PDE5 inhibitors
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PDE5 inhibitors
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PDE5 inhibitors
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Erectile dysfunction p. 590
sildenafil p. 711
Sildenafil p. 675, 681
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Transcript
Content Reviewers
Yifan Xiao, MDPhosphodiesterase 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.
Summary
PDE5 (phosphodiesterase type 5) inhibitors are a class of drugs that are used to treat erectile dysfunction and pulmonary hypertension. These drugs work by inhibiting the activity of the enzyme phosphodiesterase type 5 (PDE5), which is responsible for breaking down cyclic guanosine monophosphate (cGMP) in the body. By inhibiting PDE5, these drugs increase the levels of cGMP, which relaxes the smooth muscle tissue in the blood vessels of the penis and lungs, leading to an increase in blood flow. Examples of PDE5 inhibitors include drugs like sildenafil, vardenafil, and tadalafil.
Sources
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Effect of daily tadalafil on reported outcomes in patients with erectile dysfunction and depressive symptoms" Medicine (2020)
- "To evaluate the efficacy and safety of different kinds of PDE5-Is with tamsulosin as a medical therapy for LUTS secondary to benign prostatic hyperplasia" Medicine (2020)
- "Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis" International Urology and Nephrology (2017)
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