Efficacy of Sildenafil Citrate (Viagra) in treatment of Erectile Dysfunction: effect of type 2 diabetes.

PURPOSE: To assess efficacy of Sildenafil Citrate (Viagra) in treatment of Erectile Dysfunction: effect of type 2 diabetes. MATERIALS AND METHODS: A total of 466 male patients with Erectile Dysfunction (ED) were enrolled in this study. Of them 382 were diabetic and 84 were non-diabetic. Patients were screened for ED using the erectile function domain of the International Index for Erectile Function (IIEF). Patients underwent routine laboratory investigations, in addition to total testosterone and prolactin assessment. To assess the effect of diabetes on efficacy of sildenafil, we compared the pre and postSildenafil Citrate (Viagra) responses to erectile function domain, Q3, Q4. Overall satisfaction and global efficacy question (GEQ) were also assessed. RESULTS: Mean age +/- S.D. was 53 +/- 8.4 and 49.7 +/- 10.6 years for patients with and without diabetes respectively. There were significant associations between increased severity of ED and longer duration, poor metabolic control and presence of more than one diabetes-related complication (p < 0.05 for each). Differences were significant between pre and postSildenafil Citrate (Viagra) administration regarding erectile function domain, Q3, Q4 (p < 0.05 for each). In the non-diabetic patients the GEQ and the overall satisfaction were significantly higher than in diabetics (p < 0.05 for each). Global efficacy question was significantly low in patients with fair and poor metabolic control, longer duration of diabetes, and patients with diabetic complications (p < 0.05 for each). CONCLUSIONS:Sildenafil Citrate (Viagra) is an effective treatment for diabetic patients with ED. Although the efficacy ofSildenafil Citrate (Viagra) was negatively affected by factors as poor control and longer duration of diabetes and presence of more than one diabetes-related complication, however, the global efficacy and the overall patients' satisfaction were high

Reasons for discontinuation of Sildenafil Citrate (Viagra) after successful restoration of erectile function.

AIM: To investigate the reasons for discontinuations ofSildenafil Citrate (Viagra) after the successful restoration of erectile function. METHODS: One hundred fifty six patients, whose scores of erectile function domain of the 15-item International Index of Erectile Function (IIEF) increased to 26 or more afterSildenafil Citrate (Viagra) medication, were included in this study. Six-months after the firstSildenafil Citrate (Viagra) prescription, compliance to medication and the reason for discontinuity were reviewed by chart or surveyed by telephone. RESULTS: Fifty-four (34.6 %) of the 156 successfully treated patients discontinuedSildenafil Citrate (Viagra) medication. The reasons for discontinuance were shortcomings in the partners' or patients' emotional readiness for the restoration of sexual life after long-term abstinence (37.0 %), fear of possible side effects (18.5 %), recovery of spontaneous erection (14.8 %), postponement of ED treatment because of co-morbid disease treatment (11.1 %), unwillingness to accept drug-dependent erection (7.4 %), high drug cost (3.7 %), unacceptability of planned sexual activity (3.7 %) and lack of sexual interest (3.7 %). CONCLUSION: The reasons for discontinuingSildenafil Citrate (Viagra) medication were primarily emotional or relationship-oriented, which indicates that simple recovery of a rigid erection is insufficient to restore sexual activity. More education about the effects of drug and the counseling of both partners is recommended to promote the successful recovery of sexual activity

Cyclic nucleotide phosphodiesterase type 5 activity limits blood flow to hypoperfused myocardium during exercise.

BACKGROUND: Nitric oxide (NO) causes vasodilation by stimulation of guanylate cyclase in vascular smooth muscle to produce cGMP. The resultant vasodilator effect is regulated by a family of cGMP phosphodiesterases (PDEs). Sildenafil, a selective inhibitor of PDE5 used for treatment of Erectile Dysfunction, has been found to cause relaxation of isolated epicardial coronary artery segments. The present study examined the effects ofSildenafil Citrate (Viagra) on coronary blood flow and hemodynamics during exercise in normal and ischemic heart. METHODS AND RESULTS: In chronically instrumented normal dogs,Sildenafil Citrate (Viagra) 2 mg/kg PO caused a slight but significant increase in left anterior descending (LAD) coronary blood flow during resting conditions, with a nonsignificant trend toward increased coronary flow during treadmill exercise. Exercise in the presence of LAD stenosis that decreased distal coronary pressure to 57+/-2 mm Hg reduced LAD flow during exercise from 69+/-8 to 41+/-7 mL/min (P:<0. 05), with hypoperfusion most severe in the subendocardium. At the same distal coronary pressure,Sildenafil Citrate (Viagra) increased LAD flow in the ischemic region to 50+/-11 mL/min (P:<0.05). Increase in ischemic region blood flow produced bySildenafil Citrate (Viagra) was uniform across the LV wall, given that no change occurred in the transmural distribution of perfusion. CONCLUSIONS: Inhibition of PDE5 withSildenafil Citrate (Viagra) caused vasodilation of coronary resistance vessels with an increase of blood flow into an ischemic myocardial region during exercise in the presence of coronary artery stenosis

Development of a liquid chromatographic method for bioanalytical applications with sildenafil.

An improved HPLC method was developed for the determination ofSildenafil Citrate (Viagra) concentrations in plasma. Analysis ofSildenafil Citrate (Viagra) in plasma samples was simplified by utilizing a one-step liquid-liquid extraction after alkaline treatment of only 1 ml of plasma. The lower limit of quantitation was 10 ng/ml with a coefficient of variation of less than 20%. A linear range was found to exist from 10 to 1000 ng/ml. This HPLC method was validated with precisions (coefficient of variation, C.V.) for inter- and intra-day runs of 0.41-11.15% and 0.36-8.05%, respectively, and accuracies (the relative error of the mean, REM) for inter- and intra-day runs of -8.72-6.81% and 0.41-11.15%, respectively. A bioavailability study ofSildenafil Citrate (Viagra) was performed on one normal healthy male volunteer by analyzingSildenafil Citrate (Viagra) plasma concentrations with this validated HPLC method. Results demonstrated that this HPLC method is appropriate for applications to bioavailability studies of sildenafil. In addition, an example of the influence of the co-administration of grapefruit juice onSildenafil Citrate (Viagra) pharmacokinetics in a healthy volunteer is presented

HPLC-MS for the determination of Sildenafil Citrate (Viagra) in biological fluids. Application to the salivary excretion ofSildenafil Citrate (Viagra) after oral intake.

An original high-performance liquid chromatography-mass spectrometry (HPLC-MS) procedure was developed for the determination ofSildenafil Citrate (Viagra) in biological fluids. Liquid-liquid extraction was performed by chloroform/2-propanol/n-heptane (25:10:65, v/v) at pH 9.5 with 300 ng of buprenorphine-d4 as the internal standard (IS). After agitation (10 min) and centrifugation (3500 x g, 10 min), the organic phase was evaporated and the dry extract resuspended in 25 microL methanol, from which 2 microL was injected onto a NovaPak C18 (Waters) HPLC column. Separation was carried out by a gradient of (acetonitrile + 10 microg/mL trimethylamine) in 2mM NH4COOH pH 3.0 buffer (35-70% in 9 min). Detection was done by a PerkinElmer Sciex API-100 single-quadrupole mass analyzer with an ionspray interface operated in positive-ion mode. MS data were collected as either TIC or SIM at m/z (475 + 534) or (475 + 283) for sildenafil, depending on the potential applied at the ion sampling orifice (0 V or + 100 V). The retention times ofSildenafil Citrate (Viagra) and the IS were 4.20 and 5.07 min, respectively. Extraction recoveries were always > 87%. LOD and LOQ were 0.2 and 0.5 ng/mL whatever the biological fluid tested. The method appears specific, extremely sensitive, and relatively simple in both equipment and sample preparation. As an example, we present the results of a preliminary study on the salivary excretion ofSildenafil Citrate (Viagra) following the oral intake (T0) of 25 mg Viagra in a 38-year-old volunteer.Sildenafil Citrate (Viagra) was detectable in oral fluid at T0 + 0.5 h (1.2 ng/mL) and peaked at T0 + 1.5 h (8.3 ng/mL), whereas at the same time its plasma concentration was 72.4 ng/mL. Salivary concentrations then rapidly decreased, and the last detectable value (0.9 ng/mL) was at T0 + 5.5 h. It is suggested that the salivary excretion pattern ofSildenafil Citrate (Viagra) resembles that of benzodiazepines (high plasma protein binding, low saliva-to-plasma ratio)

Effect of combination endothelial nitric oxide synthase gene therapy andSildenafil Citrate (Viagra) on erectile function in diabetic rats.

Erectile Dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination ofSildenafil Citrate (Viagra) and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats +Sildenafil Citrate (Viagra) (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administeredSildenafil Citrate (Viagra) demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal. STZ-diabetic rats transfected with AdCMVeNOS and administeredSildenafil Citrate (Viagra) had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination withSildenafil Citrate (Viagra) significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plusSildenafil Citrate (Viagra) than STZ-rats receivingSildenafil Citrate (Viagra) or eNOS gene therapy alone

Overactive corpus cavernosum: a novel cause of Erectile Dysfunction.

Our recording of the electromyographic (EMG) activity of the corpus cavernosum (CC) in 59 patients with Erectile Dysfunction (ED) revealed 18 patients who had elevated electric activity, which presumably points to heightened tone of the CC smooth muscles. We investigated the hypothesis that this elevated EMG activity and muscular tone of the CC could be the cause of ED. The study comprised the said 18 subjects with the hypertonic CC muscles as study group (42.6 +/- 5.3 SD years), 15 healthy volunteers (41.8 +/- 5.1 SD years) and 15 patients (41.6 +/- 5.5 SD years) with ED who had not recorded elevated tone of the CC muscles as control group. The EMG activity was registered in the flaccid, erectile and detumescent phases by two electrodes inserted into the CC. Electrocavernosography (ECG) of healthy volunteers recorded in the flaccid phase showed regular slow waves (SW) and random action potentials (APs). The wave variables declined significantly in the erection phase (P < 0.01). In the study group, the SW variables in the flaccid phase increased significantly (P < 0.05) compared with the healthy volunteers and the rhythm was irregular. erection did not occur withSildenafil Citrate (Viagra) but with intracavernosal injection of papaverine, which led to decline of the SW variables (P < 0.05). The control ED group exhibited in the flaccid phase diminished SW variables (P < 0.05) compared with the healthy volunteers. On erection withSildenafil Citrate (Viagra) administration, the SW variables showed significant reduction (P < 0.05). CC hypertonicity or 'overactive CC' was identified as a possible cause of ED. An elevated EMG activity of the CC muscle fibres in the flaccid phase presumably denotes hypertonicity of these fibres and their failure to relax to effect erection. The cause of elevated CCEMG activity and presumed muscle hypertonicity is unknown and could be functional or organic. erection was produced by intracavernosus injection of papaverine and not by sildenafil. This condition of 'overactive CC' should be considered in the diagnosis of ED. However, further studies in the pathogenesis of the condition are warranted

Sildenafil Citrate (Viagra) for the management of antidepressant-associated Erectile Dysfunction.

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated Erectile Dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, Erectile Dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil Citrate (Viagra), a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability ofSildenafil Citrate (Viagra) in the treatment of antidepressant-associated Erectile Dysfunction have been confirmed in double-blind, placebo-controlled trials