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  • Title: [The problem of tolerance to nitrates and the means to resolve it in patients with exertional stenocardia].
    Author: Metelitsa VI, Martsevich SIu, Kokurina EV, Kozyreva MP, Bochkareva EV.
    Journal: Ter Arkh; 1993; 65(9):34-40. PubMed ID: 8303592.
    Abstract:
    The problem of nitrates tolerance and resistance has been studied for 10 years in a number of clinical pharmacological cross-over studies in patients with stable angina of effort by specially devised pharmacodynamic and pharmacokinetic methods. Both single doses in different medicinal forms and long-term course intake of nitrates were investigated. The results led the authors to the following conclusions: 1) tolerance to isosorbide dinitrate arises in 58% of the patients for 6-12 weeks under regular administration of the drug; 2) transdermal nitroglycerin (nitroderm) and in a less degree oral sustak under long-term treatment regimens become tolerable, whereas a buccal form (trinitrolong) secures a prolonged stable effect; 3) tolerance develops in 2-month administration of oral isosorbide-5-mononitrate; 4) donors of SH-group (methionine) and inhibitors of angiotensin-converting enzyme with SH-group and without it (captopril and perindopril, respectively) in single doses potentiate an antianginal effect of isosorbide dinitrate (even in initial resistance to nitrate), being ineffective in its absence; 5) molsidomine is promising in long-term regimens as an antianginal drug alternative to nitrates.
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