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)

The efficacy of PY 108-068 (75 and 150 mg/day), a new dihydropyridine calcium antagonist, was compared with placebo for treatment of chronic stable angina. Twelve patients were studied in a placebo-controlled, double-blind, randomized, crossover trial of 2 weeks each. Antianginal efficacy was assessed by the number of episodes of angina and nitroglycerin tablets consumed during each 2-week period, as well as the number of episodes of ischemia during 48-hour ambulatory monitoring and the area and severity of ST-segment depression during 16-point precordial exercise mapping. Nitroglycerin consumption (mean +/- standard error of the mean) decreased from 6.1 +/- 2.9 with placebo to 1.8 +/- 1.5 with 75 mg/day of PY 108-068 (p less than or equal to 0.03) and to 3.6 +/- 2.3 with 150 mg/day of PY 108-068 (p less than or equal to 0.01 vs placebo, difference not significant vs 75 mg/day of PY 108-068), whereas episodes of angina were reduced significantly only by the high dose (p less than or equal to 0.03) (11.1 +/- 3.9 with placebo, 6.3 +/- 2.4 with 75 mg/day of PY 108-068 and 8.1 +/- 3.4 with 150 mg/day of PY 108-068). The low dose alone significantly reduced ST-segment depression during exercise testing (p less than or equal to 0.03) (29.6 +/- 3.6 with placebo, 23.1 +/- 5.6 with 75 mg/day of PY 108-068 and 24.4 +/- 5.0 with 150 mg/day of PY 108-068), whereas neither dose significantly altered the number of episodes of ischemia during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of PY 108-068, a new calcium channel blocker, for angina pectoris. 307 40

Treatment with metoprolol (100 mg twice daily), nifedipine (10 mg 3 times daily) and both drugs combined were compared for effect on clinical variables, bicycle ergometer exercise tolerance and adverse effects in a randomized double-blind, crossover study in patients with stable effort angina (n = 62). Nitroglycerin consumption and anginal attack rate as recorded in patient diaries indicated a higher antianginal efficacy (p less than or equal to 0.001) with metoprolol and combination therapy than with nifedipine monotherapy. All exercise test variables showed a significantly higher antianginal efficacy with combination therapy than with nifedipine monotherapy (15 to 26%). The combination therapy was also better than metoprolol in all exercise variables (9 to 14%), except for onset and duration of chest pain. Furthermore, metoprolol showed a higher efficacy than nifedipine in all exercise variables (7 to 23%) except total exercise time. More adverse symptoms of peripheral vasodilation were reported for nifedipine than for metoprolol (tachycardia, flushing, headache, p less than or equal to 0.05). It is concluded that combined treatment with metoprolol and nifedipine increased antianginal efficacy compared with the monotherapies, without increasing adverse effects. In effort angina, metoprolol in these doses was more effective and better tolerated than nifedipine.
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PMID:Metoprolol, nifedipine, and the combination in stable effort angina pectoris. 308 64

The purpose of this study was to evaluate intravenous nitroglycerin given during induction of anesthesia as a means for prevention of myocardial ischemia and hemodynamic changes associated with induction, laryngoscopy, and intubation, in patients with stable angina scheduled for vascular operations of moderate duration. Forty-six patients were randomly assigned to receive either fentanyl, 3 micrograms/kg (group 1, n = 6), fentanyl, 8 micrograms/kg (group 2, n = 20), or fentanyl 3 micrograms/kg plus a continuous intravenous nitroglycerin infusion, 0.9 microgram X kg-1 X min-1 (group 3, n = 20), in addition to thiopental-pancuronium anesthetic induction, prior to laryngoscopy and intubation. The criteria for recognizing myocardial ischemia were the following: horizontal or downsloping ST segment depression equal to or greater than 1 mV, and/or ventricular arrhythmia, on CM5 recording. In group 1, myocardial ischemia occurred during laryngoscopy and intubation in four patients, and mean blood pressure (MBP), heart rate, and mean pulmonary wedge pressure (PCWP) increased significantly (P less than 0.05). Despite greater stability in MBP and heart rate in group 2, myocardial ischemia still occurred in four patients (not significantly different from group 1). Nitroglycerin added to low-dose fentanyl (group 3) produced significant reduction in myocardial ischemia (1/20) when compared with group 1 (P less than 0.01), and significantly greater stability in PCWP during laryngoscopy and intubation in comparison to groups 1 and 2. In patients with stable angina undergoing operations of short duration, the use of nitroglycerin infusion and low-dose fentanyl significantly decreases the incidence of myocardial ischemia associated with induction of anesthesia and tracheal intubation.
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PMID:Roles of fentanyl and nitroglycerin in prevention of myocardial ischemia associated with laryngoscopy and tracheal intubation in patients undergoing operations of short duration. 308 52

Nitroglycerin has long been a mainstay of the treatment of ischemic cardiac pain. The introduction of transdermal formulations and in particular the development of controlled methods of delivery have been responsible for the renaissance of clinical interest in this simple and effective treatment. The pathophysiologic abnormality accompanying myocardial ischemia affords a natural theater for the exhibition of the therapeutic utility of these preparations and methods. The means whereby nitrates induce relaxation of vascular smooth muscle are not entirely clear, but their pharmacodynamic activities are perfectly plain. In the doses used in clinical practice, nitrates exert their predominant hemodynamic effects and therapeutic benefits through their peripheral vasodilator activities. This is particularly marked in veins, although in higher doses nitrates also dilate the larger systemic and coronary arteries. Criticisms of the efficacy of transdermal formulations of nitrates in the treatment of angina pectoris have arisen largely from uncritical acceptance of a small number of studies of questionable methodologic validity. Large-scale general practice studies have invariably found that transdermal nitrate delivery systems improve the quality of life in ambulant patients: anginal attacks are reduced with a minimum of side effects. The widespread acceptance of this novel form of drug delivery has stimulated its application in other therapeutic avenues. The efficacy of transdermal nitroglycerin in the suppression of silent ischemic attacks has been demonstrated. The maintenance of benefit initiated by intravenous nitroglycerin in patients with unstable angina also broadens the use of this method of nitrate delivery. In patients with acute myocardial infarction, whether complicated by left ventricular failure or not, the nitrates, and transdermal nitroglycerin in particular, appear to hold considerable promise. Improvement of hemodynamic abnormalities may cause reduction in infarct size and fewer life-threatening arrhythmias. Even survival may be extended. The utility of transdermal nitrates in the treatment of severe chronic heart failure is less certain. But the use of higher doses and an interval regimen of administration may hold promise for such patients. Naturally, more information is required before the overall therapeutic profile of this new method of controlled nitroglycerin delivery across the whole spectrum of coronary heart disease can be fully described. Fortunately, the high level of efficacy and safety of transdermal nitroglycerin demonstrated in the majority of reported studies encourages the pursuit of such an important therapeutic target.
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PMID:The role of transdermal nitroglycerin in the treatment of coronary heart disease. 308 57

Twenty patients completed a double-blind cross-over study to determine the influence of a transdermal preparation of Nitroglycerin on exercise performance in stable angina. Angiographically proven two or three vessel coronary disease was present in all. After a base-line exercise test the active device was titrated to efficacy or side effects and the number of patches thereafter remained constant (2-6 patches per day; mean 3.5). Patients were randomly allocated to active treatment or placebo, and further exercise tests were performed at 2 hours and 26 hours after application of the device. Patients were then crossed over after one days rest to the opposite treatment group, and exercise studies repeated. Two hours after application of transdermal nitroglycerin total exercise duration increased (mean 14.0 minutes) compared to placebo (12.5 minutes) and control (12.0 minutes) (p less than 0.05). This effect was maintained at 26 hours. Exercise time to anginal threshold (angina + 1.5 mm ST segment depression) was increased at 2 hours and 26 hours with active drug by 11% compared to placebo and by 22% in comparison to control. Double product of heart rate and blood pressure was not significantly different in treated and placebo groups. Oral nitroglycerin consumption assessed during the titration phase was reduced by 71%. It is concluded that transdermal nitroglycerin significantly increases exercise capacity in patients with stable angina, with an effect that is maintained over a 24-hour period using a single dose application.
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PMID:Influence of transdermal nitrates on exercise capacity in patients with stable angina. 308 73

Intravenous nitroglycerin is frequently used in the treatment of acute myocardial infarction for its vasodilating effect on lowering both preload and afterload and in the control of ischemic heart pain. The end point for doses of nitroglycerin infusion is either relief of persistent or recurrent angina or controlling congestive heart failure by lowering left ventricular end diastolic pressure and volume. Nitroglycerin accomplishes these end points primarily through its venodilating property. Intolerable headaches or symptomatic hypotension may prevent achieving the clinical end point. Nevertheless, high doses of intravenous nitroglycerin may need to be administered to achieve a desired hemodynamic and therapeutic effect. Changes in mental status, i.e., lethargy and confusion, should be a warning sign of possible ethanol intoxication. An alcohol blood level verifies the clinical impression and gradually withdrawing the intravenous nitroglycerin is all that is necessary to effect a total recovery from this reaction.
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PMID:An unusual complication of intravenous nitroglycerin. 309 6

Nitroglycerin in sublingual, buccal and transdermal administration forms were compared in 10 patients with stable exercise-induced angina pectoris with respect to onset time of action and efficacy one and three hours after administration, using bicycle exercise to provoke chest pain. Anti-anginal and anti-ischaemic effects (as judged by influence on electrocardiographic ST depression) began within 2 minutes of application of the buccal and sublingual forms, whereas the transdermal patch did not show such effects within nine minutes of application. One and three hours after application, the sublingual form had no effect whereas both the transdermal and buccal forms significantly increased exercise capacity and improved electrocardiographic ST segment changes. The 2.5 mg buccal tablet was more effective than the 10 mg transdermal patch. An additional observation was that a light snack at 2 hours significantly decreased exercise capacity at 3 hours whether or not active treatment had been instituted.
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PMID:Onset time of action and duration up to 3 hours of nitroglycerin in buccal, sublingual and transdermal form. 309 17

Nitroglycerin delivered by transdermal patch technology has been used in angina pectoris patients as well as in heart failure. In angina pectoris patients the plasma concentrations are low over the 24 hours. Effects can be found especially during the first 12 hours after application of the drug even during steady state conditions. The effect of the drug wanes after 24 hours and some studies suggest reduced effect when the patches have been applied for seven to 14 days. The attenuated effects have been claimed to be due to tolerance. Tolerance is, however, never absolute and in other studies this phenomenon is not shown. Furthermore, rebound phenomena may develop when nitroglycerin therapy is withdrawn. The optimal doses and schemes for nitroglycerin administration thus remain to be clarified.
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PMID:Tolerance development during transdermal administration of nitroglycerin in angina pectoris. 309 45

To determine both the incidence of myocardial ischaemia and haemodynamic response to carotid cross-clamping in coronary artery disease, 30 patients undergoing carotid endarterectomy were studied with a clear history of effort related disabling angina pectoris. Myocardial ischaemia was detected by a recording of lead CM5 of the electrocardiogram. A radial arterial and a thermodilution pulmonary catheter were inserted to obtain haemodynamic measurements before and after carotid cross-clamping and unclamping. Anaesthesia was induced with increments of thiopental, fentanyl 6 micrograms X kg-1 and pancuronium. Additional fentanyl (2 micrograms X kg-1) was injected before skin incision and before carotid cross-clamping. Carotid cross-clamping results in a significant increase in both mean arterial blood pressure and capillary wedge pressure. Two patients experienced myocardial ischaemia with ST segment depression during carotid cross-clamping. Nitroglycerin infusion led to the improvement of ST segment depression. When halothane was additionally administered to patients who developed hypertension in response to carotid cross-clamping, arterial blood pressure returned to normal value. These results indicate that carotid cross-clamping increases determinants of myocardial oxygen demand and may cause myocardial ischaemia in patients suffering from angina pectoris.
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PMID:[Hemodynamic effect of the clamping of the carotid in the surgically treated coronary patient]. 310 54

Glyceryl trinitrate has been used for more than a century for the treatment of angina pectoris and, more recently, for the treatment of congestive heart failure. The introduction of transdermal delivery systems has renewed the controversy regarding the efficacy of the drug, mainly in the light of the development of tolerance. With concentrations of the order of 1 microgram/L or less, the measurement of glyceryl trinitrate in plasma is not easy: gas chromatography with electron capture detection has been used widely but recently gas chromatography-mass spectrometry has provided satisfactory results. Assay problems are most likely to be responsible for some of the unexpected results reported. Further factors which may confound the results of the study of plasma concentrations are the rapid metabolism of glyceryl trinitrate in blood in vitro, adsorption to containers and infusion sets, and the uptake and/or metabolism in vessel walls. From the intravenous infusion data, the large interindividual variability in plasma concentrations of glyceryl trinitrate is apparent. The plasma half-life is about 2 to 3 minutes; plasma clearance values reported vary from 216 to 3270 L/h, indicating extensive non-hepatic metabolism. With transdermal administration, mainly with the transdermal controlled delivery systems, plasma concentrations of glyceryl trinitrate appear to be maintained for up to 24 hours, with large interindividual variations. Despite the ability to maintain, for example with the transdermal delivery systems, relatively constant concentrations of glyceryl trinitrate, it has not been possible to find a relationship between plasma concentrations and pharmacological or clinical effects. This is in part due to the attenuation of the effects with time; from the available data it is clear that this attenuation occurs at a pharmacodynamic level (reflex adaptation and tolerance) and not at the pharmacokinetic level.
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PMID:Clinical pharmacokinetics of glyceryl trinitrate following the use of systemic and topical preparations. 310 43


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