Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary arterial hypertension (PAH) is a severe vasculopathy, which is characterised by progressive narrowing and obliteration of the pulmonary arterioles and increased endothelin-1 levels. The increase of vascular resistance in the lung vessels leads to chronic pressure overload and to right heart failure, if untreated. PAH often occurs in association with rheumatic-inflammatory diseases (e.g., in 15% of patients with systemic sclerosis (SSc), especially in the limited form or in CREST patients) and determines their prognosis: in advanced stages, untreated patients die within a short period. Therefore all SSc patients, particularly the newly diagnosed ones, should be screened for PAH with echocardiography. If PAH is suspected, a right heart catheter should be performed, and if PAH is confirmed, adequate treatment should be initiated. While few years ago lung transplantation was the only option for patients with severe PAH, in recent years enormous progress was seen in drug treatment. Today prostanoids (Ventavis) and the endothelin receptor antagonist bosentan (Tracleer) are available for patients with PAH in WHO/NYHA stage III: they have substantially improved the prognosis of PAH in the last years. Since few months, also the phosphodiesterase inhibitor sildenafil (Revatio) is available. The combination of drugs with different mode of action will likely further improve the prognosis of PAH patients.
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PMID:[Pulmonary arterial hypertension in collagenoses: clinical features, epidemiology, pathogenesis, diagnosis and treatment]. 1680 98

Pulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in long-term combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome. Traces of the acute hemodynamic effects of beraprost (20 microg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours. After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 microg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome.
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PMID:Combination therapy with oral sildenafil and beraprost for pulmonary arterial hypertension associated with CREST syndrome. 1759 7