Current use of phosphodiesterase inhibitors in urology

Abstract

The causes of male erectile dysfunction (ED) are quite variable and are now commonly divided into etiologies such as ischemia, smooth muscle damage, or altered blood flow. Although varying rates of ED have been reported in literature, the number of men with ED is projected to increase worldwide by 2025 to approximately 322 million. Since the introduction of phosphodiesterase 5 (PDE5) inhibitors, there has been a paradigm shift in the treatment of ED because PDE5 inhibitors address a broad spectrum of etiologies for ED. Today, the American Urological Association recommends the use of three PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) as a first-line therapy for the treatment of ED. This review evaluates the pharmacological mechanism of PDE5 inhibitors along with the impact and use of sildenafil, vardenafil, tadalafil, and avanafil. By increasing intracellular cGMP levels, PDE5 inhibitors have been shown to be effective in the treatment of ED. Through their effects on other cellular signaling pathways, PDE5 inhibitors have the potential for treating other urologic conditions as well. The use of PDE5 inhibitors can also be combined to produce a synergistic effect in conditions such as male hypogonadism and benign prostatic hyperplasia in addition to ED.

Tadalafil once daily: Narrative review of a treatment option for female sexual dysfunctions (FSD) in midlife and older women

“…Pharmacotherapy for treating FSD is still under investigation and, to date, no treatments have been approved by the Food and Drug Administration (32). PDE5i have been used in the treatment of erectile dysfunction with acceptable results (33). The treatment with PDE5i can decrease the catabolism of cyclic GMP also in female individuals, resulting in the relaxation of clitoral and vaginal smooth muscle, increasing local blood flow (32).…”

Influence of drugs on smelling capacity. A review

“…Therefore, PDE 5 inhibitors induce higher cyclic GMP levels. The indication of sildenafil is the treatment of erectile dysfunction . The effects of sildenafil on olfactory capability were explored in a placebo‐controlled, double‐blinded crossover study.…”

Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

“…This disease is defined by the National Institute of Health as the incapacity to achieve and sustain a satisfactory erection for the purposes of sexual intercourse [18]. The inhibition of PDE 5 results in a blockade of cGMP hydrolysis that leads to an increase of cGMP level, and, subsequently, to a growth in NO concentration.…”

“…NO is responsible for vasodilation in the corpus cavernosum -a dilation of the smooth muscle and blood vessels in the penis that brings about a stiff erection. This group of drugs is characterized by having a tolerable sideeffect profile, by effectiveness and quick onset of action [13,18]. Of interest, their administration could enhance NOmediated vasodilation in other vascular beds and improve endothelial function [18].…”

“…Besides erectile dysfunction therapy, it can selectively utilized in reducing pulmonary vascular resistance, as well as in improving pulmonary artery pressure and physical exercise tolerance. These effects are of importance in the treatment of persistent pulmonary hypertension, as characterized by progressive increase in the pulmonary pressure [4,18]. In the therapy of persistent pulmonary hypertension of the newborns, iNO is commonly applied.…”