Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension
| العنوان: | Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension |
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| المؤلفون: | Gérald Simonneau, Laurent Savale, Olivier Sitbon, Delphine Natali, Marc Humbert, Xavier Jaïs, Laura C. Price, Marie-Camille Chaumais, David Montani |
| المصدر: | Advances in Therapy. 26:813-825 |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Phosphodiesterase Inhibitors, Sildenafil, Hypertension, Pulmonary, Vasodilation, Pharmacology, Piperazines, Sildenafil Citrate, Tadalafil, chemistry.chemical_compound, Vardenafil Dihydrochloride, Humans, Medicine, Pharmacology (medical), Sulfones, Cyclic guanosine monophosphate, Triazines, business.industry, Imidazoles, General Medicine, Phosphodiesterase 5 Inhibitors, medicine.disease, Bosentan, Erectile dysfunction, chemistry, Purines, Vardenafil, cGMP-specific phosphodiesterase type 5, Pulmonary Veno-Occlusive Disease, business, Algorithms, Carbolines, medicine.drug |
| الوصف: | Pulmonary arterial hypertension (PAH) is a rare disease characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary arterial resistance, right heart failure, and death. The pathogenesis of PAH is multifactorial, with endothelial cell dysfunction playing an integral role. This endothelial dysfunction is characterized by an overproduction of vasoconstrictors and proliferative factors, such as endothelin-1, and a reduction of vasodilators and antiproliferative factors, such prostacyclin and nitric oxide. Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. PDE-5 is abundantly expressed in lung tissue, and appears to be upregulated in PAH. Three oral PDE-5 inhibitors are available (sildenafil, tadalafil, and vardenafil) and are the recommended first-line treatment for erectile dysfunction. Experimental studies have shown the beneficial effects of PDE-5 inhibitors on pulmonary vascular remodeling and vasodilatation, justifying their investigation in PAH. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil, which are therefore currently the approved PDE-5 inhibitors in PAH treatment. Sildenafil and tadalafil significantly improve clinical status, exercise capacity, and hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor antagonists may be helpful in the management of PAH although further studies are needed in this area. The third PDE-5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are usually mild and transient and include headache, flushing, nasal congestion, digestive disorders, and myalgia. Mild and moderate renal or hepatic failure does not significantly affect the metabolism of PDE-5 inhibitors, whereas coadministration of bosentan decreases sildenafil and tadalafil plasma levels. Due to their clinical effectiveness, tolerance profile, and their oral administration, sildenafil and tadalafil are two of the recommended first-line therapies for PAH patients in World Health Organization functional classes II or III. |
| تدمد: | 1865-8652 0741-238X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8fa2faffb4f51b5796213664f58e555dTest https://doi.org/10.1007/s12325-009-0064-zTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....8fa2faffb4f51b5796213664f58e555d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18658652 0741238X |
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