Phosphodiesterase type 5, or PDE5, inhibitors are a class of medications used to treat erectile dysfunction and pulmonary hypertension.
As their name implies, they inhibit the PDE5 enzyme in endothelial cells, which allows for smooth muscle relaxation and thus, promotes blood vessel dilation.
They include sildenafil, vardenafil, and tadalafil.
Alright, first, let’s focus on the structure of blood vessels.
Blood vessels have three layers, also called “tunics,” or coverings, that surround the vessel lumen, the hollow part of the vessel that contains the blood.
The innermost tunic is the tunica intima, which includes the endothelial cells; the next one is the tunica media, or middle tunic, which is mostly made of smooth muscle cells and sheets of elastin protein; and finally, there’s the tunica externa, or outside tunic, which is made up of loosely woven fibers of collagen.
Moreover, the tunica media can contract, causing vasoconstriction, where the lumen gets a lot smaller; or it can relax, or vasodilate, causing the lumen’s diameter to increase, allowing for more blood flow.
Now, within endothelial cells of the tunica intima, there’s an enzyme called nitric oxide synthase, which uses the amino acid L-arginine and molecular oxygen to synthesize nitric oxide or NO for short.
Once synthesized, nitric oxide diffuses to adjacent smooth muscle cells in the tunica media, where it binds and activates an enzyme called guanylyl cyclase.
This enzyme converts guanosine triphosphate, GTP, into cyclic guanosine monophosphate, cGMP, which is a second messenger that induces relaxation of smooth muscle cells in vessel walls.
Alright, now the cGMP-specific phosphodiesterase type 5, or PDE5, is an enzyme found in various tissues, mainly in the corpus cavernosum of the penis and the retina.
It’s also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle.
Recently it’s been discovered to play a role in the cardiovascular system. PDE5 normally breaks down cGMP causing its inactivation.
Okay, now PDE5 inhibitors include sildenafil, vardenafil, and tadalafil.
These medications inhibit the PDE5 enzyme in endothelial cells which normally breaks down cGMP.
Increased cGMP increases the smooth muscle relaxation in response to nitric oxide.
As a result there is an increase in blood flow in the corpus cavernosum of the penis, and a reduction in pulmonary vascular resistance.
Now, PDE5 inhibitors are used in the treatment of erectile dysfunction, which is the inability to develop or maintain an erection due to psychological or organic causes.
It does this by enhancing the erectile response to sexual stimulation.
PDE5 inhibitors also treat pulmonary hypertension, which refers to increased blood pressure in the pulmonary circulation, more specifically, a mean pulmonary arterial pressure that is greater than 25 millimeters of mercury.
Peak plasma concentration of sildenafil occurs approximately 30 minutes to two hours after its given orally and can be delayed by eating.