Advances in therapy
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Advances in therapy · Sep 2009
ReviewPhosphodiesterase type 5 inhibitors in pulmonary arterial hypertension.
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. ⋯ 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.