title: [Development of nitrate tolerance in individual patients with stable angina pectoris in various phases of therapy with oral isosorbide dinitrate].
abstract: The aim of the work was an individual assessment of the effect on coronary reserve exerted by the widely used drug from the group of nitrates--isosorbide dinitrate (ISDN) in conventional and slow-release (SR) presentations, in various doses. The patients--38 males with stable coronary disease were given orally, by randomised double blind method, conventional isosorbide dinitrate (ISDN) in 10 and 20 mg doses, and slow-release isosorbide dinitrate in 20 mg SR, 40 mg SR, 80 mg SR and 120 mg SR doses, or placebo for the first time and for 7 days: four times daily, three times daily (with a 12-hour break), twice daily (with an 18-hour break) and once daily. In each of the therapeutic methods, walking times were analysed during exercise test six hours following drug administration, that is total time (TT), time to angina (TA) and time to ischaemia (TI). A prolongation by > or = 20% of walking times after ISDN administration as compared to placebo in > 50% of patients was accepted as significant improvement. Six hours after the first administration, a significant improvement of TT, TA and TI as compared to placebo was observed in the case of ISDN 20 mg, 40 mg SR, 80 mg SR and 120 mg SR. After administration of the drugs four times daily no significant improvement was observed after any dose. After administration of the drugs thrice daily, significant improvement was found in the case of TA (80 mg SR) and TI (20 mg SR, 40 mg SR and 120 mg SR), after twice daily administration--in the case of TI (40 mg SR and 80 mg SR) and after once daily administration--in the case of TT (80 mg SR), TA (120 mg SR) and TI (40 mg SR, 80 mg SR and 120 mg SR). In > 50% of patients, the coronary activity of ISDN in higher doses persists for six hours in the case of the first time administration; continuous therapy leads to tolerance development and intermittent therapy makes possible to avoid it. Tolerance does not depend on patients' sensitivity to nitrates.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000787:Angina Pectoris / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005080:Exercise Test; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate
vernacular_title: Wystepowanie tolerancji azotanów u poszczególnych chorych ze stabilna dławica piersiowa w róznych odmianach leczenia doustnym dwuazotanem izosorbitolu.