Document Detail

Effects of diuretic therapy on the development of tolerance to nitroglycerin and exercise capacity in patients with chronic stable angina.
MedLine Citation:
PMID:  8640997     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Therapy with diuretics has been reported to prevent the development of nitrate tolerance. Importantly, diuretics may have independent antianginal effects through their effects on intravascular volume. The present investigation was designed to determine whether diuretic therapy could prevent the development of tolerance to continuous transdermal nitroglycerin. The study was also designed to examine whether diuretic therapy has an independent antianginal effect. METHODS AND RESULTS: Twelve patients with chronic stable angina were studied in a randomized, double-blind, crossover trial. Patients received diuretic (hydrochlorothiazide plus amiloride) or placebo for 14 to 20 days. During each double-blind treatment period, patients underwent treadmill exercise testing on three separate occasions. The first exercise testing was performed after 7 to 10 days of single-blind, placebo transdermal nitroglycerin therapy. Subsequently, exercise testing was repeated on the first day of active transdermal nitroglycerin therapy and following 7 to 10 days of continuous transdermal nitroglycerin application. Therapy with a diuretic was associated with an increase in exercise capacity but had no effect on nitroglycerin tolerance. During therapy with placebo transdermal nitroglycerin, diuretic therapy caused an increase in treadmill walking time to the development of moderate angina compared with placebo (371 +/- 26 versus 288 +/- 16 seconds, diuretic versus placebo, P < .01). Similar results were obtained during both acute and sustained nitroglycerin therapy. CONCLUSIONS: The results of this study demonstrate that therapy with a diuretic has no effect on the development of tolerance to continuous transdermal nitroglycerin. Interestingly, diuretic therapy itself has important antianginal effects and improves exercise capacity in patients with stable angina.
J D Parker; A B Parker; B Farrell; J O Parker
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  93     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-07-15     Completed Date:  1996-07-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  691-6     Citation Subset:  AIM; IM    
Department of Medicine, Queen's University, Kingston (Ontario) General Hospital, Canada.
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MeSH Terms
Administration, Cutaneous
Amiloride / administration & dosage,  therapeutic use*
Angina Pectoris / drug therapy*,  physiopathology
Blood Pressure / drug effects
Chronic Disease
Cross-Over Studies
Double-Blind Method
Drug Therapy, Combination
Drug Tolerance
Exercise Test
Heart Rate / drug effects
Hydrochlorothiazide / administration & dosage,  therapeutic use*
Middle Aged
Nitroglycerin / administration & dosage,  therapeutic use*
Reg. No./Substance:
2609-46-3/Amiloride; 55-63-0/Nitroglycerin; 58-93-5/Hydrochlorothiazide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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