[Evaluation of tolerance during intravenous administration of low dose of isosorbide dinitrate in the treatment of unstable angina]

Abstract

The eventuality of tolerance was assessed in 19 patients with unstable angina treated by continuous intravenous infusion of 50 micrograms/min of isosorbide trinitrate (ISDN) in association with heparin and betablocker therapy. The tolerance phenomenon was evaluated by the hypotension produced by the ISDN infusion and by the amplitude of fall in blood pressure produced by an intravenous bolus of 1 mg of glyceryl trinitrate (GTN) according to the principle of crossed tolerance to the two nitrate derivatives. Under these conditions of administration, the authors observed partial attenuation of the blood pressure response to continuous ISDN infusion and absence of cross tolerance between ISDN and intravenous GTN. The co-prescription of intravenous N-acetylcysteine at a dosage of 10 g/24 hours in 10 of the 19 patients did not affect the blood pressure or the response to the GTN bolus compared with the 9 other patients who had received placebo after double-blind randomisation. The results of this study do not indicate if the maintenance of vascular sensitivity to nitrate derivatives at least for 72 hours, was related to the choice of a relatively low dose and/or the use of ISDN rather than another nitrate derivative, in particular glyceryl trinitrate. The use of intravenous ISDN at a low dose over a 3 day period in the usual conditions of prescription for unstable angina does not seem to induce a quantitatively significant phenomenon of tolerance.