Document Detail


Prostanoid therapy for pulmonary arterial hypertension.
MedLine Citation:
PMID:  15194179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prostanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients had less disease progression at six months and confirmed the results of the previous trial. However, this improvement was no longer present at 9 or 12 months. In conclusion, though treatment with prostanoids is complicated by their generally short half-lives and complicated drug delivery systems, they continue to play an important role in the treatment of PAH.
Authors:
David B Badesch; Vallerie V McLaughlin; Marion Delcroix; Carmine Dario Vizza; Horst Olschewski; Olivier Sitbon; Robyn J Barst
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  43     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-14     Completed Date:  2004-07-27     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  56S-61S     Citation Subset:  AIM; IM    
Affiliation:
University of Colorado Health Sciences Center, Denver, Colorado, USA. David.Badesch@UCHSC.edu
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MeSH Terms
Descriptor/Qualifier:
Antihypertensive Agents / therapeutic use
Epoprostenol / analogs & derivatives*,  therapeutic use
Humans
Hypertension, Pulmonary / drug therapy*
Iloprost / therapeutic use
Prostaglandins / therapeutic use*
Pulmonary Artery / drug effects*,  pathology*
Vasodilator Agents / therapeutic use
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Prostaglandins; 0/Vasodilator Agents; 0/treprostinil; 35121-78-9/Epoprostenol; 78919-13-8/Iloprost

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


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