Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Olschewski, H; Rose, F; Schermuly, R; Ghofrani, HA; Enke, B; Olschewski, A; Seeger, W.
Prostacyclin and its analogues in the treatment of pulmonary hypertension.
Pharmacol Ther. 2004; 102(2):139-153
Doi: 10.1016/j.pharmthera.2004.01.003
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PubMed
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- Führende Autor*innen der Med Uni Graz
- Olschewski Horst
- Co-Autor*innen der Med Uni Graz
- Olschewski Andrea
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- Abstract:
- Prostacyclin and its analogues (prostanoids) are potent vasodilators and possess antithrombotic and antiproliferative properties. All of these properties help to antagonize the pathological changes that take place in the small pulmonary arteries of patients with pulmonary hypertension. Indeed, several prostanoids have been shown to be efficacious to treat pulmonary hypertension, while the main mechanism underlying the beneficial effects remains unknown. There are indications of beneficial combination effects of prostaglandins and phosphodiesterase inhibitors and endothelin receptor antagonists. This speaks in favor of combination therapies for pulmonary hypertension in the future. The mode of application of prostanoids used in randomized controlled studies has been quite variable: continuous i.v. infusion of prostacyclin, continuous s.c. infusion of treprostinil, p.o. application of beraprost, and inhaled application of iloprost. In addition, the applied doses were quite different, ranging from 0.25 ng/kg/min for inhaled iloprost to 30-50 ng/kg/min for i.v. prostacyclin. While the principal pharmacological properties of all prostanoids are very similar due to a main action on IP receptors, there are considerable differences in pharmacokinetics and metabolism, with half-lives of 2 min for prostacyclin and about 34 min for treprostinil for i.v. infused drugs and half-lives of about 85 min for s.c. infused treprostinil. In addition, the adverse effects largely depend on the doses used and the mode of application, although there is great variability between subjects. It remains to be determined which patients will profit most from which substance (or combination) and mode of application.
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