PDE5 Inhibitors

Sildenafil, tadalafil, vardenafil and avanafil block phosphodiesterase type 5, the enzyme that ends the nitric-oxide signal in vascular smooth muscle. Blocking it does not create that signal, it sustains one — so the class is a vasodilator waiting for something to dilate with, and the interaction below is a mechanism rather than a coincidence.

Alkyl nitrites donate nitric oxide directly. Taken with a PDE5 inhibitor the two work the same pathway from both ends, and blood pressure can fall further than it can be brought back from; medical nitrates do the same thing. Poppers are filed under Inhalants, and this is the pairing in this tree most likely to be met on one night. The window is not an evening for every member — tadalafil's outlasts the others by a long way. All four are CYP3A4 substrates, so an azole raises them.