title: How long can an escalation of dose override tolerance to the hypotensive efficacy of nitroglycerin infusion in coronary care patients.
abstract: Tolerance to nitroglycerin infusion (NG) can be overridden by dose escalation. The aim of this study was to define for how long it can be done for hypotensive efficacy of NG, in a coronary care setting. A prospective trial with an intra-individual therapeutic comparison was performed in 60 patients with acute myocardial infarction or unstable angina. Initial efficacy of NG was confirmed by a 10% blood pressure decrease (measured by cuff). Seventy-two-hour NG infusion was interrupted, for 30 minutes, every 12 hours. If blood pressure increased by 10% after infusion interruption, the infusion was continued at the previous rate. If blood pressure did not increase (detected tolerance--weakened efficacy of NG), the dose was increased until pressure decreased by 10% and the infusion was continued at the new dose. Failure to achieve hypotensive response, despite a 5-fold dose increase, indicated onset of resistance--completely lost hypotensive efficacy of NG. The majority of patients (49 out of 55) who developed tolerance, developed it during the first 36 hours, while the majority of those who developed resistance (33 out of 40), developed it within 60 hours of the infusion. Tolerance was overridden by dose escalation in 41 out of 55 patients, which was repeated in 31 patients. Complete restoration of NG action was possible over 24 hours in half the patients, and over 48 hours in one third of the patients. Three out of 34 patients who developed tolerance before the 13th hour did not develop resistance during the following 60 hours of dose up-titration. The conclusion is that tolerance to NG can be overridden by dose escalation in the majority of patients for a significant period of time, which is useful in clinical practice.
authors.affiliation: Department of Cardiology, Krapinske Toplice Hospital, Croatia.
authors.forename: G
authors.initials: G
authors.lastname: Milicevic
authors.forename: V
authors.initials: V
authors.lastname: Goldner
authors.forename: B
authors.initials: B
authors.lastname: Vrhovac
authors.forename: H
authors.initials: H
authors.lastname: Prpic
authors.forename: D
authors.initials: D
authors.lastname: Planinc
authors.forename: M
authors.initials: M
authors.lastname: Majsec
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy; D003327:Coronary Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D005996:Nitroglycerin / Q000627:therapeutic use*; D010352:Patient Dropouts; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D005996:Nitroglycerin