Nitrate cross-tolerance: effect of sublingual isosorbide dinitrate and nitroglycerin during sustained nitrate therapy.
In a randomized, single-blind, crossover study, 10 patients with stable, exercise-induced angina pectoris were studied during sustained therapy with oral isosorbide dinitrate (ISDN). Circulatory changes and exercise performance were evaluated before and 6 hours after therapy with oral ISDN. One-half hour after this therapy, sublingual ISDN or nitroglycerin (NTG) was administered and exercise testing repeated. Treadmill walking time 6 hours after oral ISDN was similar to the control value. Subsequent administration of sublingual ISDN improved walking time from 429 +/- 156 to 513 +/- 166 seconds (p less than 0.005), whereas after NTG improved from 411 +/- 159 to 480 +/- 158 second (p less than 0.005). The improvement in walking time with ISDN (23%) and NTG (18%) and the absolute walking times were not different. The standing systolic blood pressure decreased from 124 +/- 23 to 112 +/- 22 mm Hg (p less than 0.02) after therapy with sublingual ISDN and 122 +/- 23 to 110 +/- 24 mm Hg (p less than 0.005) after administration of NTG. This study demonstrates that (1) during sustained ISDN therapy, walking time returns to control values by 6 hours; (2) administration of either sublingual ISDN or NTG results in significant circulatory changes and improvement in walking time; and (3) the changes in circulatory and exercise variables after administration of NTG in patients taking sustained ISDN therapy cannot be taken as evidence of an absence of cross-tolerance between these agents.
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009060:Mouth Floor; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000627:therapeutic use; D011897:Random Allocation
D005996:Nitroglycerin; D007548:Isosorbide Dinitrate