sildenafil-citrate and alfuzosin

To critically review the physiological roles of phosphodiesterase-5 (PDE5), to explain and support the putative impact and clinical significance of PDE5 inhibitors (PDE5-Is) in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both highly prevalent in men aged > or =50 years, as PDE5-Is are very effective as a first-line therapy for ED, and attractive for further physiological functional investigations.. We searched Medline for peer-reviewed articles in English, from 1991 to 2008, to provide a critical contemporary review of PDE5 pertaining to the potential interest of findings supporting a role for PDE5-Is in LUTS due to BPH. The selection of papers was based on the relevance of subject matter. A critical analysis of available fundamental and clinical data is reported.. Several studies assessed the role of the nitric oxide/cGMP signalling pathway in the regulation of the prostate tone, with the support of clinical observations. PDE5-Is can also represent a potential mode of action allowing the targeting of transcriptional activity implicated in the regulation of the progression of the inflammatory process involved in BPH. PDE5-Is can inhibit human stromal cell proliferation of the prostate mediated by cGMP accumulation. New targeting hypotheses of pathophysiological processes are also reported.. There is evidence that LUTS and ED are strongly linked. This analysis of the regulatory basis of PDE5 biology could indicate several directions of investigation. However, it is necessary to devise well-designed large prospective studies that would produce significant data before this approach becomes a standard of care.

Topics: Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Prostatism; Purines; Quality of Life; Quinazolines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are frequently encountered in ageing males. We compared the efficacy of alfuzosin 10 mg alone or in combination with sildenafil 50 mg in the treatment of LUTS due to benign prostatic hyperplasia. One hundred male patients older than 45 years were randomized to two groups containing 50 patients each; one group receiving alfuzosin 10 mg and the other group alfuzosin 10 mg combined with sildenafil 50 mg. International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Q(max)), prostate volume and post-void residual urine were evaluated. The mean age was 60.2 ± 17.8. Mean data of evaluated parameters in both groups at the end of 3rd month compared with baseline values are given respective order as; 5.1 (26.8%) and 5.8 (28.2%) points decreases in IPSS; 1.6 (41.1%) and 1.8 (45%) points decreases in QoL; and 3.4 (29.6%) and 3.4 (33%) points increases in Q(max) . The outcomes of our study cannot be interpreted in such a way to report that alpha blocker-PDE5 inhibitor combination has a better efficacy than alpha blocker treatment alone in patients with LUTS.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Aged; Drug Therapy, Combination; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Purines; Quinazolines; Sildenafil Citrate; Sulfones; Urination Disorders

This pilot study was undertaken to assess the efficacy and safety of the alpha(1)-blocker alfuzosin 10mg once daily (OD), the PDE-5 inhibitor sildenafil 25mg OD, and the combination of both on lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED).. Men aged 50-76 yr with previously untreated LUTS and ED were randomized to receive alfuzosin (n=20), sildenafil (n=21), or the combination of both (n=21) for 12 wk. Changes from baseline in International Prostate Symptom Score (IPSS), voiding diary, maximum urinary flow rate (Qmax), postvoid residual urine (PVRU) volume, and erectile function domain of the International Index of Erectile Function (IIEF) were assessed at week 12.. Improvement of IPSS was significant with the three treatments but greatest with the combination (-24.1%) compared with alfuzosin (-15.6%) and sildenafil (-11.8%) [corrected] alone (p<0.03). Frequency, nocturia, PVR, and Qmax were significantly improved with alfuzosin only and the combination. Improvement in IIEF was slight with alfuzosin (16.7%), marked with sildenafil (49.7%), and greatest with the combination (58.6%). Likewise, increases in the frequency of penetration (Q3) and of maintained erection (Q4) were greater with the combination therapy (65.2% and 68.2%, respectively) than with sildenafil (41.7% and 59.1%, respectively) and alfuzosin (27.3% and 33.3%, respectively) alone. All three treatments were well tolerated.. In this pilot study, the combination of alfuzosin 10 mg OD and sildenafil 25 mg OD is safe and more effective than monotherapy with either agent to improve both voiding and sexual dysfunction in men with LUTS suggestive of BPH.

Topics: Adrenergic alpha-Antagonists; Aged; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Pilot Projects; Piperazines; Prostatic Hyperplasia; Purines; Quinazolines; Sildenafil Citrate; Sulfones; Treatment Outcome; Urination Disorders

Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Micelles; Quinazolines; Sildenafil Citrate

Topics: Adrenergic alpha-Antagonists; Age Factors; Aged; Drug Therapy, Combination; Enzyme Inhibitors; Erectile Dysfunction; Humans; Male; Middle Aged; Piperazines; Prevalence; Prostatic Hyperplasia; Purines; Quality of Life; Quinazolines; Risk Factors; Sildenafil Citrate; Sulfones; Urination Disorders

To compare the direct relaxant effects of alfuzosin, phentolamine and sildenafil in rabbit isolated corpus cavernosum (CC) pre-contracted with phenylephrine or KCl.. Penile erectile tissue was obtained from male New Zealand White rabbits (22-26 weeks old). The CC was cut into longitudinal strips and mounted under 2 g resting tension in 5-mL jacketed organ baths containing a modified Krebs solution bubbled with 95% O2, 5% CO2 and maintained at 37 degrees C. Tissue strips were pre-contracted by 60 mmol/L KCl or 10 micro mol/L phenylephrine. After obtaining a stable plateau of contractions, test compounds were added to the organ bath. The relaxant potencies were expressed as the percentage of inhibition of the plateau of contraction induced by 10 micro mol/L phenylephrine.. Alfuzosin showed a concentration-dependent relaxing effect on rabbit CC pre-contracted by 10 micro mol/L phenylephrine, with a mean (sd) pIC50 of 7.64 (0.06). The relaxant effect was unaffected by pre-incubation with 100 micro mol/L Nomega-nitro-l-arginine methyl ester (L-NAME). Phentolamine had a potency similar to alfuzosin, with a pIC50 of 7.44 (0.08). Both alfuzosin and phentolamine were completely ineffective on the plateau of contraction induced by 60 mmol/L KCl. In contrast to alfuzosin, sildenafil was equipotent in relaxing the rabbit CC against each contractile agent, with pIC50 values of 7.25 (0.09) and 7.23 (0.22) with 10 micro mol/L phenylephrine and 60 mmol/L KCl, respectively. The relaxant response to sildenafil was partly blocked by pretreatment with 100 micro mol/L L-NAME, with pIC50 values of 7.94 (0.09) and 6.63 (0.32) without and with L-NAME, respectively. Sildenafil, incubated for 45 min at 10 micro mol/L, had no relaxant effect on the resting tension of the preparation or on the concentration-response curve to phenylephrine.. The direct relaxant effect of alfuzosin is mediated through alpha1-adrenoceptor blockade. The relaxations induced by phentolamine and alfuzosin are independent of nitric oxide, whereas those induced by sildenafil are, at least partly, sensitive to L-NAME and a selective soluble guanylate cyclase inhibitor, indicating the involvement of nitric oxide and soluble guanylate cyclase. Alfuzosin and phentolamine effectively counteract alpha1-adrenoceptor-mediated contractions of rabbit CC. If valid for human CC, such an effect may contribute to an improved erectile function in patients treated for benign prostatic hyperplasia.

Topics: Adrenergic alpha-Antagonists; Animals; Erectile Dysfunction; Male; Muscle Relaxation; Penile Erection; Phentolamine; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Purines; Quinazolines; Rabbits; Sildenafil Citrate; Sulfones