title: Lack of tolerance after chronic administration of controlled-release isosorbide-5-mononitrate. Interaction of nitrate and gallopamil.
abstract: The effect of a controlled-release formulation of isosorbide-5-mononitrate (IS-5-MN) was studied in patients with coronary heart disease (CHD), with the aim of comparing the acute effect with that after chronic administration on parameters of ischemia. To determine whether any tolerance developed, several aspects of ischemia were observed: ECG signs, clinical parameters, and left ventricular function. Fifteen patients with angiographically proven CHD were examined with 12-lead exercise ECG before, 2 h and 4 h after the first dose and after 10 days of therapy with 60 mg IS-5-MN (Coleb-Duriles) once daily. After 7 days, three radionuclide ventriculographies were performed: control, 2 h after nitrate and 2 h after 75 mg gallopamil. Plasma concentrations of IS-5-MN were measured before every exercise test. The results showed a reduction of total ST-segment depression from 0.59 mV to 0.29 mV after 2 h (NS) and 4 h (P less than 0.05) on the 1st day and from 0.48 mV to 0.32 mV (P less than 0.05) and 0.31 mV (NS) after 10 days. The severity of angina pectoris was diminished by about 50%. The effect on exercise duration and time to ST-segment depression by more than 0.1 mV remained unchanged after 10 days, whereas the effect on blood pressure, heart rate and time to onset of angina was attenuated. The mean decrease in ejection fraction (EF) from rest to exercise was reduced from--5.9% to -1.9% (P less than 0.05) after nitrate, while an increase of +1.4% was seen after gallopamil (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Sports and Performance Medicine, University of Ulm, Federal Republic of Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stauch
authors.forename: G
authors.initials: G
authors.lastname: Grossmann
authors.forename: D
authors.initials: D
authors.lastname: Wanjura
authors.forename: W E
authors.initials: WE
authors.lastname: Adam
mesh_terms: D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005711:Gallopamil / Q000097:blood / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D015635:Radionuclide Ventriculography / Q000187:drug effects
chemical_list: D003692:Delayed-Action Preparations; D005711:Gallopamil; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate