Efficacy of vardenafil andSildenafil Citrate (Viagra) in facilitating penile erection in an animal model.

Vardenafil andSildenafil Citrate (Viagra) are potent and specific phosphodiesterase type 5 (PDE 5) inhibitors. In human penile cavernosal smooth muscle cells, we have previously shown that vardenafil has a lower biochemical inhibition constant (Ki) than sildenafil. In this study, we compared the efficacy of vardenafil andSildenafil Citrate (Viagra) in facilitating penile erection in a rabbit model. Penile erections were elicited by submaximal (2.5 or 6 Hz) pelvic nerve stimulation (PNS) repeated every 5 minutes for 30 minutes with or without intravenous (i.v.) administration of vardenafil (1-30 microg/kg) orSildenafil Citrate (Viagra) (10-30 microg/kg). Erectile response was assessed by continuously recording intracavernosal pressure (ICP) and systemic arterial pressure (SAP). All data were expressed as a ratio of ICP:SAP. I.v. administration of either PDE 5 inhibitor facilitated PNS-induced erection and increased ICP:SAP in a dose-dependent manner, reaching peak response at approximately 5 minutes. However, the threshold dose at which facilitation of erection occurred was lower for vardenafil (3 microg/kg) than forSildenafil Citrate (Viagra) (10 microg/kg). At the 10-microg/kg dose (i.v.), the response duration was significantly greater with vardenafil (169 +/- 23 seconds) than withSildenafil Citrate (Viagra) (137 +/- 31 seconds). Direct intracavernosal (i.c.) injection of 1-30 microg/kg vardenafil orSildenafil Citrate (Viagra) also caused dose-dependent increases in ICP:SAP in the absence of PNS. Response durations increased in a dose-dependent manner and lasted more than 5 times that of i.v. drug administration coupled with PNS. Irrespective of the route of administration (i.c. or i.v.), at equivalent doses, vardenafil was significantly more efficacious thanSildenafil Citrate (Viagra) in facilitating pelvic nerve-mediated penile erection and in eliciting erection in the absence of PNS. The increases in ICPs occurred more quickly, were of larger magnitude, and were sustained for longer durations for vardenafil than for sildenafil. On the basis of the biochemical data and physiological responses from this study, further clinical evaluation of vardenafil as treatment for Erectile Dysfunction is warranted

Inhibition of angiotensin converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure.

Angiotensin converting enzyme (ACE) inhibitors and phosphodiesterase type 5 (PDE5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been previously studied. We sought to characterize the acute effects of ramipril alone,Sildenafil Citrate (Viagra) alone, or their combination on endothelial function in patients with chronic heart failure (CHF). 64 CHF subjects were randomized to receive placebo, ramipril 10 mg alone,Sildenafil Citrate (Viagra) 50 mg alone, or the combination of ramipril andSildenafil Citrate (Viagra) in a double-blind manner. Flow-mediated dilation (FMD) of the brachial artery was determined by high-resolution ultrasound imaging before and at 1, 2, and 4 hours after study drug. Ramipril alone increased FMD at 4 hours when compared with placebo (+2.3+/-1.3%, p=0.02).Sildenafil Citrate (Viagra) alone increased FMD at 1, 2 and 4 hours when compared with placebo (+3.9+/-1.4, +4.6+/-1.8, and +3.7+/-1.3% respectively, all p<0.02).Sildenafil Citrate (Viagra) in combination with ramipril increased FMD at 1, 2, and 4 hours when compared with placebo (+3.5+/-1.5, +4.5+/-1.8, and +4.8+/-1.3% respectively, all p< 0.03). Ramipril andSildenafil Citrate (Viagra) both acutely improved FMD in patients with CHF, with additive effects evident at 4 hours during combination therapy. Further work to characterize chronic effects of combined ACE and PDE5 inhibition on endothelial function are warranted

Erectile Dysfunction after kidney transplantation: our 22 years of experience.

AIM: To evaluate the results of treatment of Erectile Dysfunction (ED) in kidney transplant recipients before and after the advent of sildenafil. MATERIALS AND METHODS: From 1981 through 2002, 971 male patients of mean age 53.4 years received a renal graft. Erectile Dysfunction (ED) was investigated in all patients at the first urologic visit posttransplantation. Psycho-sexual support was offered to all patients. BeforeSildenafil Citrate (Viagra) use (1998), our diagnostic approach was complex. From 1998 we tested: serum levels of testosterone, prolactin, and glucose with penile duplex ultrasonography and NPT reserved for selected cases. RESULTS: From 1981 through 1998, 365 male kidney transplant recipients (45%) reported ED. Only 169 patients chose to be treated: 27 responded to psycho-sexual therapy; 3 received testosterone with benefit; 133 had a good results from intracavernosal injection of vasoactive drugs; and 6 received a penile prosthesis. Since 1998, 126 patients reported ED (78.3%). Only 78 chose treatment: 24 patients had a satisfactory response toSildenafil Citrate (Viagra) (65% with 50 mg and 35% with 100 mg). PGE1 alone or in combination with papaverine and phentolamine produced a good response in 37 patients; 17 patients did not respond to pharmacotherapy; and 5 received a tricomponent penile prosthesis without complications. The side effects ofSildenafil Citrate (Viagra) and PGE1 therapy were similar to those reported in the literature. CONCLUSIONS: ED is an important problem in male renal transplant recipients. Cultural resistance to treatment is common. However, treatment with Sildenafil Citrate (Viagra) and intracavernosal self-injection of PGE1 are well accepted, and prosthetic devices may help in resistant cases

Effect ofSildenafil Citrate (Viagra) on ocular haemodynamics.

PURPOSE: To study the effect of sildenafil, which is an effective agent for the treatment of Erectile Dysfunction, on ocular haemodynamics. METHODS: In this prospective study we examined the effect of a single oral dose of 50 mg Sildenafil Citrate (Viagra) in a group of healthy young male volunteers, by using colour Doppler ultrasound imaging to measure haemodynamic variables in the central retinal artery (CRA), short temporal posterior ciliary artery (STPCA) and ophthalmic artery (OA). The following examinations were performed on both eyes immediately before and 1 h after a single oral dose of 50 mg sildenafil: visual acuity, intraocular pressure (IOP), colour vision, anterior segment, fundus appearance, resting heart rate, blood pressure and colour Doppler measurements. RESULTS: AfterSildenafil Citrate (Viagra) administration, peak systolic velocity, mean velocity and end-diastolic velocity significantly increased in the OA of both eyes. All Dopper indices remained non-significant for the CRA and STPCA of both eyes.Sildenafil Citrate (Viagra) did not cause any significant change in IOP, colour vision, visual acuity, systolic blood pressure or diastolic blood pressure. However, heart rate measurements increased significantly afterSildenafil Citrate (Viagra) administration compared with baseline (p = 0.003). CONCLUSION: The increased flow velocity in the ophthalmic artery seems to be due to a vasodilator effect ofSildenafil Citrate (Viagra)

Sildenafil Citrate (Viagra).

Sildenafil is the first of a series of orally active treatments for MED which has resulted in unprecedented demand for treatment and potentially high cost to the NHS. Further oral therapies are likely to follow in the next year or so. In clinical trials,Sildenafil Citrate (Viagra) produced an erection (sufficient to achieve intercourse) lasting up to 4 h on around 70% of occasions. This was reduced to 50% in 'high-risk' groups (e.g. diabetics) and a placebo response in as many as 10-20% has been reported. Whether or notSildenafil Citrate (Viagra) should be prescribed at NHS expense has been more a matter for political, than clinical, debate. A clearer picture is now emerging with treatment available to those considered the 'most deserving' cases. The bigger picture is of impotence in large numbers of men with hypertension who are on antihypertensive therapy and have obvious small vessel disease. One option is to consignSildenafil Citrate (Viagra) to Schedule 10 (Black List) so that it is only available on private prescription. This would allay fears of the cost of treatment for those merely seeking to 'boost' already adequate sexual performance

Fatal variceal rupture afterSildenafil Citrate (Viagra) use: Report of a case.

Sildenafil may increase the risk of variceal bleeding in portal hyptertension by increasing splanchnic blood flow. We report herein the second case of variceal rupture afterSildenafil Citrate (Viagra) use

Clinical study ofSildenafil Citrate (Viagra) in the treatment of premature ejaculation complicated by Erectile Dysfunction

OBJECTIVES: To evaluate the efficacy and safety of sidenafil citrate in the treatment of premature ejaculation (PE) complicated by Erectile Dysfunction (ED). METHODS: Forty-five patients of PE complicated by ED received flexible doses ofSildenafil Citrate (Viagra) from 50 to 100 mg for 1 to 3 months. Intravaginal ejaculatory latency time (IELT) and sexual satisfaction ratio (SSR) of partner were recorded to evaluate the effect of PE treatment, as well as the general efficacy and satisfaction of ED treatment. And the difference of IIEF-5 before and after the treatment were compared. RESULTS: Twenty-seven patients had their PE improved and the effective rate was 60%. Forty patients reported the improvement in erection and the percentage of erectile improvement was 88.88%. All the 27 patients with improvement of PE achieved effective erection through the administration of 50 mgSildenafil Citrate (Viagra) and the satisfaction rate reached 81.48%. On the other hand, only 1 case (5.56%) reported satisfaction over the treatment in the 18 patients who did not obtain improvement of PE. Between the PE improvement group and non-improvement group, there were significant differences (P < 0.001) shown in IIEF-5 scores before and after the treatment. Mild or moderate side effects were reported in 9 patients(20%), who recovered without any treatment. CONCLUSIONS: To premature ejaculation patients with ED,Sildenafil Citrate (Viagra) can safely and effectively improve their erectile function, the satisfaction over the ED treatment outcome means that their PE symptoms could be alleviated

Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) bySildenafil Citrate (Viagra) and related compounds.

The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis. Sildenafil Citrate (Viagra), a specific PDE5 inhibitor, promotes penile erection by blocking the activity of PDE5, which causes cGMP to accumulate in the corpus cavernosum. In the present study, sildenafil, like other PDE5 inhibitors, stimulates cGMP binding to the allosteric sites of PDE5 by interacting at the catalytic site of this enzyme, but the drug does not compete with cGMP for binding at the allosteric sites. BothSildenafil Citrate (Viagra) and zaprinast are competitive inhibitors of PDE5, and double-inhibition analysis shows that these two inhibitors added together interact with the catalytic site of PDE5 in a mutually exclusive manner. After site-directed mutagenesis of each of 23 conserved amino acid residues in the catalytic domain of PDE5, the pattern of changes in the IC50 values forSildenafil Citrate (Viagra) or UK-122764 is similar to that found for zaprinast. However, among the three inhibitors,Sildenafil Citrate (Viagra) exhibits the most similar pattern of changes in the IC50 to that found for the affinity of cGMP, implying similar interactions with the catalytic domain. This may explain in part the stronger inhibitory potency ofSildenafil Citrate (Viagra) for wild-type PDE5 compared with the other inhibitors [sildenafil (Ki = 1 nM) > UK-122764 (Ki = 5 nM) > zaprinast (Ki = 130 nM)]. The affinity of each of these inhibitors for PDE5 is much higher than that of cGMP itself (Km = 2000 nM). It is concluded that residues such as Tyr602, His607, His643, and Asp754 may form important interactions forSildenafil Citrate (Viagra) in PDE5, but because these amino acids are conserved in all mammalian PDEs, the selectivity and potency ofSildenafil Citrate (Viagra) is likely to be provided by a nonconserved residue or residues in the PDE5 catalytic domain