Tolerance development during isosorbide dinitrate treatment: can it be circumvented?
Based on studies carried out according to randomized, double-blind, crossover, placebo-controlled protocols, analysis was performed to assess the antiischemic effects of (a) 40 mg ISDN, both after acute administration and during long-term treatment with four doses daily, (b) treatment with 20 mg ISDN twice daily (at 8 a.m. and 1 p.m.), and (c) 0.8 mg sublingually administered NTG during treatment with 40 mg ISDN four times daily. After acute administration of 40 mg ISDN there was a reduction in ST-segment depression from 2.05 to 0.18 mm (p less than 0.01). During chronic treatment, statistically-significant changes were no longer detectable. Sublingual administration of 0.8 mg NTG led to a reduction of ST-segment depression during the acute phase of ISDN from 1.20 to 0.15 mm (-87%; p less than 0.01) and during chronic treatment from 1.90 to 0.90 mm (-53%; p less than 0.01). Accordingly, as compared with changes induced in the acute and placebo phases, the effectiveness of NTG during chronic ISDN treatment was diminished. After acute administration of 20 mg ISDN, ST-segment depression was reduced from 2.15 to 0.40 mm (p less than 0.01) and to a comparable degree during long-term twice-daily treatment, from 2.25 to 0.40 mm (p less than 0.01). There was a significant reduction in the rate of anginal attacks and nitrate consumption. Thus, with respect to the anti-ischemic effectiveness of ISDN, tolerance development is incurred during repeated administration. Concomitantly, the effectiveness of NTG is not essentially negated, but rather diminished.(ABSTRACT TRUNCATED AT 250 WORDS)
D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004361:Drug Tolerance; D004562:Electrocardiography; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000627:therapeutic use; D011897:Random Allocation
D005996:Nitroglycerin; D007548:Isosorbide Dinitrate