can be avoided in most patients if there is a nitrate- free interval of 10-12 hours per day.
may be the result of depletion of intracellular suphydryl groups which prevents further nitrate metabolism and nitric oxide release.
reversed within 18 hours of stopping nitrates.
if tolerance is supected in the case of modified isosorbide dinitrate (and conventional preparations of isosorbide mononitrate) then the second of two daily doses can be given after about 8 hours rather than after 12 hours.
there is no relationship to tolerance to adverse and therapeutic effects.
toleance may develop in less than 48 hours after the initiation of treatment with nitrates.
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