Document Detail


Prostanoids for pulmonary arterial hypertension.
MedLine Citation:
PMID:  14720012     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary arterial hypertension (PAH) is a severe condition that markedly reduces exercise capacity and survival in the affected patient population. PAH includes primary pulmonary hypertension (PPH) and pulmonary hypertension associated with collagen vascular diseases, congenital systemic-to-pulmonary shunts, portal hypertension and HIV infection. All these conditions share virtually identical obstructive pathologic changes of the pulmonary microcirculation and probably similar pathobiologic processes. The pathophysiology is characterized by a progressive increase in pulmonary vascular resistance, leading to right ventricular failure and death. Prostacyclin is an endogenous substance that is produced by vascular endothelial cells and induces vasodilatation, inhibition of platelet activity, and antiproliferative effects. A dysregulation of prostacyclin metabolic pathways has been shown in patients with PAH and this represents the rationale for the exogenous therapeutic administration of this substance. The clinical use of prostacyclin in patients with PAH has been made possible by the synthesis of stable analogs that possess different pharmacokinetic properties but share similar pharmacodynamic effects. Experience in humans has been initially collected with epoprostenol, which is a synthetic salt of prostacyclin. Epoprostenol has a short half-life in the circulation and requires continuous administration by the intravenous route by means of infusion pumps and permanent tunnelized catheters. In addition, epoprostenol is unstable at room temperature, and the complex delivery system required is associated with several adverse effects and potentially serious complications. For these reasons, alternatives to intravenous epoprostenol have been sought and this has led to the development of analogs that can be administered subcutaneously (treprostinil), orally (beraprost sodium) or by inhalation (iloprost). Three unblinded clinical trials and several uncontrolled trials have shown that treatment with epoprostenol improved symptoms and exercise capacity in New York Heart Association (NYHA) class III and IV PAH patients and also survival in patients with PPH. Subcutaneous treprostinil improved symptoms, exercise, hemodynamics and clinical events in the largest clinical trial ever performed in PAH, but local infusion site reactions limited efficacy in a proportion of patients. Oral beraprost sodium improved exercise capacity only in patients with PPH and is the only prostacyclin analog that has also been tested in NYHA class II patients. Inhaled iloprost has improved symptoms, exercise capacity and clinical events in patients with PAH and inoperable chronic thromboembolic pulmonary hypertension. The favorable effects of prostanoids observed in all studies coupled with different profiles of adverse events and tolerability for each prostacyclin analog allow the unique opportunity to select the most appropriate compound for the individual patient with PAH.
Authors:
Nazzareno Galiè; Alessandra Manes; Angelo Branzi
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  American journal of respiratory medicine : drugs, devices, and other interventions     Volume:  2     ISSN:  1175-6365     ISO Abbreviation:  Am J Respir Med     Publication Date:  2003  
Date Detail:
Created Date:  2004-01-14     Completed Date:  2004-01-30     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  101132974     Medline TA:  Am J Respir Med     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  123-37     Citation Subset:  IM    
Affiliation:
Institute of Cardiology, University of Bologna, Bologna, Italy. n.galie@bo.nettuno.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Age Distribution
Aged
Cause of Death*
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Hypertension, Pulmonary / diagnosis,  drug therapy*,  mortality*
Male
Middle Aged
Prognosis
Prostaglandins / administration & dosage*,  adverse effects
Randomized Controlled Trials as Topic
Risk Assessment
Severity of Illness Index
Sex Distribution
Survival Analysis
Treatment Outcome
Chemical
Reg. No./Substance:
0/Prostaglandins

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


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