The effects of the combined use of a PDE5 inhibitor and medications for hypertension, lower urinary tract symptoms and dyslipidemia on corporal tissue tone

Abstract

ED is closely associated with its comorbidities (hypertension, dyslipidemia and lower urinary tract symptoms (LUTS)). Therefore, several drugs have been prescribed simultaneously with PDE5 inhibitors. If a specific medication for ED comorbidities has enhancing effects on PDE5 inhibitors, it offers alternative combination therapy in nonresponders to monotherapy with PDE5 inhibitors and allows clinicians to treat ED and its comorbidities simultaneously. To establish theoretical basis of choosing an appropriate medication for ED and concomitant disease, we examined the effects combining a PDE5 inhibitor with representative drugs for hypertension, dyslipidemia and LUTS on relaxing the corpus cavernosum of rabbits using the organbath technique. The effect of mirodenafil on relaxing phenylephrine-induced cavernosal contractions was significantly enhanced by the presence of 10 À4 M losartan, 10 À6 M nifedipine, 10 À6 M amlodipine, 10 À7 M doxazosin and 10 À9 M tamsulosin (Po0.05). The maximum relaxation effects were 47.2 ± 3.8%, 57.6 ± 2.6%, 64.0 ± 3.7%, 76.1 ± 5.7% and 71.7 ± 5.4%, respectively. Enalapril and simvastatin had no enhancing effects. The relaxation induced by sodium nitroprusside alone (39.0±4.0%) was significantly enhanced in the presence of the 10 À4 M losartan (66.0 ± 6.0%, Po0.05). Tetraethylammonium (1 mM) significantly inhibited the enhancement effects of tamsulosin and doxazosin on mirodenafil-induced relaxation (doxazosin: 76.1 ± 5.7% vs 45.3 ± 2.3%; tamsulosin: 71.7±5.4% vs 48.1±3.5%). On the basis of these findings, losartan seemed to induce synergistic effects through an interaction with nitric oxide. In addition, K þ channel activation could be one of the mechanisms for the synergistic effect of combining mirodenafil with doxazosin or tamsulosin. We believe that the combination of a PDE5 inhibitor with losartan, nifedipine, amlodipine, doxazosin or tamsulosin could be a pharmacologic strategy for simultaneously treating ED and its comorbidities and increasing response rates to PDE5 inhibitors.International Journal of Impotence Research (2012) 24, 221--227; doi:10.1038/ijir.2012; published online 5 July 2012Keywords: comorbidity; ED; PDE5 inhibitor INTRODUCTION ED is a common condition, with a reported prevalence of 52% in men aged 40--70 years in the United States 1 and 49% in men aged 50--80 years in Europe.2 It can affect patients' lives in different ways, including disrupting interpersonal relationships, interfering with sexual life, causing problems with partners and increasing stress, all of which make ED a major quality of life issue.

Mirodenafil for the Treatment of Erectile Dysfunction: A Systematic Review of the Literature

“…However, a more important clinical issue is the relationship between ED and hypertension, and the possible interaction between mirodenafil and antihypertensive drugs. In an experimental study of the effects combining mirodenafil with antihypertensive drugs on the relaxation of rabbits' corpus cavernosum [35], the effect of mirodenafil was significantly enhanced by an angiotensin receptor blocker (losartan), a calcium channel blocker (nifedipine or amlodipine), and an alpha adrenergic blocker (doxazosin or tamsulosin) by >40%, but not by an angiotensin-converting enzyme inhibitor. These results are comparable to those of other PDE5 inhibitors and suggest that mirodenafil, like other PDE5 inhibitors, should be initiated at a lower dose in patients using hypertensive drugs.…”

A review of the efficacy and safety of mirodenafil in the management of erectile dysfunction

“…Thus, the pharmacokinetics of mirodenafil does not appear to be affected by essential hypertension itself. According to a recent organ-bath study using corporal tissue strips to evaluate the interaction of mirodenafil with antihypertensive drugs, angiotensin receptor blocker (losartan), calcium channel blocker (nifedipine and amlodipine), α-adrenergic blocker (tamsulosin and doxazosin) except for angiotensin-converting enzyme (ACE) inhibitor (enalapril), enhanced mirodenafil-induced relaxation on phenylnephrine-contracted corpus cavernosum of rabbits, indicating that the combination of PDE5Is with the above-mentioned drugs could be a pharmacologic strategy for simultaneously treating ED and its comorbidities and for increasing response rates to PDE5Is [Lee et al 2012].…”

Effect of an angiotensin II receptor blocker and a calcium channel blocker on hypertension associated penile dysfunction in a rat model

“…Nifedipine and amlodipine, L-type calcium channel blockers, are widely used as the important drugs in the treatment of hypertension and coronary heart diseases (21). Calcium channel blockers are known to induce relaxation effect on the corpus cavernosum in vitro study (20). Toblli et al investigated the effects of an ARB losartan and a calcium channel blocker amlodipine on the SHR penis (33).…”