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

Fluctuating mononitrate plasma levels in the course of 24 h are a prerequisite for prevention of nitrate tolerance in patients with angina pectoris undergoing longterm treatment. In 12 patients with angiographically proven coronary artery disease (54 +/- 7 years) effects of 50 mg Isosorbide-5-mononitrate (IS-5-MN) in a slow-release (SR) formulation on hemodynamics and exercise tolerance were evaluated after a first dose and at the end of a 1-week treatment period with 50 mg given once-daily. 1 and 2 h after medication mean pulmonary artery pressure (PAP) at rest was reduced by 30% (p less than 0.001) and 25% (p less than 0.01 respectively. During submaximal bicycle exercise (50 W, 3 min) PAP was significantly reduced by IS-5-MN by 35% (1 and 2 h after medication). At the end of exercise (discontinuation), drug-induced reductions of PAP were 19% (1 h) and 21% (2 h) (p less than 0.05), respectively. IS-5-MN led to a marked increase of exercise capacity (base-line: 396 +/- 119 W x min); 1 h: 646 +/- 153 W x min (p less than 0.01). At stress testing 2, 4 and 10 h post medication improvements were 67% (p less than 0.01), 49% (p less than 0.01) and 28% (p less than 0.01), respectively. 24 h after medication baseline values were reached again. After a 1-week treatment with 50 mg IS-5-MN SR daily, beneficial effects of the drug on hemodynamics and working capacity could be demonstrated. Again, significant effects could be shown up to 10 h after drug administration. Thus, IS-5-MN SR administered once daily proved effective in intermediate-term treatment of patients with coronary artery disease with regard to hemodynamics and exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Lack of tolerance development in interval therapy with 50 mg isosorbide-5-nitrate retard (Elantan long)]. 251 97

The aim of this study was to investigate nitrate tolerance during continuous treatment with nitroglycerin patches (NTG) as monotherapy, and to assess whether tolerance might be prevented by an overnight nitrate-free interval. Ten male patients, of mean age 53.2 years (range 41-62 years), with pathological coronary angiography and stable exercise-induced angina pectoris took part in a double-blind crossover study (two 15-day periods), during which the continuous and intermittent (12-h nitrate-free interval) application of NTG 20 mg (24 h)-1 patches were compared. Single-blind placebo was given acutely before and at the end of the crossover. Exercise testing was performed on a treadmill according to the Bruce protocol 4 and 12 h after dosing, both during placebo and at the end of the two active treatment periods. In comparison with continuous treatment, the intermittent administration of 20 mg (24 h)-1 NTG patches significantly increased ischaemic threshold and total work time at the 4th and the 12th hour. Night-time withdrawal of NTG transdermal delivery systems determined during the 15-day period a total of 11 night anginal attacks in six out of 10 patients (0.07 attacks per patient per nitrate-free interval).
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PMID:Intermittent transdermal nitroglycerin monotherapy in stable exercise-induced angina: a comparison with a continuous schedule. 251 62

Nitrates are the most frequent agents used in the treatment of ischemic heart disease. In recent years nitrates have aroused a great interest; new pharmacological and clinical studies concern the mechanism by which nitroglycerin acts on the cell, forms of drugs prepared for intravenous, transdermal or oral (spray) routes of administration as well as sustained release preparations. The complexity of mechanisms of nitroglycerin action makes that nitrates are safe drugs and their action does not depend on the functional state of the myocardium. End-effects i.e. prevention of angina or relief of pain result from nitroglycerin action on the smooth muscles of the peripheral vessels and coronary arteries, on the coronary blood flow and left ventricle as well as on general hemodynamic indices. The role of specific sites of action of nitroglycerin changes depending on various factors and angina--inducing hemodynamic disorders. The phenomenon of nitrate tolerance investigated in recent years requires further studies but the results of the available trials are of considerable practical value.
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PMID:[Effect of nitroglycerin on the cardiovascular system]. 251 64

Nicorandil, a nicotinamide derivative, is a recently developed, orally active antianginal drug with a cardioprotective activity, and its pharmacologic properties differ from those of conventional antianginal drugs. Nicorandil has the capacity to increase myocardial oxygen supply without increasing oxygen demand by reduction in preload and afterload. In isolated blood-perfused canine heart preparations, when injected into the sinus node, the atrioventricular node or the anterior septal arteries, nicorandil at dose levels doubling blood flow through the respective arteries has virtually no effect on sinus rate, atrioventricular conduction time or contractile force of ventricular muscle. This may indicate that nicorandil possesses a selective effect on the coronary vasculature rather than on the myocardium. Furthermore, the vasospasmolytic activity of nicorandil has been evidenced in in vivo and in vitro experiments. The precise mechanism by which nicorandil develops coronary vasodilating and vasospasmolytic effects remains to be elucidated, but it may be partly inferred by an increase in the potassium conductance in the membrane, a relation with cyclic guanosine monophosphate formation, or inhibition of intracellular calcium ion mobilization in the cell of coronary vascular smooth muscle. Nicorandil possesses a nitrate moiety in its chemical structure. However, it is noted that nicorandil unlike nitrates does not develop tolerance or cross tolerance to other conventional nitrates in terms of blood-pressure lowering effects and coronary vasodilating effects. Thus, nicorandil is likely to have highly beneficial properties in the treatment of angina pectoris.
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PMID:Nicorandil: animal pharmacology. 252 21

ISDN (standard release formulation) 40 mg administered 6 times daily (= 240 mg) remained effective during a 4-week treatment of patients with stable angina in terms of decreasing anginal attacks and reducing ischemic ST segment depression at stress testing in the upright position (step climbing test). The sustained antianginal activity is explained by fluctuating plasma levels, provided by rapid drug release from the standard formulation, short administration intervals and an 7-hour-night pause. When comparing acute and chronic antianginal activity of ISDN (40 mg) administered 4 times daily with regard to the type of stress testing it became evident that a marked attenuation of antiischemic activity (-35%; p less than 0.01) occurred in the supine (bicycle ergometry) but not in the upright (step climbing test) position. The most probable explanation for the significant attenuation of efficacy in the supine position is marked blood redistribution into central compartments with increase of cardiac filling pressures during chronic therapy. Rapid development of tolerance both to the hemodynamic and antiischemic effects of glycerol trinitrate within 24 hours could be shown during intravenous administration (3 mg/h) in patients with stable angina. It is concluded that the antiischemic effects of oral ISDN (standard release formulation) administered 4-6 times daily is preserved during long-term therapy due to fluctuating plasma levels. Nitrate therapy providing constant doses over time (e.g. I.V. nitroglycerin) leads to a rapid attenuation of efficacy most probably due to counter regulatory mechanisms.
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PMID:[Long-term effect of organic nitrates in angina pectoris: dependence on the form of administration and mode of stress]. 253 10

N-acetylcysteine is assumed to reverse nitrate tolerance by replenishing depleted intracellular sulfhydryl groups, but data on interactions of N-acetylcysteine and nitrates in patients with stable angina are controversial and disappointing. Therefore, we studied the effect of N-acetylcysteine on nitrate responsiveness of epicardial arteries and of the venous system (assessed as changes in effective vascular compliance) in dogs (n = 12) during long-term nitroglycerin treatment (1.5 micrograms/kg/min i.v. for 5-6 days). In dogs with nitroglycerin-specific tolerance (shift of venous or epicardial artery dilation to 15-17-fold higher dosages), N-acetylcysteine (100 mg/kg i.v.) had no dilator effect and did not alter the dose-response relations of nitroglycerin. Yet, in nontolerant dogs (n = 17), N-acetylcysteine augmented (1.5-2.0-fold) the dilation of epicardial arteries and the reduction of peripheral vascular resistance induced by 0.5-1.5 micrograms/kg/min nitroglycerin. In vitro, the augmentation of purified guanylate cyclase activity by nitroglycerin (10-100 microM) was potentiated by N-acetylcysteine (0.01-1.0 mM) in saline or in canine plasma, but N-acetylcysteine alone was ineffective. We conclude that 1) N-acetylcysteine does not restore nitroglycerin responsiveness in tolerant epicardial arteries or veins in vivo, 2) a small, tolerance-independent augmentation of nitroglycerin-induced dilation may result from N-acetylcysteine-induced extracellular formation of a stimulant of guanylate cyclase from nitroglycerin.
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PMID:Nitrate tolerance in epicardial arteries or in the venous system is not reversed by N-acetylcysteine in vivo, but tolerance-independent interactions exist. 256 37

We have presented a case in which nifedipine-induced hypotension in a patient receiving beta blocker and nitrate therapy precipitated mesenteric angina, leading to emergency exploratory celiotomy. Although paradoxic angina is an unusual complication of this antianginal therapy, it should be considered in any patient who has acute abdominal pain and hypotension while receiving this therapeutic regimen.
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PMID:Nifedipine-induced hypotension and mesenteric ischemia. 256 97

Within the last decade it became obvious that the treatment of angina pectoris alone is not sufficient. Modern goals include the optimization of anti-ischemic treatment ("silent myocardial ischemia") without compromising quality of life, as well as the reduction of fatal and non-fatal cardiac events. The failure of nitrates to continuously protect from myocardial ischemia ("nitrate tolerance") requires a modification of the current step-care recommendations for medical treatment. Numerous combinations of nitrates, betablockers and calcium channel blockers compensate for each other regarding their effects on heart rate, contractility, peripheral resistance and coronary blood flow. Recommendations for combination therapy decisively depend on the choice of the first-line drug. Only nitrates reduce myocardial preload by venodilation and substitute for EDRF-deficiency. After headaches disappear, nitrates do not affect quality of life and they are cheap. The nitrate-induced acceleration of heart rate should be compensated by the addition of beta-blockers or heart rate-decreasing calcium channel blockers. Therefore, the combination of nitrates with heart-rate-increasing calcium channel blockers, such as nifedipine, should be avoided. Many studies have proven the superiority of different double and triple therapies, as compared to their single components. A few reports, however, did not confirm this increase of anti-ischemic efficacy with combination therapy. The improvement of prognosis is proven for beta blockers without ISA in subgroups of patients with acute or post myocardial infarction and can be assumed for nitrates as well. With regard to prognosis, calcium channel blockers were inferior to nitrates and beta blockers. The combination of nitrates with a non-ISA betablocker should be preferred in post myocardial infarction patients with ventricular arrhythmias, whereas the combination of nitrates with a heart rate decreasing calcium channel blocker should be preferred in patients with COPD, severe peripheral arterial disease or severe diabetes. The combination of nitrates with a heart-rate-increasing calcium channel blocker should be considered in patients with sinus bradycardia, first degree AV-block, or proven coronary spasm. In patients with congestive heart failure, betablockers and calcium channel blockers should be avoided. To optimize medical treatment of ischemic heart disease, intermittent high dosage ISDN plus a beta blocker without ISA or ISDN plus a calcium channel blocker like verapamil are recommended. Frequently, however, the patient decides by himself, based on unacceptable side effects.
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PMID:[Combination of anti-angina drugs]. 257 81

The authors describe the development of nitrates from substances of the first generation (nitroglycerin and isosorbide dinitrate) to the use of mononitrates. They explain the mechanism of their action, the haemodynamic effects and the phenomenon of nitrate tolerance. The authors present also their own experience with nitrate therapy in angina pectoris and heart failure based on haemodynamic monitoring and recommend its rational use.
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PMID:[The development and use of nitrate therapy]. 262 Mar 35

Calcium antagonists and beta-blockers may retard or inhibit atherogenesis. We tested whether nifedipine or propranolol may retard or induce regression of coronary atherosclerosis in man. In selected population of 113 patients with effort angina and proven coronary artery disease, the coronary cineangiographic pattern after 2 year therapy with nifedipine (Group 1, 39 patients), propranolol (Group 2, 36 patients), or isosorbide dinitrate (control group, 38 patients) was compared to the pre-treatment pattern. After 2 years the disease evolved to a different extent in the 3 groups. The number of lesions with evidence of progression was significantly smaller after nifedipine (14), and larger after propranolol (39) as compared with controls (24). Patients with evidence of progression of old lesions, and appearance of new lesions were significantly fewer in Group 1 than in Group 2 and in control patients. Thus, nifedipine seemed more protective than either of the other drugs against coronary atherosclerosis. The coronary risk factors were within normal limits in the nifedipine treated group and remained so with treatment supporting that they were likely dissociated from influences on atherosclerosis. The evolution, at least as judged by the number of lesions with progression, appeared significantly (p less than 0.01) worse with propranolol than with isosorbide dinitrate. This may prospect that nitrate contrasted the evolution of the disease, or that propranolol made it worse, possibly through unfavourable modifications of serum lipids (28% rise of total triglyceride and 25% decrease of HDL cholesterol were already detectable at 12 months in Group 2).
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PMID:[Angiographic course of coronary atherosclerosis in angina pectoris. Its relation to 2 years' treatment with propranolol, nifedipine and nitrates]. 263 89


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