage for longer than 16 h in University of Wisconsin solution, reperfusion induces rapid endothelial cell killing. Kupffer cell activation also occurs as indicated by cell surface ruffling, degranulation, release of hydrolytic enzymes, generation of oxygen radicals, and increased phagocytosis. Down-regulation of KC activity with nisoldipine or pentoxifylline improves graft survival. Moreover, pretreatment of donors with small amounts of endotoxin to activate KC causes a drastic reduction of graft survival. Together, KC activation and endothelial damage cause marked microcirculatory disturbances after transplantation characterized by reduced and uneven blood flow and increased leucocyte and platelet adhesion. Such events culminate in inflammation, necrosis and fulminant graft failure. Modification of reperfusion conditions can reduce the extent of injury. In particular, flushing livers with Carolina rinse solution (CRS) at the end of storage reduces endothelial cell killing, suppresses KC activation, improves the microcirculation, and increases graft survival. Active ingredients in CRS include antioxidants (allopurinol, desferrioxamine and glutathione), adenosine and slightly acidic pH (6.5). Other potentially important ingredients are nicardipine, a calcium channel blocker, and fructose, glucose and insulin to promote glycolysis. The cytoprotective amino acid, glycine, further improves the performance of Carolina rinse solution. Reperfusion-induced changes to nonparenchymal cells play an essential role in damage to livers preserved for transplantation surgery. Understanding the role of sinusoidal endothelial cells and KC in this injury has led to promising new strategies to prolong organ storage and reduce graft failure.
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PMID:Dual role of Kupffer cell activation and endothelial cell damage in reperfusion injury to livers stored for transplantation surgery. 858 53

Primary Raynaud's phenomenon is common, particularly in younger women, and may be familial. Vasospasm is not confined to the digits and may involve, for example, the tongue and nose, and also visceral organs like the heart, oesophagus or lung and cerebral circulation. Symptoms tend to be milder in primary compared with secondary Raynaud's phenomenon, which is associated with other disorders such as the connective tissue diseases. Indeed, the severity of symptoms often acts as the predictor for the much later onset of the associated systemic disease. Occupational Raynaud's phenomenon is related to the use of vibrating instruments, and a significant proportion of patients may be cured by an early change in job. In those over 60 years of age, Raynaud's phenomenon is commonly a result of atherosclerotic obstructive arterial disease, and screening for and treatment of the risk factors is appropriate. The best-studied mechanisms in Raynaud's phenomenon involve the blood and vascular endothelium. Microcirculatory flow may be impeded by activated platelet clumps, rigid red and white blood cells and damaged endothelium. These platelet clumps, white blood cells and damaged endothelium also release vasoactive/vasoconstrictive compounds which may additionally trigger the clotting cascade and thrombosis. Initial management for mild disease should focus on support and advice regarding avoidance of known precipitating factors, including vasospastic drugs. Cold protection with warming agents, 'Abel' shoes and also electrically heated gloves and socks is effective, but may be too cumbersome and inconvenient for some patients. Simple vasodilators like naftidrofuryl, inositol nicotinate and possibly pentoxifylline (oxpentifylline) are useful in mild disease, with adverse effects like headache and flushing being less problematic. The 'gold standard' of Raynaud's phenomenon treatment is nifedipine, a calcium channel antagonist/blocker. Full dosage, however, can be limited by ankle swelling, headache and flushing, but adverse effects may be reduced by using the 'retard' or long-acting preparations. Adverse effects are also reduced with the newer calcium channel antagonists like diltiazem but at the expense of efficacy. Useful, enhanced benefit is also achieved by combination therapy with vasodilators. Newer treatments include the prostaglandin analogues which are effective but disadvantaged by their parenteral route of administration, and lack of licence in some countries. Oral preparations are, however, being studied and are in the pipeline. Essential fatty acid supplementation is mildly effective, while ketanserin and calcitonin gene-related peptide both look promising. Lumbar sympathectomy retains its important role in the treatment of Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic relief is now possible for many patients with Raynaud's phenomenon and this should certainly be the aim for all patients seeking medical help.
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PMID:Pharmacotherapy of Raynaud's phenomenon. 911 18

During the past 20 years the number of subclasses of calcium channel blockers has increased from one to four. Three classes have only a single clinically approved compound: verapamil, diltiazem, and mibefradil. The fourth class, dihydropyridines, contains numerous compounds. All agents are effective in lowering blood pressure in short-term studies, and side effects that trouble the patient are infrequent. Long-term studies in hypertensive patients are limited. Short-acting agents such as nifedipine have been associated with an increased cardiovascular risk in some, but not all studies. These agents also probably create a compliance problem for hypertensive patients because of the need for multiple daily doses and their unpleasant side effects, e.g., ankle edema, palpitations, and flushing. Therefore, they are not useful or indicated for the treatment of hypertensive patients. No data have suggested that long-acting dihydropyridines or nondihydropyridine calcium channel blockers share the same fate. Indeed, several lines of evidence suggest the opposite: they have a cardioprotective effect. However, definitive information will require the completion of several long-term trials, including ALLHAT, CONVINCE, HOT, INSIGHT and NORDIL. Finally, it is important to reflect on the lessons learned from the controversy associated with the potential risks of calcium channel blockers. First, disagreements are common when one uses case-controlled studies and are reflective of the poor precision of the methods used. What is statistically relevant in one study may not hold true for another and may have no clinical relevance, particularly if the relative risk is less than 2. Investigators need to temper their enthusiasm to reflect this reality. Second, at the cutting edge of science there is probably relatively little agreement about what is correct among equally competent scientists. All have bias in their positions and should both recognize and admit so to themselves and their colleagues. Inferring that those who disagree have an unstated secondary agenda that will bring personal financial rewards or government accolades is inappropriate and counterproductive. Third, the randomized clinical trial, despite all its imperfections, is still the best tool to establish common ground on controversial issues. Finally, what may seem best from the public health perspective may not be in the best interest of the individual patient--a possibility that physicians have to constantly consider. For example, no public health benefit occurs if patients remain hypertensive because they fail to take their medications, no matter what the medication.
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PMID:Use of calcium channel blockers in hypertension. 950 92


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