title: N-acetylcysteine fails to attenuate haemodynamic tolerance to glyceryl trinitrate in healthy volunteers.
abstract: 1. The effects of chronic dosing with N-acetylcysteine (NAC), on nitrate-induced haemodynamic changes during the acute and chronic treatment of healthy volunteers with glyceryl trinitrate (GTN) patches (Transiderm nitro) has been investigated. 2. Seven volunteers were treated in a double-blind randomised crossover manner for two periods of 4 days with 20 mg of transdermal GTN/24 h together with NAC (200 mg three times daily) or matching placebo. There was a washout period of greater than 3 days between treatment periods. 3. Haemodynamic measurements (blood pressure (BP); heart rate (HR] at rest and following maximal treadmill exercise were performed before treatment and 4 h after starting treatment on days 1 and 4. 4. Significant haemodynamic changes as evidenced by a fall in BP and rise in HR, were seen on day 1 in both the NAC and placebo phases. By day 4 the haemodynamic changes had returned towards the pre-treatment values during both the NAC and placebo phases suggesting the development of tolerance in both treatment groups. 5. These findings suggest that concurrent administration of NAC fails to prevent the development of tolerance to GTN.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff.
authors.forename: J C
authors.initials: JC
authors.lastname: Hogan
authors.forename: M J
authors.initials: MJ
authors.lastname: Lewis
authors.forename: A H
authors.initials: AH
authors.lastname: Henderson
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004361:Drug Tolerance; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000097:blood / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic
chemical_list: D005996:Nitroglycerin; D000111:Acetylcysteine