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)

Eight men with stable angina, a positive treadmill test, and demonstrated responsiveness to chronic oral isosorbide dinitrate (ISDN) were studied after they had been taking effective doses of ISDN t.i.d. for at least 2 weeks. Exercise tests were performed every 1-2 h until 19.00 hours over one day after the 08.00 hours application of nitroglycerin patches in a previously titrated dose; on another day after the administration of ISDN capsules q5h; and on a third day after placebo patches and capsules. The mean necessary effective patch dose was 125 cm2 (60-220 cm2). The mean exercise duration to angina rose from 271 to 480 s 1 h after nitroglycerin patches (P less than 0.001). Nitroglycerin patches were superior to the placebo throughout the day, but in a declining degree--by 94 s at 19.00 hours (P less than 0.05). ISDN q5h provided peaks of increased walking time to angina 1 h after each dose, but after 3 h exercise time was down to placebo levels. Furthermore, the peaks were of diminishing amplitude: 200 s at 09.00 hours, 150 s at 14.00 hours, but only 70 s at 19.00 hours. Thus, neither nitrate regimen provided continuous near-peak benefit throughout the 11 h period, although nitroglycerin patches had a significantly greater (P less than 0.05) overall effect during the day.
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PMID:A comparison of the day-long antianginal effectiveness of nitroglycerin patches with that of three-times-daily isosorbide dinitrate: a double-blind study using dose titration. 139 39

The beneficial effects of nitrates in patients with angina pectoris and acute myocardial infarction have positively influenced the prognosis of the treated patients. Studies of Jugdutt pointed out that there is a better prognosis also in the postinfarction period. Especially left ventricular over dilatation, which follows larger infarct, can be prevented by a consistent nitrate therapy.
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PMID:[Therapy with nitrates in the post-infarct phase]. 144 Oct 71

The rapid development of tolerance has limited the applicability of oral and transdermal nitrates in the long-term management of patients with chronic stable angina pectoris. Recent well-controlled trials have demonstrated that asymmetrical, or eccentric, dosing of oral isosorbide mononitrate, in which 20-mg doses are taken at 8 A.M. and 3 P.M., provides at least 12 hours of antianginal coverage. There is no evidence for the development of tolerance with this schedule, which allows for a 17-hour nitrate withdrawal period. Likewise, the asymmetrical 20-mg twice daily regimen has not been associated with the zero-hour effect that has been reported with higher oral doses of isosorbide mononitrate and with intermittent nitroglycerin patch therapy. This approach also avoids the development of a clinical rebound phenomenon, as measured by increased episodes of angina and nitroglycerin consumption, compared with the pretreatment period, during the nitrate-free interval at night and the early hours of the morning.
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PMID:Efficacy of isosorbide mononitrate in angina pectoris. 144 3

The organic nitrates have remarkably diverse actions that are or should be beneficial in patients with ischemic heart disease. These drugs are effective in all the important ischemic syndromes. Preliminary data in patients with acute infarction suggest that the drugs may be truly cardioprotective, resulting in improved mortality. This review has not discussed the role of nitrates in congestive heart failure or LV dysfunction, a subject of great importance. The nitrates are useful adjunctive agents in these syndromes, and the two VeHfT trials support the concept that long-term nitrate administration, in conjunction with hydralazine, may favorably alter the natural history of heart failure. This cardioprotective effect is similar to that suggested for the post-MI patient. The data are not strong enough for definitive conclusions at this time. The clinical benefits of nitrates in decreasing subjective (angina) and objective indices of ischemia in stable and unstable angina, as well as limited data in asymptomatic myocardial ischemia, are unequivocal and are as favorable as those for beta blockers or calcium antagonists. Tolerance is an important problem that unfavorably influences the potential benefits of nitrate therapy. I believe that this problem can be avoided with well-designed dosing regimens. Current research into endothelial biology in health and disease has further supported a physiologic role for the organic nitrates in patients with ischemic heart disease. The nitrate-platelet story, while controversial, is promising and offers another positive rationale for nitrate administration. The concept of nitrates replenishing disordered EDRF release or action is an exciting one. Physicians should feel fortunate to have such a remarkable group of drugs available for their patients.
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PMID:Use of nitrates in ischemic heart disease. 151 14

Nitrates are used extensively for the treatment of angina pectoris. However, continuous therapy with either oral nitrates or nitroglycerin patches leads to rapid development of tolerance, with loss or diminution of antianginal and anti-ischemic effects. The only practical way to avoid the development of tolerance is to use intermittent daily therapy with nitrates. Nitroglycerin patches applied for 10-12 hours during the day increase exercise duration for 8-12 hours, but a rebound increase in anginal attacks during the nitrate-free interval may occur. Oral isosorbide-5-mononitrate, 20 mg twice a day, with the first dose administered in the morning and the second dose 7 hours later, increases exercise duration for at least 12 hours without the development of tolerance to either the morning or afternoon dose. This dosing regimen has been shown not to produce a rebound phenomenon during the periods of low nitrate levels at night and early hours of the morning. Isosorbide dinitrate (30 mg) prescribed at 7 AM and 1 PM does not produce tolerance to the 7 AM dose, but effects of the afternoon dose have not been evaluated. Recent data suggest that isosorbide dinitrate given 3 or 4 times daily produces tolerance and this dosing schedule is inadequate for antianginal prophylaxis. It should be recognized that intermittent oral or patch therapy with nitrates during the day leaves the patient unprotected at night and early hours of the morning. If this is of concern, additional therapy with another class of antianginal agent, preferably a long-acting beta blocker or a long-acting calcium antagonist should be instituted.
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PMID:Role of nitrates in angina pectoris. 152 26

Daily life ischemia has generated considerable interest because most of it is silent and associated with increased risk of adverse outcome. Coronary vasomotion, as well as increases in myocardial oxygen demand, seem important in the pathogenesis of this form of ischemia, so treatment with nitrates seems rational. Administration of sublingual nitroglycerin hourly, over 12 hours, was shown to decrease both silent and painful ischemic episodes in patients with effort angina. Subsequently, isosorbide dinitrate or mononitrate, given either as an intravenous infusion or orally, was shown to decrease both silent and painful ischemic episodes in patients with unstable rest angina and in those with severe angina. More recently, 6 studies have reported using transdermal nitroglycerin for daily life ischemia. Three of these reported open-label uncontrolled observations and suggested that ischemia frequency may be reduced approximately 60-80% during treatment with doses of 10-30 mg/day, with a duration of treatment ranging from 1 hour to 14 days. In 2 of these reports the duration of ischemia also decreased. The other 3 studies were randomized, double-blind, placebo-controlled studies with a total enrollment of 86 patients. These studies provided mixed results. One suggested that evidence for partial tolerance develops within 1 day of treatment, using large continuous or intermittent doses (mean, 52 mg/day). Another suggested that no tolerance develops to intermittent dosing (18 mg/16 hr out of 24 hr) during exercise testing but no effect is seen on daily life ischemia. The remaining study suggested that tolerance does not develop using small doses (15 mg/day) continuously over 14 days for ischemia during daily life, and that this response is different from that observed using the calcium antagonist nifedipine. These limited observations and conflicting results underscore a need for additional larger controlled trials, employing topical nitrate therapy in low intermittent doses for daily life ischemia.
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PMID:Daily life ischemia and nitrate therapy. 152 27

A new galenic form of isosorbide dinitrate (consisting of a hydrophilic matrix which allows very slow release of the active drug) was studied from the pharmacokinetic and pharmacodynamic view points in 11 patients with stable angina pectoris under betablocker therapy. After testing their sensitivity to nitrates with a sublingual trinitrin test causing a fall greater than or equal to 20 mmHg in systolic and greater than or equal to 10 mmHg in diastolic blood pressure, the patients were given a single tablet of Risordan LP 80 daily for 7 days. The equilibrium plasma concentrations of isosorbide dinitrate and its mononitrate metabolites (2-isosorbide mononitrate and 5-isosorbide mononitrate) over 24 hours were measured on the 6th treatment day. A method of measuring these nitrate derivatives has been developed and validated. The concentrations measured enabled the study of the pharmacokinetics of this new form, showing an average minimal concentration of 5-isosorbide mononitrate (principal metabolite) of 85 +/- 41 micrograms/l and an amplitude of fluctuation over the 24 hours period of 296 +/- 102 micrograms/l. From the pharmacodynamic point of view, the evaluation of the sensitivity to a single dose of 0.75 mg of trinitrin 24 hours after the first dose of Risordan LP 80, just before the second dose and 24 hours after the seventh dose, showed a significant difference (average decrease of 40 +/- 19 mmHg in systolic blood pressure) with respect to the values observed during the selection phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pharmacokinetics and pharmacodynamics of a new 80 mg oral delayed-action isosorbide dinitrate preparation]. 153 Apr 22

The daily plasma level fluctuation is critical in the prevention of tolerance during long-term nitrate therapy. Two dosage regimens of sustained-release isosorbide dinitrate (ISDN) (60 mg tablet once daily vs 20 mg three times daily) were compared at steady state. Comparative bioavailability data of the two forms after single administration in 12 healthy subjects enabled calculation of the steady state blood levels of ISDN, IS-2MN and IS-5MN by simultation of the two regimens. Both achieved the required trough concentration to restore sensitivity to nitrates (100 micrograms/l for IS-5MN), but greater plasma level increases were observed (greater than 200 micrograms/l for IS-5MN), with 60 mg once daily. A parallel, randomised, double-blind, double placebo study involved 126 patients with stable angina, concomitantly receiving beta-blockers and/or calcium inhibitors. Ergometric parameters 4 hours after drug administration and clinical symptoms were compared at inclusion under 20 mg three times daily, and after a 4 week treatment with either dosage. Compared with 20 mg three times daily, the once daily regimen: improved equally the symptoms and ergometric parameters of stable angina in combination therapy; had a similar side-effect profile; enhanced the sensitivity to nitrate 4 hours after administration with regard to the hypotensive effect; the latter may clinically reflect the pharmacokinetic differences between the two regimens. Sixty milligrammes sustained release ISDN once daily may thus avoid nitrate tolerance and improve patient compliance.
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PMID:[Nycthemeral changes in plasma concentrations of active nitrate derivatives. Comparison of a single dose of LP 60mg isosobide dinitrate and LP 20mg isosobide dinitrate administered 3 times daily]. 153 Apr 23

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.
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PMID:[Differential action of nitrate derivatives and arterial vasodilators on coronary circulation. An experimental approach and therapeutic consequences]. 153 Apr 32

The action of nitrate derivatives on the coronary arterioles is weak and very short lasting which avoids the phenomenon of a coronary steal syndrome. Investigations of the epicardial coronary vessels require vasoconstriction stress tests, usually using ergometrine, and vasodilatation tests, mainly using isosorbide dinitrate (ISDN). The combination of the two tests allows evaluation of global coronary vasomotricity which is less than 100% variation of diameter. In coronary spasm, ISDN relieves the stenosis in less than 2 minutes in nearly all cases. An infusion of ISDN also prevents most cases of arterial spasm. In effort angina, it has been possible to demonstrate paradoxal vasoconstriction during exercise due to endothelial dysfunction. The direct action of nitrate derivatives on smooth muscle which is not endothelium dependent, prevents the vasoconstriction and increases oxygen supply during exercise.
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PMID:[Nitrate derivatives and coronary vasomotricity]. 153 Apr 33


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