Document Detail

Challenges with Nitrate Therapy and Nitrate Tolerance: Prevalence, Prevention, and Clinical Relevance.
MedLine Citation:
PMID:  24664980     Owner:  NLM     Status:  Publisher    
Nitrate therapy has been an effective treatment for ischemic heart disease for over 100 years. The anti-ischemic and exercise-promoting benefits of sublingually administered nitrates are well established. Nitroglycerin is indicated for the relief of an established attack of angina and for prophylactic use, but its effects are short lived. In an effort to increase the duration of beneficial effects, long-acting orally administered and topical applications of nitrates have been developed; however, following their continued or frequent daily use, patients soon develop tolerance to these long-acting nitrate preparations. Once tolerance develops, patients begin losing the protective effects of the long-acting nitrate therapy. By providing a nitrate-free interval, or declining nitrate levels at night, one can overcome or reduce the development of tolerance, but cannot provide 24-h anti-anginal and anti-ischemic protection. In addition, patients may be vulnerable to occurrence of rebound angina and myocardial ischemia during periods of absent nitrate levels at night and early hours of the morning, and worsening of exercise capacity prior to the morning dose of the medication. This has been a concern with nitroglycerin patches but not with oral formulations of isosorbide-5 mononitrates, and has not been adequately studied with isosorbide dinitrate. This paper describes problems associated with nitrate tolerance, reviews mechanisms by which nitrate tolerance and loss of efficacy develop, and presents strategies to avoid nitrate tolerance and maintain efficacy when using long-acting nitrate formulations.
Udho Thadani
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-25
Journal Detail:
Title:  American journal of cardiovascular drugs : drugs, devices, and other interventions     Volume:  -     ISSN:  1179-187X     ISO Abbreviation:  Am J Cardiovasc Drugs     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-3-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100967755     Medline TA:  Am J Cardiovasc Drugs     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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