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Phosphodiesterase Type 5 (PDE5) Inhibitors.


LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
2017 Aug 2.


The phosphodiesterase type 5 (PDE5) inhibitors cause vasodilation in the penis and lung by blocking the breakdown of cyclic guanosine monophosphate (cGMP) which results in prolongation of the action of mediators of vasodilation including nitric oxide (NO). The type-5 phosphodiesterases are isoforms of this enzyme that are found primarily in the corpus cavernosum of penis and vasculature of the lung. For these reasons, the two major actions of the PDE5 inhibitors are to prolong penile erection and decrease pulmonary vascular pressure. They have little effect on the systemic vasculature. Four PDE5 inhibitors are currently approved and in use for treatment of erectile dysfunction including sildenafil (Viagra: 1998), tadalafil (Cialis: 2003), vardenafil (Levitra: 2003) and avanafil (Stendra: 2012), all of which are recommended to be taken orally one-half to 4 hours before sexual intercourse. Typically, no more than once daily use is recommended. The PDE5 inhibitors are not approved for use in women. Sildenafil is approved for use in pulmonary hypertension where two to three times daily chronic dosing is used. Its safety and efficacy are still under experimental evaluation, particularly in patients with end stage liver disease (hepato-pulmonary syndrome) and in patients with sickle cell anemia with pulmonary hypertension. Rare single case reports of acute liver injury have been reported with use of PDE5 inhibitors, mostly with sildenafil, most likely becausethe others have been available for a shorter time and are less commonly used. The four agents share a similar mechanism of action, but have structural differences, and it is not clear whether liver injury is a class effect or specific to sildenafil. Chronic sildenafil use has not been associated with serum aminotransferase elevations.

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