Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although calcium antagonists form a mainstay of therapy in patients with angina pectoris, the currently available agents have significant limitations. Nifedipine, diltiazem, and verapamil are all high-clearance agents with significant hepatic extraction and rapid clearance, leading to limited and short-lived bioavailability necessitating frequent daily administration. In contrast, amlodipine, a dihydropyridine calcium antagonist, has a long half-life of 35-50 h (compared with 3 to 4 h elimination half-life of diltiazem, verapamil, and nifedipine). After oral doses, the relative bioavailability of amlodipine is high (64%) and absorption is smooth, with peak plasma levels being achieved 6-12 h postdose. Bioavailability is not affected by the consumption of food. In common with other dihydropyridine calcium antagonists, amlodipine is eliminated mainly by metabolism. None of the metabolites of amlodipine has significant calcium antagonist effects in humans. In contrast to verapamil or diltiazem, amlodipine has no effect on sinus or atrioventricular node and little or no effect on the resting heart rate. Amlodipine does not have any appreciable negative inotropic effect with the relevant clinical dose. Other clinical studies have shown amlodipine to be effective when used once-daily in chronic stable angina and vasospastic angina. Comparative studies indicate that the antianginal efficacy of amlodipine is comparable to the beta blocker nadolol and the benzothiazepine calcium antagonist diltiazem. Amlodipine has also been found to provide improved antianginal effects when combined to treatment with beta blockers and/or long-acting nitrates. Treatment with amlodipine either as monotherapy or combined with other antianginal therapy for up to 26 weeks shows that efficacy is maintained, with no evidence of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Amlodipine once a day in stable angina: double-blind crossover comparison with placebo. 837 Jan 91

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.
 ...
PMID:Amlodipine. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease. 852 73

Calcium channel blockers are active in variant angina principally by preventing coronary vasospasm. However, a direct antiischemic effect may also occur. In open-chest dogs, an attack of variant angina was mimicked by a 2-min critical coronary stenosis, and the following reversible myocardial ischemia was assessed by measuring the decrease of segmental shortening. We compared the antiischemic mechanism of mibefradil, a T and L calcium channel blocker, with that of amlodipine, a pure L channel blocker. Both drugs showed a similar relationship between the decrease of the rate-pressure product and the antiischemic effect, but only mibefradil reduced heart rate. Amlodipine and mibefradil at the highest doses tested (20 and 70 micrograms/kg/min, respectively) restored 68 +/- 8 and 76 +/- 5% of segmental shortening in the ischemic area, respectively, as compared with preischemic values. Matching blood pressure (by intraaortic balloon) or heart rate (by atrial pacing) to predrug values showed that the antiischemic effect was mainly afterload-dependent for amlodipine and heart rate-dependent for mibefradil. We conclude that in variant angina, in addition to their antivasospastic effects, calcium channel blockers may be antiischemic by a direct myocardial effect associated with a decrease of the rate pressure product. Blockade of the T channel does not seem to participate in the direct antiischemic effect of mibefradil but could explain the decrease of heart rate.
 ...
PMID:Mechanism of the antiischemic effect of mibefradil, a selective T calcium channel blocker in dogs: comparison with amlodipine. 865 47

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
 ...
PMID:What, if anything, is controversial about calcium antagonists? 896 30

Depending upon the definition used, restenosis occurs in 10-60% of patients who undergo percutaneous transluminal coronary angioplasty. Restenosis appears to be the result of a combination of pathophysiological processes, including elastic recoil of arterial walls, platelet deposition and thrombus formation and resultant fibro-cellular neointimal hyperplasia. A range of pharmacological interventions has been used in an attempt to reduce the rate of restenosis following angioplasty, with little success. Furthermore, many patients who undergo angioplasty still suffer from ischaemia after the procedure. Calcium antagonists, such as the long-acting dihydropyridine amlodipine, have been demonstrated to be effective in the control of both symptomatic and asymptomatic ischaemia and are, therefore, likely to be of utility for this purpose in angioplasty patients. Calcium antagonists also exhibit characteristics that may lead to a reduction in restenosis, in that they inhibit platelet aggregation, reduce vasoplasm and inhibit the action of mitogens which stimulate proliferation and migration of smooth muscle cells. The results of five trials of calcium antagonists in angioplasty patients have been individually unconvincing in terms of prevention of restenosis, only one trial demonstrated a significant effect. However, a meta-analysis of these results has demonstrated an approximately 30% reduction in the chance of restenosis in those patients treated with calcium antagonists. The Coronary Angioplasty Amlodipine in Restenosis (CAPARES) trial has been initiated to assess the impact of amlodipine upon the rate of restenosis and angina/ischaemia after the procedure.
 ...
PMID:Clinical promise of calcium antagonists in the angioplasty patient. 915 66

An interim analysis of patient compliance is reported in 234 hypertension outpatients who were entered into a large-scale, open, crossover, comparative study between a new-generation calcium antagonist, amlodipine (5 mg, once daily), and nifedipine SR (20 mg, twice daily). An analysis was also performed on 84 outpatients with stable angina pectoris, who were included in an open, parallel study and received the same dosing regimen of either amlodipine or nifedipine SR as the patients in the hypertension arm of the study. In the hypertensive patients, there were significant differences in favor of amlodipine, using all four methods to assess patient compliance. In the angina patients, a significant difference between the groups in favor of amlodipine was only found using the "correct dosing" and the "timing compliance" methods. With the traditional pill-counting and also the "taking compliance" methods, there was no observed difference in compliance between the two groups. It was concluded that, in terms of patient compliance, once-daily amlodipine was markedly superior to twice-daily nifedipine in the crossover study involving the hypertension patients. Amlodipine was also better tolerated than nifedipine. In the angina arm of the study, patient compliance was again better with amlodipine than with nifedipine, but there was no difference observed in the levels of tolerance between the two therapies.
 ...
PMID:Patient compliance and therapeutic coverage: amlodipine versus nifedipine SR in the treatment of hypertension and angina: interim results. Steering Committee and Cardiologists and General Practitioners involved in the Belgium Multicentre Study on Patient Compliance. 915 55

To date, the clinical utility of first-generation, shortacting calcium antagonists has not been optimal due to their multiple dosing requirements. This has led to poor compliance in some patients. In this study, the safety and efficacy of a new generation dihydropyridine calcium antagonist, amlodipine (5-10 mg once daily) were evaluated in patients with chronic, stable angina pectoris. Amlodipine monotherapy was given to 226 patients over an 8-week, single-blind period, and the responders (> or = 7% improvement in exercise time) then underwent a randomized, placebo-controlled, double-blind withdrawal phase, lasting for a further 4 weeks. Amlodipine was shown to be both effective and well-tolerated in patients with chronic, stable angina pectoris. There was no evidence for the development of tolerance to amlodipine over a total of 3 months and there did not appear to be any significant problems (of the type noted with abrupt beta-blocker cessation) associated with its withdrawal.
 ...
PMID:A double-blind evaluation of amlodipine in patients with chronic, stable angina: sustained efficacy and lack of "withdrawal phenomenon" upon abrupt discontinuation. 915 56

The purpose of the study was to compare the antianginal and hypotensive efficacy and tolerability of 8 weeks of treatment with amlodipine taken once daily and nifedipine taken twice daily in patients with stable exertional angina pectoris and mild-to-moderate hypertension. Following a 2-week placebo run-in-period 13 patients were randomized to receive amlodipine (5 to 10 mg once daily) and 8 patients to receive nifedipine (20 or 40 mg twice daily) in an 8-week treatment phase. Antianginal efficacy was assessed with angina diares, investigators, and patients global evaluations and with treadmill exercise test during placebo run-in-period and after 8 weeks of the therapy. Amlodipine significantly reduced both weekly anginal attacks and consumption of glyceryl trinitrate tablets. This effect was more pronounced compared to efficacy of nifedipine. Exercise tolerance was also improved more markedly after amlodipine than after nifedipine treatment. Amlodipine treatment resulted in significant increase in total exercise time, increase the exercise time to angina onset, increase time to ST segment depression, decrease in ST segment depression, decrease in total duration of ST segment depression and decrease in duration of pain. In patients treated with nifedipine only favourable effect was significant decrease in total duration of ST segment depression, without significant changes of other examined parameters. Both drugs decreased blood pressure with no significant change in heart rate. No serious adverse events occurred in any patients during therapy with amlodipine as well as with nifedipine. The results of the study demonstrate that amlodipine has markedly better anti-anginal efficacy than nifedipine with respect to the most of the parameters examined. However both drugs showed comparable antihypertensive action and both were well tolerated by angina patients. The good anti-anginal and hypotensive efficacy and safety of amiodipine with once daily dosage regimen makes this drug an excellent choice of treatment for hypertensive patients with severe coronary artery disease.
 ...
PMID:[Comparative study to assess the efficacy and adverse effects of amlodipine and nifedipine retard in patients with stable exertional angina and hypertension]. 938 Aug 7

The purpose of the present study was to examine the effects of a long-acting calcium antagonist, amlodipine, on the development of cardiac remodeling. Dihydropyridine calcium antagonists have been used widely for many years in the treatment of hypertension and angina pectoris. It has been reported, however, that a prototype of dihydropyridines, nifedipine, does not reduce mortality of patients with ischemic heart disease, possibly because of reflex stimulation of the sympathetic nervous system. A calcium antagonist, amlodipine, has been reported to have potential benefits by virtue of a gradual onset of action and a long duration of effects. Amlodipine (8 mg/kg per day, once a day) or nifedipine (24 mg/kg per day, three times a day) was administered to spontaneously hypertensive 12-week-old rats for 12 weeks. Left ventricular wall thickness was measured by echocardiography, and relative amounts of myosin heavy chain isoforms were assessed by pyrophosphate gels. Expressions of "fetal type" genes and type 1 collagen gene were examined by Northern blot analysis. Amlodipine and nifedipine both markedly reduced systolic blood pressure. However, the decrease in systolic blood pressure caused by nifedipine continued for no more than 8 hours, whereas the blood pressure-lowering effect of amlodipine continued for more than 16 hours post dose. Amlodipine markedly reduced left ventricular wall thickness, whereas nifedipine only weakly attenuated an increase in the wall thickness. Amlodipine, but not nifedipine, prevented an increase in the relative amount of V3 myosin heavy chain isoform and suppressed an increase in mRNA levels of beta-myosin heavy chain, skeletal alpha-actin, and type 1 collagen. Unlike nifedipine, amlodipine effectively prevented cardiac remodeling secondary to high blood pressure at biochemical levels and morphological levels. These results suggest that a long-acting calcium antagonist is more effective than a short-acting one in preventing organ injury in hypertensive subjects.
 ...
PMID:Efficient inhibition of the development of cardiac remodeling by a long-acting calcium antagonist amlodipine. 944 87

Platelets are known to contribute to the initiation and progression of coronary artery narrowing by atherosclerotic plaques. Platelets also initiate periodic occlusive coronary arterial thrombosis that leads to unstable angina and myocardial infarction. Aspirin is the most widely used platelet inhibitor. However, if blood levels of epinephrine are elevated, some of the platelet inhibition produced by aspirin is diminished. Amlodipine, a second generation dihydropyridine calcium channel blocker, was studied in a widely used dog model of experimental coronary artery thrombosis. Amlodipine 1 mg/kg alone or amlodipine 0.4 mg/kg with 5 mg/kg of aspirin I.V. completely abolished the experimental coronary thrombosis and prevented the exacerbation of coronary thrombosis by epinephrine 0.2 microg/kg/min. This protective effect did not appear until 60 minutes after the amlodipine was given, suggesting a delayed onset of action. Long-acting dihydropyridine calcium channel blockers are used in patients with hypertension, angina, and coronary artery disease. They also may offer the patient some protection against fatal or nonfatal myocardial infarction via their platelet-inhibiting effects.
 ...
PMID:Inhibition of platelet activity in vivo by amlodipine alone and combined with aspirin. 948 2


<< Previous 1 2 3 4 5 6 7 Next >>