Sildenafil increases diclofenac antinociception in the formalin test.

The antinociceptive activity of an inhibitor of phosphodiesterase 5, alone or combined with diclofenac, was assessed in the formalin test. Local administration of diclofenac produced a significant antinociception in both phases of the formalin test in female Wistar rats. In contrast, 1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [3,4-d]pyrimidin-5-yl)phenylsulfonyl]-4-methyl piperazine (sildenafil, an inhibitor of phosphodiesterase 5) produced significant antinociception, only during the second phase of the formalin test. Non-effective doses ofSildenafil Citrate (Viagra) (25-100 microg/paw) significantly increased the antinociceptive effect of an inactive dose of diclofenac (25 microg) in both phases of the test. The antinociception produced by the drugs alone or the combination was due to a local action, as its administration in the contralateral paw was ineffective. SinceSildenafil Citrate (Viagra) is a potent and selective inhibitor of phosphodiesterase 5, our results suggest that this drug produced its antinociceptive activity, and increased that of diclofenac, probably through the inhibition of cyclic GMP degradation

Potency after permanent prostate brachytherapy for localized prostate cancer.

PURPOSE: The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy ofSildenafil Citrate (Viagra) were studied. METHODS AND MATERIALS: This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated withSildenafil Citrate (Viagra) were evaluated as to its efficacy. RESULTS: The median follow-up of this cohort was 34 months (6--92), with a median age of 68 years (47--80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p = 0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p = 0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p = 0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response toSildenafil Citrate (Viagra) was significantly better in those patients not treated with NAAD (p = 0.04). CONCLUSIONS: The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who receivedSildenafil Citrate (Viagra) exhibited improved potency in a majority of cases

Synthesis and phosphodiesterase 5 inhibitory activity of newSildenafil Citrate (Viagra) analogues containing a phosphonate group in the 5(')-sulfonamide moiety of phenyl ring.

Synthesis of newSildenafil Citrate (Viagra) analogues containing a phosphonate group in the 5(')-sulfonamide moiety of the phenyl ring, 12a-e, 13a-d, and 14a-d, and evaluation of their in vitro PDE5 inhibitory activity are disclosed. Enzyme assays revealed that maximum 10-fold increase in PDE5 inhibitory activity, compared with sildenafil, was achieved by introducing a phosphonate group in the 5(')-sulfonamide moiety. Docking model of (PDE5: 12d) complex shows that the PDE5-bound conformation of 12d matches completely with that of sildenafil, while 12d is partially overlapped with cGMP with ethyl phosphonate group of 12d superimposed onto the cyclic phosphate group of cGMP

Initial uptake in use ofSildenafil Citrate (Viagra) in general practice.

OBJECTIVE: To assess the initial uptake in use and co-prescribing patterns of sildenafil. METHODS: We examined prescription details of the Eastern Health Board Region (including Dublin) of the General Medical Services (GMS) in Ireland, which provides detail on prescriptions dispensed in primary care for this population (n = 334,031). We identified 1422 patients who received 3740 prescriptions forSildenafil Citrate (Viagra) over a 6-month period (July 1999-December 1999) and determined the percentage of patients who were co-prescribed nitrate therapy, medications which may interact withSildenafil Citrate (Viagra) and medications associated with impotence. RESULTS: We identified 1422 (1.4% of the male population over 16 years who might be expected to suffer from Erectile Dysfunction given an overall prevalence of 10%) who received a prescription forSildenafil Citrate (Viagra) over the study period at a cost of 0.14% of the annual drug budget. Up to 2.5%, 6% and 25% of patients were co-prescribed, respectively, nitrate therapy, potentially interacting drugs and drugs associated with impotence. CONCLUSION: The initial uptake and cost associated withSildenafil Citrate (Viagra) was lower than expected. The rate of prescribing of nitrates and other potentially interacting medications was found to be low. Medication use may also contribute to Erectile Dysfunction in this population of patients

Histopathological effects of Sildenafil Citrate (Viagra) on rat corpus cavernosum.

Sildenafil Citrate (Viagra) is widely used for the treatment of Erectile Dysfunction with various etiologies. The aim of the present study was the investigation of histopathological effects of Sildenafil Citrate (Viagra) on rat corpus cavernosum using tight and electron microscopical techniques. Twenty male rats were divided into two groups. The first group (n = 10) was used as a control and the second group (n = 10) was treated with Sildenafil Citrate (Viagra). Penile tissue was collected, fixed with formalin and embedded in paraffin for light microscopy, or fixed with gluteraldehyde and osmium tetroxide and embedded in Epon for electron microscopy. Light microscopical analysis showed that the corpus cavernosum was elongated and the number of blood vessels was increased. The amount of connective tissue in the penis was increased and dense collagen and smooth muscle fibers were observed in treated rats. Electron microscopical analysis showed that stromal structures of the corpus cavernosum (collagen fibers and number of cellular elements) were increased in treated rats. Fibroblasts showed signs of activation and the number of other stromal cells was increased. Immature newly synthesized collagen fibers were observed and penetrated endothelial basement membranes. In addition, endothelial cells also showed signs of activation such as cytoplasmic granules in treated rats, whereas the surface area of blood vessels was increased and basement membranes were thickened. These histopathological changes due to treatment with Sildenafil Citrate (Viagra) indicate that prolonged use of Sildenafil Citrate (Viagra) may increase the risk of fibrosis in the penis

Combination of phentolamine and L-arginine orSildenafil Citrate (Viagra) synergistically improves neurogenic relaxation of rabbit corpus cavernosum smooth muscle.

OBJECTIVES: To analyze the effects of combining an alpha-adrenergic receptor antagonist, phentolamine, with an enhancer of the nitric oxide/cyclic guanosine monophosphate pathway (L-arginine or sildenafil) on neurogenic relaxations of rabbit corpus cavernosum (RCC). METHODS: Studies were performed on isolated RCC tissue in organ chambers. Transmural electrical stimulation (TES) was applied at increasing frequencies (0.5 to 6 Hz) on endothelin-contracted RCC strips, and the responses were evaluated. RESULTS: The activation of alpha(2)-adrenergic receptors with UK 14304 (0.3 microM) significantly inhibited the relaxation induced by TES in RCC strips in which adrenergic neurotransmission was blocked with guanethidine (10 microM). The relaxant responses produced by TES application on RCC strips without guanethidine were not significantly affected by the treatment with L-arginine orSildenafil Citrate (Viagra) but were significantly augmented by phentolamine (2.7-fold increase in maximum relaxation). Furthermore, the combinations of phentolamine with L-arginine orSildenafil Citrate (Viagra) markedly increased the relaxations evoked by the application of TES in RCC tissue, significantly more than those obtained in the presence of phentolamine alone (4.5 or 4.7-fold increase of maximum relaxation, respectively). CONCLUSIONS: Our results demonstrated a synergistic interaction between the alpha-adrenergic blockade and the potentiation of the nitric oxide/cyclic guanosine monophosphate pathway to increase neurogenic relaxation of trabecular smooth muscle relaxation. This fact suggests that the combination of alpha-adrenergic receptor blockade with L-arginine orSildenafil Citrate (Viagra) could represent a therapeutic advantage in the treatment of Erectile Dysfunction

Prehospital consideration of sildenafil-nitrate interactions.

OBJECTIVE: To determine whether paramedics and on-line physicians screen patients for use of Sildenafil Citrate (Viagra) prior to prehospital administration of nitrates. METHODS: A prospective, observational study was performed over a one-month period in three EMS systems. Consecutive radio communications between on-line physicians and paramedics concerning male patients with cardiac complaints were monitored. Investigators observed the frequency with which on-line physicians screened forSildenafil Citrate (Viagra) use prior to ordering nitrates. After observation of the radio communications was completed, a written survey was distributed to all paramedics in the three EMS systems. RESULTS: Seventy-six physician-paramedic interactions were monitored. Nitrates were ordered by on-line physicians in 56 cases. No paramedic reportedSildenafil Citrate (Viagra) use/nonuse, and no on-line physician inquired about the patient's potential use of the drug. Only half of the surveyed paramedics reported that they routinely screen forSildenafil Citrate (Viagra) use, and approximately a fourth reported that its use would not alter their management of chest pain patients. CONCLUSION: In this study, on-line physicians in three EMS settings did not screen forSildenafil Citrate (Viagra) use prior to ordering nitrates. While some paramedics do screen forSildenafil Citrate (Viagra) use, practice patterns among paramedics in these three systems were inconsistent

Improvement in emotional well-being and relationships of users of sildenafil.

PURPOSE: We estimated the association ofSildenafil Citrate (Viagra) use with erectile function, relationship with sexual partner, functional status and emotional well-being in men with Erectile Dysfunction. MATERIALS AND METHODS: Letters were mailed to eligible patients at a university hospital urology and internal medicine clinic, and university affiliated community primary care clinics by the primary care provider or urologist inviting them to participate in the study. Of the eligible sample 124 men (53%) completed and returned a survey, including 85 who reported currentSildenafil Citrate (Viagra) use. Change scores in these patients were calculated using the International Index of Erectile Function, marital interaction scale from the Cancer Rehabilitation Evaluation System Short Form, 5-item emotional well-being scale of the RAND 36-Item Health Survey and 12-Item Short Form Health Survey. RESULTS:Sildenafil Citrate (Viagra) users reported an 88% increase in erectile function scores, 60% increase in overall sexual satisfaction and 36% increase in intercourse satisfaction related to the use ofSildenafil Citrate (Viagra) (p <0.001). Of the respondents 38% indicated that usingSildenafil Citrate (Viagra) had definitely improved quality of life. Likewise 29% of respondents indicated that usingSildenafil Citrate (Viagra) had definitely improved the relationship with their partner. WithSildenafil Citrate (Viagra) there was a statistically significant improvement in the scores of erectile and sexual function (p <0.001), sexual partner relationship (p = 0.007) and emotional well-being (p <0.001). In a multivariate model improved erectile function and sexual partner relationship were each significantly associated with improved emotional well-being (R2 = 0.20, p <0.001). CONCLUSIONS:Sildenafil Citrate (Viagra) users reported significant improvements in erectile and sexual function that were associated with positive changes in emotional well-being and the sexual partner relationships with their sexual partner