Nitrate tolerance: hemodynamic effects of intravenous isosorbide dinitrate after sustained oral isosorbide dinitrate administration

Abstract

To determine whether hemodynamic effects of isosorbide dinitrate (ISDN) diminish and disappear during sustained administration, nine patients with recent myocardial infarction received 10 mg of ISDN intravenously before and 1, 4, 12, 24, and 48 weeks after sustained oral administration of 20 mg of the slow-release form of ISDN four times daily. Blood pressure always decreased after intravenous ISDN; the decrease tended to be diminished when preceded by oral ISDN, but no further attenuation in blood pressure was noted. The decrease in blood pressure was associated with consistent and nonsignificant increases in heart rate after intravenous ISDN. Plasma ISDN levels were not affected by prior oral ISDN. Plasma isosorbide 2-mononitrate and isosorbide 5-mononitrate levels were consistently higher when preceded by oral ISDN. The results suggest that the hemodynamic and metabolic properties of ISDN are preserved even after sustained therapy.