20.2 : 肺高血圧症の治療：ホスホジエステラーゼ阻害剤

Phosphodiesterase inhibitors treat pulmonary arterial hypertension or PAH by inhibiting the activity of the phosphodiesterase enzyme.

Phosphodiesterase 5 or PDE5 is prevalent in the smooth muscle cells of the pulmonary artery. It cleaves and degrades cyclic nucleotide, cGMP into its monophosphate, 5'-GMP.

Sildenafil, a competitive and selective inhibitor of PDE5, effectively mimics the purine ring of cGMP, preventing its hydrolysis.

This action elevates cellular cGMP levels,  enhancing signaling through the cGMP-PKG pathway.

Administered orally, sildenafil rapidly reaches peak plasma concentration within an hour.

It is metabolized by hepatic enzymes, CYP3A, and CYP2C9.

Both sildenafil and its active metabolite have half-lives of approximately 4 hours and are primarily excreted through feces.

Common side effects of sildenafil include headaches and flushing. It can also cause transient blue-green tinting of vision.

Tadalafil, another PDE5 inhibitor, differs structurally from sildenafil and has a longer half-life.