title: [Controlled clinical studies of tolerance development and dosing problems in nitrate therapy].
abstract: The phenomenon of development of tolerance to nitroglycerine as well as avoidance of this through a nitrate-free interval was known 100 years ago. Concerning the haemodynamic and anti-ischaemic effect of organic nitrates in therapy, the development of a tolerance is a clinical problem that is much discussed. Conducive to tolerance are obviously continuous application, short dosing intervals and high-dosage level so that an anti-ischaemic protection or rather, for heart insufficiency a haemodynamic relief, cannot be achieved by using organic nitrates around the clock. On the contrary, keeping a nitrate-free interval of 12 to 18 hours allows proof of the effect of at least 12 hours under IS-5-MN as is also the case under s.r. ISDN or 8 hours under nitroglycerine-patches. In this case, a lack of anti-ischaemic protection in the interval, particularly in the early morning hours, has to be accepted.
authors.forename: U
authors.initials: U
authors.lastname: Abshagen
mesh_terms: D000787:Angina Pectoris / Q000188:drug therapy*; D003327:Coronary Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009566:Nitrates / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D009566:Nitrates; D014665:Vasodilator Agents
vernacular_title: Kontrollierte klinische Studien zur Toleranzentwicklung und Dosierungsprobleme der Nitrattherapie.