[Continuous use of PDE5 inhibitors in the treatment of erectile dysfunction: New insights and opportunities]. / Uso continuado de inhibidores de la PDE5 en el tratamiento de la disfunción eréctil: nuevas perspectivas y oportunidades.

At present, there is debate regarding the continuous use of phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Cumulative evidence supports the benefit, even at low doses, thatcontinuous treatment has on erectile function -even in difficult-to-treat patients-, and on the spontaneity and naturalness of sexual relationships. Safety and tolerability have also proven to be good. Beyond phosphodiesterase 5 inhibition, the effect of continuous treatment of erectile function appears to be based on improvement of endothelial function and oxygenation of the penile vascular bed as a result of the increased number of erections, hence playing down the importance of pharmacokinetics. Although evidence is still limited, this new scenario opens new paths for the treatment of erectile dysfunction patients in whom on-demand treatments are not effective or deemed appropriate, and would benefit the spontaneity of sexual life.

Relationship Between Erectile Dysfunction, Diabetes and Dyslipidemia in Hypertensive-Treated Men.

PURPOSE: PRESIDEN study is a large study to analyze the erectile dysfunction (ED) incidence in Spanish population. The present study is a pilot sub-analysis from PRESIDEN to determine if ED or plasma testosterone (TST) level in controlled hypertensive patients may be associated with comorbidities and/or plasma nitrite+nitrate and antioxidant capacity. MATERIALS AND METHODS: Forty-four hypertensive individuals were aleatory selected from PRESIDEN study, matching by age (28 showing ED and 16 without ED). RESULT: Diabetes was present in 28.57% of ED patients and in 18.75% of patients without ED. In patients with and without ED, increasing age showed tendency of higher frequency of an additional comorbidity (diabetes or dyslipemia) (P = .09). Apparently, plasma TST levels were lower in older ED patients compared to younger patients with and without ED, although it did not reach statistical significance (P = .69). Older ED patients also showed lower TST levels than older patients without ED, although it was not statistical significant (16.15 ± 2.84 vs 13.91± 2.77; P = .69). Dyslipidemia was showed by 52.17% with lower TST (? nmol/L) while 23.80% of patients with plasma TST levels > 15 nmol/L had dyslipidemia. The percentage of ED patients was similar between patients with low and high TST levels. CONCLUSION: More ED hypertensive patients seem to show two comorbidities (diabetes and dyslipidemia) than hypertensivepatients without ED. Younger patients with ED tended to show more commonly diabetes than older ED patients. Plasma TST levels were not associated with more prevalence of ED but lower plasma TST levels showed tendency to higher prevalence of dyslipidemia.

Uso continuado de inhibidores de la PDE5 en el tratamiento de la disfunción eréctil: nuevas perspectivas y oportunidades / Continuous use of PDE5 inhibitors in the treatment of erectile dysfunction: New insights and opportunities

Actualmente existe un debate acerca del uso continuado de los inhibidores de la fosfodiesterasa 5 en el tratamiento de la disfunción eréctil. Varios estudios apoyan el beneficio que, incluso a bajas dosis, esta estrategia terapéutica tiene sobre la función eréctil -incluso en pacientes considerados difíciles de tratar-, y sobre la espontaneidad y naturalidad de las relaciones sexuales. También ha demostrado además ser bien tolerados y seguros. Más allá de la inhibición de la fosfodiesterasa 5, el efecto sobre la función eréctil parece basarse en la mejora de la función endotelial y de la oxigenación del área vascular peneana resultado del incremento del número de erecciones, restando así importancia a la farmacocinética. Aunque la evidencia es limitada, este nuevo escenario abre nuevas oportunidades en el tratamiento de pacientes para los que el tratamiento a demanda no es efectivo o apropiado, y podría favorecer la espontaneidad de la vida sexual (AU)

At present, there is debate regarding the continuous use of phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Cumulative evidence supports the benefit, even at low doses, thatcontinuous treatment has on erectile function -even in difficult-to-treat patients-, and on the spontaneity and naturalness of sexual relationships. Safety and tolerability have also proven to be good. Beyond phosphodiesterase 5 inhibition, the effect of continuous treatment of erectile function appears to be based on improvement of endothelial function and oxygenation of the penile vascular bed as a result of the increased number of erections, hence playing down the importance of pharmacokinetics. Although evidence is still limited, this new scenario opens new paths for the treatment of erectile dysfunction patients in whom on-demand treatments are not effective or deemed appropriate, and would benefit the spontaneity of sexual life (AU)

Regulation of human penile smooth muscle tone by prostanoid receptors.

We have characterized the prostanoid receptors involved in the regulation of human penile arterial and trabecular smooth muscle tone. Arachidonic acid induced relaxation of human corpus cavernosum strips (HCCS) that was blocked by the cyclo-oxygenase inhibitor, indomethacin, and augmented by the thromboxane receptor (TP) antagonist, SQ29548, suggesting that endogenous production of prostanoids regulates penile smooth muscle tone. TP-receptors mediate contraction of HCCS and penile resistance arteries (HPRA), since the agonist of these receptors, U46619, potently contracted HCCS (EC50 8.3+/-2.8 nM) and HPRA (EC50 6.2+/-2.2 nM), and the contractions produced by prostaglandin F(2alpha) at high concentrations (EC50 6460+/-3220 nM in HCCS and 8900+/-6700 nM in HPRA) were inhibited by the selective TP-receptor antagonist, SQ29548 (0.02 microM). EP-receptors are responsible for prostanoid-induced relaxant effects in HCCS because only prostaglandin E1 (PGE1), prostaglandin E2 and the EP2/EP4-receptor agonist, butaprost, produced consistent relaxation of this tissue (EC50 93.8+/-31.5, 16.3+/-3.8 and 1820+/-1284 nM, respectively). In HPRA, both prostacyclin and PGE1 (EC50 60.1+/-18.4 and 109.0+/-30.9 nM, respectively) as well as the selective IP receptor agonist, cicaprost, and butaprost (EC50 25.2+/-15.2 and 7050+/-6020 nM, respectively) caused relaxation, suggesting co-existence of IP- and EP-receptors (EP2 and/or EP4). In summary, endogenous production of prostanoids may regulate penile smooth muscle contractility by way of specific receptors. TP-receptors mediate contraction in HCCS and HPRA, while the relaxant effects of prostanoids are mediated by EP2- and/or EP4-receptors in HCCS and by EP- and IP-receptors in HPRA.