title: [The problem of tolerance to nitrates and the means to resolve it in patients with exertional stenocardia].
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.
authors.forename: V I
authors.initials: VI
authors.lastname: Metelitsa
authors.forename: S Iu
authors.initials: SIu
authors.lastname: Martsevich
authors.forename: E V
authors.initials: EV
authors.lastname: Kokurina
authors.forename: M P
authors.initials: MP
authors.lastname: Kozyreva
authors.forename: E V
authors.initials: EV
authors.lastname: Bochkareva
mesh_terms: D000787:Angina Pectoris / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D004361:Drug Tolerance; D006801:Humans; D009566:Nitrates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005082:Physical Exertion / Q000187:drug effects*
chemical_list: D003692:Delayed-Action Preparations; D009566:Nitrates
vernacular_title: Problema tolerantnosti k nitratam i puti ee resheniia u bol'nykh stenokardieĭ napriazheniia.