title: [Long-term effect of organic nitrates in angina pectoris: dependence on the form of administration and mode of stress].
abstract: 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.
authors.affiliation: Zentrum der Inneren Medizin, Johann Wolfgang Goethe-Universität Frankfurt a. M.
authors.forename: W
authors.initials: W
authors.lastname: Schneider
authors.forename: W D
authors.initials: WD
authors.lastname: Bussmann
authors.forename: G
authors.initials: G
authors.lastname: Kober
authors.forename: M
authors.initials: M
authors.lastname: Kaltenbach
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D000800:Angioplasty, Balloon; D003327:Coronary Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic
chemical_list: D005996:Nitroglycerin; D007548:Isosorbide Dinitrate
vernacular_title: Die Langzeitwirkung von organischen Nitraten bei Angina pectoris: Abhängigkeit von Applikationsform und Belastungsmodus.