 Sildenafil, vardenafil, tadalafil, and avanafil are PDE5 inhibitors that are significantly more potent and selective than zaprinast and other early PDE5 inhibitors.PDE5 is an enzyme that accepts cGMP and breaks it down.Sildenafil, vardenafil and tadalafil are inhibitors of this enzyme, which bind to the catalytic site of PDE5.