Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amlodipine is a dihydropyridine calcium antagonist that has unique pharmacokinetic properties. The drug is absorbed gradually after oral administration and so produces a gradual vasodilatation, reducing the incidence of side effects such as reflex tachycardia and headache, which can be troublesome with other calcium antagonists. Amlodipine also has a long elimination half-life, which makes it suitable for use on a once-daily basis. Controlled clinical studies have confirmed that a suitable dose regimen of amlodipine for use in angina is to start with 5 mg daily and increase this to 10 mg daily if required to control symptoms. Exercise testing carried out 24 hours post dose has confirmed that once-daily doses of amlodipine provide good anti-anginal and anti-ischaemic efficacy for a full 24 hours, a vital aspect of any therapy for ischaemic heart disease. Amlodipine has been shown to have comparable anti-anginal efficacy to the beta-blocker nadolol taken once daily and the calcium antagonist diltiazem taken 3 times daily. When added to the treatment regimen of patients with uncontrolled chronic stable angina despite treatment with nitrates, beta-blockers or both, amlodipine produces improved anti-anginal efficacy. Amlodipine has also been shown to be consistently effective in patients with vasospastic angina. There has been no evidence of tolerance to the anti-anginal effects of amlodipine in formal clinical trials involving treatment for up to 26 weeks.
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PMID:The efficacy of amlodipine in the management of ischaemic heart disease. 183 71

Amlodipine is a novel dihydropyridine calcium antagonist with distinctive pharmacokinetic and pharmacodynamic properties, including slow onset and long duration of action, with minimal effects on cardiac electrophysiology and myocardial contractility. These unique pharmacokinetic and pharmacodynamic properties are believed to be related to the unusual physiochemical profile of amlodipine. Thus, despite being more polar than other dihydropyridines, due to the presence of a charged amino function, amlodipine shows exceptionally high affinity for biological membranes, possibly due to an electrostatic interaction with membrane phospholipid. This results in a large volume of distribution and hence a long elimination half-life. Results obtained from studies involving ischaemic/reperfused rat, cat and dog hearts showed that amlodipine had a protective effect on the ischaemic myocardium. Treatment with amlodipine was found to reduce myocardial oxygen demand, improve recovery of peak developed tension, have a favourable effect on Ca2+ fluxes, improve retention of tissue adenosine triphosphate and creatine phosphate, and reduce acidosis in the ischaemic/reperfused myocardium. Amlodipine therefore accelerated the recovery of both mechanical myocardial function and blood flow, producing a favourable effect on contractile and metabolic recovery, suggesting that amlodipine may have potential as a therapeutic agent in the treatment of ischaemic heart disease. The long duration of action associated with amlodipine may be of benefit in ischaemic heart disease, as an increase in myocardial ischaemia has been observed in the early hours when plasma levels are normally at their lowest.
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PMID:The pharmacological profile of amlodipine in relation to ischaemic heart disease. 183 72

Amlodipine is a dihydropyridine derivative belonging to the group of pharmacologic calcium entry blocking agents and is characterized as having a slow onset and relatively long duration of action with minimal effects on cardiac electrophysiology and myocardial contractility. The protective effect of amlodipine was studied in isolated blood-perfused feline hearts made globally ischemic for 60 minutes followed by reperfusion for 60 minutes. Ischemic-induced alterations of left ventricular developed pressure and complicance were monitored. In 11 control and 7 drug-treated hearts, amlodipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). Amlodipine administered before the onset of global ischemia decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 minutes afer reperfusion, improved significantly in the amlodipine-treated group compared with controls, and there was better maintenance of the tissue concentration of Na+, Ca2+ and K+. A canine model of regional myocardial ischemia (90 minutes) followed by 6 hours of reperfusion was used to assess the cardioprotective effects of amlodipine, 150 micrograms/kg, administered 15 minutes before reperfusion. Infarct size, expressed as a percentage of the area at risk, was smaller in the amlodipine-treated group (n = 10) than in the control group (n = 10) (34.5 +/- 3.8% vs 45.9 +/- 2.8%, p = 0.027). Risk region size did not differ between groups and both groups were comparable with respect to the hemodynamic parameters of heart rate, blood pressure and rate-pressure product. Amlodipine prevented the gradual reduction in coronary blood flow observed in the control group. It is concluded that amlodipine reduces myocardial ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen demand as well as by positively influencing transmembrane Ca2+ fluxes during ischemia and reperfusion.
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PMID:Cardioprotective effects of amlodipine in the ischemic-reperfused heart. 253 Aug 82

The effects of amlodipine, a novel, long-lasting calcium channel blocking agent, on ischemia-induced myocardial conduction delay was studied in anesthetized pigs paced at a constant heart rate. Acute coronary occlusion (3 minutes) significantly lengthened time to onset, time to peak and duration of bipolar electrograms recorded from both subendocardial and subepicardial left ventricular sites. After intravenous injection of amlodipine (0.3 mg/kg, n = 6), subsequent periods of ischemia greatly reduced (p less than 0.01) all indexes of subepicardial conduction delay. In the subendocardium, amlodipine decreased only time to onset (-25 +/- 4%, p less than 0.01) within the ischemic zone. Significant delays in all indexes were present during repeated ischemic periods in the placebo-treated control group (n = 5). Amlodipine also increased regional myocardial blood flow within the nonischemic myocardium by 25 +/- 10% and decreased mean aortic pressure by 7 +/- 2% without altering flow in the ischemic region. Left atrial pressure remained unchanged. Indexes of ischemia-induced conduction delay were more rapidly restored after reperfusion in amlodipine-pretreated than in control animals. In conclusion, amlodipine produced a beneficial blood flow-independent effect on ischemia-induced injury potentials. The effect may help to reduce the likelihood of development of lethal ventricular arrhythmias in the early stage of myocardial ischemia in the clinical setting.
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PMID:Amlodipine, a long-acting calcium antagonist drug reduces ischemia-induced ventricular conduction delay in pig hearts. 253 Aug 89

Calcium antagonists are among the most potent and efficacious drugs used in the treatment of angina pectoris. Amlodipine, a new member of this family of dihydropyridines, has a unique pharmacokinetic profile with high bioavailability and an extended period of pharmacodynamic activity. In formal randomized, double-blind, placebo-controlled trials with exercise tests carried out 24 hours after administration, amlodipine was significantly more effective than the placebo and comparable in efficacy with the calcium antagonist diltiazem and the beta-blocking drug nadolol. In addition to extending exercise capacity in patients with angina pectoris, amlodipine significantly reduces ECG evidence of myocardial ischemia. Amlodipine has also been found to be effective in reducing the anginal attack rate in patients with vasospastic angina. From the evidence available, it is concluded that once-daily treatment with amlodipine in the dose range of 5 to 10 mg is effective in improving exercise capacity and reducing anginal attack rate in patients with chronic stable angina pectoris and also those with vasospastic angina.
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PMID:The efficacy of amlodipine in myocardial ischemia. 257 66

The haemodynamic dose-response effects of a new long-acting slow-calcium channel blocking agent, amlodipine were evaluated in 20 patients with angiographically confirmed coronary heart disease. At rest, following a control saline period, four i.v. doses of the drug (cumulative dosage 1.25, 2.5, 5 and 10 mg) were administered to ten patients and haemodynamics determined in the ten to 15 minutes following injection. Effects on circulatory parameters were only evident following the maximum cumulative dosage. Accordingly in a further ten patients, the regimen was doubled (cumulative i.v. dosage 2.5, 5, 10 and 20 mg). In each study the haemodynamic effects during constant load supine bicycle exercise were evaluated by comparison of values during the control exercise period and following the final cumulative dosage. On the higher regimen, amlodipine significantly reduced resting systolic, diastolic and mean (p less than 0.01) systemic arterial pressure and systemic vascular resistance index (p less than 0.01). Heart rate (p less than 0.01), stroke volume index (p less than 0.01) and cardiac index (p less than 0.01) increased; pulmonary artery occluded pressure was unchanged. During constant load bicycle exercise, the mean arterial pressure was significantly reduced (p less than 0.01), and the heart rate and cardiac index increased (p less than 0.01). Thus the immediate impact of amlodipine in stable coronary artery disease was to reduce left ventricular afterload and augment cardiac pumping performance. The minimum effective i.v. dosage appeared to be 10 mg. Amlodipine appears sufficiently promising to warrant longer-term studies in ischaemic heart disease.
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PMID:A haemodynamic dose finding study with a new slow-calcium channel blocker (amlodipine) in coronary artery disease. 295 40

Calcium antagonists are effective antianginal agents in the treatment of patients with stable exercise-induced angina pectoris. A series of randomized, double-blind, placebo-controlled studies with the novel, once-daily calcium antagonist amlodipine have been completed in a large number of patients with stable exercise-induced angina pectoris. Compared with placebo, once-daily amlodipine demonstrated a significant dose-related extension in exercise duration and workload accomplished, and reduction in number of anginal attacks and associated glyceryl trinitrate consumption. The clinical antianginal attributes of amlodipine were accompanied by significant reductions in electrocardiographic evidence of myocardial ischemia. In comparison with other antianginal drugs, once-daily amlodipine at a dosage range of 5-10 mg demonstrated antianginal activity comparable to thrice-daily diltiazem and once-daily nadolol. Amlodipine administered once daily achieves symptomatic and electrocardiographic amelioration of myocardial ischemic episodes induced by exercise in the majority of patients with stable angina pectoris. Amlodipine does not depress left ventricular pumping activity, and its side-effect profile does not differ substantially from that of placebo.
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PMID:Usefulness of amlodipine for angina pectoris. 831 Sep 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.
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PMID:Mechanism of the antiischemic effect of mibefradil, a selective T calcium channel blocker in dogs: comparison with amlodipine. 865 47

Anginal symptoms alone are not a reliable guide to the extent of patients' ischaemic heart disease and silent episodes of ischaemia are associated with increased morbidity and mortality. It is becoming apparent that effective treatment of ischaemia will have to target the pattern of ischaemic events seen in patients' daily lives and treatment strategies are now being developed which aim to eliminate both silent and symptomatic episodes of ischaemia over the whole 24-h period. For example, the Circadian Anti-ischaemia Program in Europe (CAPE) trial has shown that significant improvements in objective and subjective measures of ischaemia occurred over 24 h when the once-daily third-generation dihydropyridine calcium antagonist amlodipine was added to background medical therapy. In addition, the Canadian Amlodipine/Atenolol in Silent Ischaemia Study (CASIS) has clearly shown the complementary effects of combination therapy with amlodipine and the long-acting beta-blocker atenolol. Ongoing and future outcome studies will determine the impact of such approaches on the prognosis for patients with ischaemic heart disease.
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PMID:Treatment effects on the total ischaemic burden and prognostic implications. 896 Apr 59

Calcium antagonists may reduce propensity to ventricular fibrillation, by altering the balance between coronary blood flow and metabolic demand, and thus may substantially prolong time to occurrence of fibrillations. This delay in the onset of fibrillation should be sufficient to prevent sudden death in the case of transitory episodes of myocardial ischemia. Therefore, this study was based on the determination of time to onset of fibrillation in an animal model of transitory ischemia. This model was achieved by the complete, but transitory occlusion of the left anterior descending coronary artery near its origin under ventricular pacing at a constant high rate (180 beats/min), in anesthetized, open-chest pigs. Amlodipine was preferred to another calcium antagonist for this study because it is among the least negatively inotropic of these drugs. It was intravenously infused at 0.02 mg.kg-1.min-1. Time to fibrillation was prolonged from 87 +/- 10 to 146 +/- 16 s (p < 0.05) with the 0.30 mg/kg dose and to 201 +/- 22 s (p < 0.05) with the 0.60 mg/kg dose, without serious impairment of blood pressure or left ventricular dP/dtmax in the absence of ischemia. Concurrently, amlodipine significantly limited the shortening of monophasic action potential duration (200 +/- 4 vs. 172 +/- 6 ms), the lengthening of conduction time (43 +/- 2 vs. 53 +/- 2 ms), and the alterations of ST segments and T waves induced by 60 s ischemic depolarization. Consequently, amlodipine might reduce the incidence of sudden death by lengthening time to onset of fibrillation beyond the duration of the ischemia, when transitory.
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PMID:Possible prevention by amlodipine of ventricular fibrillation related to brief ischemia episodes. 904 40


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