Therapeutic strategies for optimizing PDE-5 inhibitor therapy in patients with erectile dysfunction considered difficult or challenging to treat

International Journal of Impotence Research
I Sáenz de Tejada

Abstract

Phosphodiesterase 5 (PDE5) inhibitors prevent the normal hydrolysis of cGMP. As the resulting cGMP accumulation facilitates penile smooth muscle relaxation, PDE5 inhibitors can partially reverse deficiencies in the nitric oxide (NO)/cGMP pathway to treat erectile dysfunction (ED). However, approximately 30-40% of men with ED do not respond to drug therapy. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5 inhibitors. Decreased expression or activity of neuronal or endothelial NO synthase (NOS), impaired NO release, or NO destruction will preclude sufficient cGMP formation to permit PDE5 inhibitor efficacy. This article discusses the possible reasons for unresponsiveness and strategies to overcome it. Therapeutic approaches proposed to increase available NO in penile tissue include facilitating NO release by using alpha-2 antagonists, enhancing NO synthesis by providing more substrate for the reaction, and using antioxidants to inhibit NO breakdown by reactive oxygen species.

References

Sep 1, 1997·The Journal of Urology·J A MoodyN F Gonzalez-Cadavid
Sep 21, 2000·Kidney International. Supplement·T NishikawaM Brownlee
Mar 14, 2002·International Journal of Impotence Research·I Saenz de TejadaE Bischoff
Dec 31, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Trinity J BivalacquaHunter C Champion

❮ Previous
Next ❯

Citations

May 21, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Jaqueline J MunizJose E Tanus-Santos
Jul 1, 2006·Journal of Sex & Marital Therapy·Jennifer L BarskyRaymond C Rosen
Dec 24, 2005·Asian Journal of Andrology·Louis J G Gooren, Farid Saad
Sep 20, 2012·The Journal of Sexual Medicine·George F LaskerPhilip J Kadowitz
May 3, 2012·The Journal of Sexual Medicine·Olav SchjørringUlf Simonsen
May 21, 2014·The Journal of Sexual Medicine·Bart PauwelsJohan Van de Voorde
Jan 21, 2006·The Journal of Sexual Medicine·Ronald W LewisSanjeev Ahuja
Dec 16, 2006·The Journal of Clinical Hypertension·Arthur L Burnett
May 20, 2011·BJU International·Consuelo Valles-AntuñaFernando Fernandez-Gonzalez
Sep 5, 2006·European Urology·Konstantinos Hatzimouratidis, Dimitrios Hatzichristou
Sep 18, 2013·The World Journal of Men's Health·Akira Tsujimura
Dec 14, 2019·Diabetes/metabolism Research and Reviews·Shaishav DhageRayaz A Malik
Apr 25, 2020·Current Pharmaceutical Design·Ecem Kaya-Sezginer, Serap Gur

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Urology
Drogo K MontagueErectile Dysfunction Guideline Update Panel
Endocrinology and Metabolism Clinics of North America
William O BrantT Lue
© 2022 Meta ULC. All rights reserved