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)

The discovery of endothelial regulatory properties in the modulation of the vascular response to pharmacological agents and its fundamental role in the phenomenon of flow-dependence has enabled the demonstration of the mode of action of coronary vasodilators on the large epicardial vessels where most coronary spasm occurs. Nitrate derivatives are remarkably selective in their effects on the large vessels which dilate in an endothelial-independent manner, which makes them very effective in the prevention and treatment of coronary spasm occurring, for example, during angioplasty. On the other hand, arterial vasodilators, like calcium antagonists or potassium agonists have decreased vasodilatory effects on these conductance vessels in the presence of endothelial lesions as their action is partially or entirely endothelium-dependent. By their additive coronary vasodilator effects, the association of these two groups of vasodilators provides greater therapeutic efficacy in the prevention of angina whatever its cause.
 ...
PMID:[Differential action of nitrate derivatives and arterial vasodilators on coronary circulation. An experimental approach and therapeutic consequences]. 153 Apr 32

Nitrate therapy has been shown to be beneficial for the treatment of coronary artery diseases and a number of chemical entities and their respective pharmaceutical formulations are available for clinical use. In this report, the performance of these nitrate drug/formulation combinations is discussed in terms of the relative onset of action, duration of action, tolerance properties/regeneration of reactivity and patient acceptance. A pharmacodynamic action scheme is presented and this allows a systematic assessment of how changes in the nitrate and/or formulation may impact on therapeutic activity. Data suggest that several sustained-release preparations of various nitrates can provide protection against exercise-induced angina for about 12 h on repeated dosing, provided a 'nitrate-free' or 'nitrate-poor' interval is also instituted. The 'ideal' nitrate substance and formulation, which theoretically can provide around-the-clock protection, is not yet available.
 ...
PMID:Nitrate therapy: is there an optimal substance and formulation? 187 73

Nitrate preparations are useful in the treatment of acute and chronic angina, acute and chronic congestive heart failure, and acute myocardial infarction. Development of tolerance is best managed by providing a nitrate-free interval, thus avoiding continuous drug levels. This interval probably should be 10 to 12 hours with use of a transdermal patch. Nitrate treatment of the elderly may require lower doses to avoid hypotension.
 ...
PMID:A practical guide to nitrate use. 189 77

25 patients with stable angina pectoris after acute myocardial infarction were given single and maintenance doses of isosorbide-5-mononitrate (IS-5-MN) in a controlled-release formulation. For evaluation of the efficacy of this treatment, a score based on exercise tests and patient's complaints including additional antianginal medication were used 4 weeks after the acute event. For assessment of anti-ischemic effect non-invasive parameters including heart rate, arterial blood pressure, changes in ST segments, frequency of premature ventricular beats and systolic time intervals were used before medication, 5 h after the initial dose and 7 days after maintenance therapy. The therapeutic concept of interval treatment was found to be effective. Nitrate tolerance did not develop. Measurements of plasma levels under steady-state conditions revealed minimum values of 100 ng/ml and maximum levels of 460 ng/ml which is in between the threshold for anti-ischemic effect and development of nitrate tolerance, respectively.
 ...
PMID:Anti-ischemic and antianginal effects of 60 mg isosorbide-5-mononitrate in patients treated chronically after myocardial infarction. 235 14

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.
 ...
PMID:[Long-term effect of organic nitrates in angina pectoris: dependence on the form of administration and mode of stress]. 253 10

The symptomatic benefits of combining beta-adrenoceptor blockers and nitrates in angina pectoris are well recognised. Their actions on cardiac haemodynamics and volumes when combined have been poorly characterized. Accordingly this study investigated a new cardioselective beta-adrenoceptor blocking agent celiprolol and buccal nitroglycerine in 24 patients with angiographically documented coronary artery disease. Following a control period, with confirmed stable haemodynamics, three groups (n = 8/group) of prospectively matched patients, were studied following intravenous celiprolol (8 mg), buccal nitrate (10 mg) or their combination. Haemodynamics and left ventricular ejection fraction (nuclear probe) were determined following each intervention. The actions of each regimen on the haemodynamics of exercise-induced angina were compared by exercise testing in the control state and following each regimen. At rest, celiprolol did not alter haemodynamic parameters. Nitrate therapy reduced left ventricular filling pressure (pulmonary artery occluded pressure--PAOP) and volumes; the ejection fraction and heart rate increased. Combination therapy resulted in a highly significant reduction in left ventricular preload and afterload (PAOP and mean arterial blood pressure) at an increased left ventricular ejection fraction and reduced cardiac volumes; there was a trend to reduce cardiac double product (HR X SBP). During exercise celiprolol reduced systolic blood pressure, heart rate and cardiac index; systemic vascular resistance index increased. Nitrate therapy reduced blood pressure and PAOP, and increased ejection fraction. Combination therapy reduced all components of the triple product (heart rate, systolic blood pressure and PAOP) without affecting the other haemodynamic or radionuclide parameters. These data suggest improvements in cardiac function from the combination of celiprolol and nitrate therapy which were not achieved by either agent when used as monotherapy; they afford an interesting insight into the manner in which such widely utilised therapeutic modalities interact in coronary artery disease.
 ...
PMID:A rest and exercise haemodynamic evaluation of a new cardio-selective beta-adrenoceptor blocker celiprolol alone and in combination with nitroglycerine in ischaemic heart disease. 288 72

Nitroglycerin and the long-acting nitrates are beneficial in stable and unstable angina pectoris and acute myocardial infarction and as adjunctive therapy in congestive heart failure. Nitroglycerin compounds relax vascular smooth muscle, producing venous, arterial, and arteriolar dilatation. These actions are modulated by stimulation of intracellular cyclic guanosine monophosphate. Nitrate efficacy in ischemic heart disease is due to peripheral venous and arterial vasodilatation that results in decreased myocardial oxygen consumption. Nitrates also dilate coronary arteries and collaterals, reverse coronary vasoconstriction, and enlarge some coronary atherosclerotic lesions. Nitrates improve exercise performance in stable angina pectoris. Intravenous nitroglycerin should be used in the initial treatment of unstable angina. Nitrates may be beneficial in myocardial infarction for control of ischemic pain, acute hypertension, and left ventricular failure. In subjects with congestive heart failure, nitrates reduce symptoms and improve exercise tolerance. Nitrate tolerance is a problem with continuous nitrate therapy. Tolerance is most likely to occur with frequent dosing or the use of long-acting nitrates, particularly transdermal nitroglycerin disks, and can be prevented or reversed with intermittent-dosing regimens.
 ...
PMID:A reappraisal of nitrate therapy. 327 14

Calcium channel blockers, nitrates, and beta blockers are the primary agents used for the treatment of angina. Calcium has a central role in excitation-contraction, action potential generation, and ischemic cell death. The three currently available calcium antagonists are nifedipine, verapamil, and diltiazem. Second-generation agents are in development, and a classification system of calcium channel blockers is used to place the currently available agents and those on the horizon in perspective. Nitrate pharmacology and pharmacodynamics are possibly related to nitrate tolerance; however, this is a matter of some controversy. The beta blockers are all equally effective in the treatment of angina; therefore, drug selection is based on ancillary properties.
 ...
PMID:Pharmacologic and pharmacokinetic comparison of antianginal agents. 332 60

Nitrates are presently used in the therapy for angina pectoris. They have both direct coronary vascular and indirect systemic effects; each appears to contribute to their anti-anginal efficacy. The various nitrate preparations, including the newer preparations recently made clinically available, have varying utilities in the relief of acute ischemic pain or for anginal prophylaxis. Nitrate tolerance and dependence are proved phenomena, yet their impact on the clinical usage of nitrates is not clearly defined. The utility of nitrates, including intravenous nitroglycerin, in the treatment of unstable angina and vasospastic angina is well documented. Their efficacy compared with that of calcium channel blockers is still being investigated. The reported adverse effects of nitrates are few, despite their many years of usage in clinical medicine.
 ...
PMID:Nitrate therapy for angina pectoris. Current concepts about mechanism of action and evaluation of currently available preparations. 391 68

Ten patients with angiographically proven coronary heart disease, stable exercise-induced angina pectoris, and reproducible ST-segment depression were treated with isosorbide dinitrate (ISDN) tablets in daily doses of 240 mg (6 X 40 mg) and placebo (PL) for 28 days each on the basis of a randomized double-blind protocol with intraindividual cross-over. ISDN treatment resulted in a sustained reduction of anginal attacks with a weekly mean rate ranging from 1.4 (3rd week) to 3.9 (4th week) as compared to 10.2 (2nd week) to 11.7 (4th week) during placebo treatment (P less than 0.001). Ischemic response during stress testing (sum of ST-segment depressions) was significantly improved during ISDN treatment as compared to placebo. Day 1: 56% (P less than 0.01); day 7: 30% (P less than 0.01); day 28: 49% (P less than 0.001). Heart rate and arterial blood pressure in the upright position were different between ISDN and placebo on day 1 and day 7 of the treatment phases (P less than 0.02), but not on day 28. Nitrate responsiveness with regard to blood pressure and heart rate was restored after a drug-free interval of 2 days. The plasma concentrations for ISDN and the mononitrate metabolites exhibited a constant ratio during the treatment period. Thus, therapy with 6 X 40 mg ISDN per day resulted in a sustained reduction of anginal attacks and preserved improvement of ischemic ST-segment depression during exercise in upright position.
 ...
PMID:[Anti-angina effectiveness of isosorbide dinitrate in an acute trial and following continuous 4-week therapy with 40 mg 6 times a day]. 392 17


1 2 3 4 Next >>