Sildenafil in the Treatment of SSRI-Induced Sexual Dysfunction: A Pilot Study.

BACKGROUND: Sexual dysfunction is a well-documented side effect of selective serotonin reuptake inhibitors (SSRIs). Commonly reported side effects include erectile impotence, anorgasmia, ejaculatory delay, pain, loss of sensation, and decreased pleasure. Early reports of the reversal of sexual dysfunction after usingSildenafil Citrate (Viagra) in male and female patients receiving various types and dosages of SSRIs are promising and prompted this study. Our aim was to evaluate the effects of oralSildenafil Citrate (Viagra) on reported secondary sexual dysfunction in patients concurrently treated with SSRIs. METHOD: Fourteen male patients who developed sexual dysfunction while receiving SSRIs were screened using the Arizona Sexual Experience (ASEX) scale. An electrocardiogram was obtained at the beginning and at the end of the study. Each patient was prescribedSildenafil Citrate (Viagra) tablets to be taken twice a week, 25-100 mg, prior to sexual activity and told to record the findings in a running diary which he was to keep during his treatment period. The patients were seen weekly and evaluated by clinical interview and ASEX scale. Patients were treated for a total of 8 weeks. RESULTS: All but 1 of the 14 patients experienced an improvement of sexual dysfunction, with 9 patients at the first dose of 25 mg and 4 at higher doses (3 at 50 mg and 1 at 75 mg). One patient required 100 mg to obtain minimal response. DISCUSSION:Sildenafil Citrate (Viagra) was shown to be helpful in the treatment of SSRI-induced sexual dysfunction. Three patients continued to experience ongoing positive effects after discontinuation of sildenafil; the other 10 patients relapsed

Simultaneous assay ofSildenafil Citrate (Viagra) and desmethylsildenafil in human plasma using liquid chromatography-tandem mass spectrometry on silica column with aqueous-organic mobile phase.

A liquid chromatography-tandem mass spectrometry method was developed for the analysis ofSildenafil Citrate (Viagra) (SIL) and its metabolite desmethylsildenafil (DMS) in human plasma. Samples were accurately transferred to 96-well plates using a liquid handler (Multiprobe II). Solid-phase extraction was carried out on a 96-channel programmable liquid handling workstation (Quadra 96) using a C8 and cation-exchange mixed-mode sorbent. The extract was injected onto a silica column with an aqueous-organic mobile phase, a combination that was novel for improving the method sensitivity. The low limit of quantitation was 1.0 ng/ml for both SIL and DMS. The method was validated to meet the criteria of current industrial guidance for quantitative bioanalytical methods

Relaxation induced by cGMP phosphodiesterase inhibitorsSildenafil Citrate (Viagra) and zaprinast in human vessels.

BACKGROUND:Sildenafil Citrate (Viagra) is currently used in the treatment of Erectile Dysfunction. However, assessment of direct effects ofSildenafil Citrate (Viagra) on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects ofSildenafil Citrate (Viagra) on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison. METHODS: Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was recorded. Then the effects of sildenafil, zaprinast, and sodium nitroprusside on precontracted vessels were studied. RESULTS:Sildenafil Citrate (Viagra) (10(-8) - 3 x 10(-5) mol/L) caused concentration-dependent relaxation in the internal mammary arteries, radial arteries, and forearm veins. In the coronary arteries,Sildenafil Citrate (Viagra) had a modest relaxant effect. In addition,Sildenafil Citrate (Viagra) amplified the relaxation induced by sodium nitroprusside in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase NG-monomethyl-L-arginine (10(-4) mol/L). Compared with zaprinast,Sildenafil Citrate (Viagra) was eight to ten times more potent in terms of EC50 values. CONCLUSIONS: The direct relaxant effects ofSildenafil Citrate (Viagra) together with its synergistic interaction with nitric oxide donors should be considered in patients undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes

A comparison of radiation dose to the neurovascular bundles in men with and without prostate brachytherapy-induced Erectile Dysfunction.

PURPOSE: The etiology of Erectile Dysfunction after definitive local therapy for carcinoma of the prostate gland represents a multifactorial phenomenon including neurogenic compromise, venous insufficiency, local trauma, and psychogenic causes. It has been suggested that impotence after prostate brachytherapy is a consequence of excessive radiation dose to the neurovascular bundles (NVB). Herein we evaluate the potential relationship between radiation dose to the NVB and the development of Erectile Dysfunction following prostate brachytherapy. METHODS AND MATERIALS: The radiation dose to the NVB was evaluated for 33 patients who developed Erectile Dysfunction (ED) following brachytherapy plus 21 additional patients who were potent before and subsequent to brachytherapy. Of the 54 patient study group, the median follow up was 37 months, and 25 patients were managed with (125)I as a monotherapeutic approach and 29 received (103)Pd as a boost following 45 Gy of external beam radiation therapy. Radiographic localization of the NVB was performed via a two-dimensional geometric model that placed 3-NVB calculation points on the left and right posterolateral side of each 5-mm CT slice. Parameters evaluated included dose-surface histograms, dose parameters via point doses on each slice, the magnitude of the dose in relationship to the distance from the base, and the relationship between NVB radiation dose in patients with and without ED, patient response toSildenafil Citrate (Viagra) and case sequence number. RESULTS: In terms of percent prescribed minimum peripheral dose (% mPD), there was no significant difference in mean neurovascular bundle dose between potent and impotent patients, between the isotopes ((125)I or (103)Pd), mono- or boost therapy, or side of the prostate for which the overall average was 217% +/- 55% of mPD. There was also no significant dosimetric difference in terms of response toSildenafil Citrate (Viagra) based on a multivariate analysis which included % mPD and various dose thresholds and side of the gland. The dose distribution over the length of the prostate rose smoothly from the base and apex to peak at midgland in (125)I implants while (103)Pd implants had a relatively constant dose over the length of the prostate. Considering the calculation grid as forming a 6-mm wide ribbon along each side of the prostate, the average patient had 70 mm(2) area receiving at least 300% of mPD. CONCLUSION: In this study, no relationship between radiation dose to the NVB and the development of post brachytherapy Erectile Dysfunction was discernible. Such a difference may become evident with additional follow-up. If long-term brachytherapy-induced Erectile Dysfunction is related to the radiation dose to the NVB, the ultimate preservation of potency following prostate brachytherapy may be markedly inferior to what has been reported. Nevertheless, the majority of this patient population responded favorably toSildenafil Citrate (Viagra)

Post-marketing surveillance study of the safety and efficacy ofSildenafil Citrate (Viagra) prescribed in primary care to Erectile Dysfunction patients.

In order to investigate the safety and efficacy ofSildenafil Citrate (Viagra) prescribed in primary care, a post-marketing surveillance study was undertaken. A total of 651 men with Erectile Dysfunction (ED) were enrolled from 31 family physicians in Korea from December 1999 to July 2002. Patients were regularly followed up to ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled, 572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458 (80.1%) of 572 patients reported improved erectile function with sildenafil. Hypertension, diabetes and low-doseSildenafil Citrate (Viagra) were associated with poor efficacy. A total of 71 adverse events were reported among 56 patients (8.6%), with the most frequent being hot flushes (5.6%), followed by headache (2.6%), palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients (1.0%) discontinuedSildenafil Citrate (Viagra) as a direct result of adverse events. These results suggest thatSildenafil Citrate (Viagra) prescribed by primary care physicians was well tolerated and improved erectile function in patients with ED.International Journal of impotence Research (2005) 17, 71-75. doi:10.1038/sj.ijir.3901263 Published online 14 October 2004

Effect ofSildenafil Citrate (Viagra) on gastric emptying and postprandial frequency of antral contractions in healthy humans.

BACKGROUND:Sildenafil Citrate (Viagra) is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect ofSildenafil Citrate (Viagra) on gastric motor function after a meal was investigated in healthy humans. METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mgSildenafil Citrate (Viagra) (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed bySildenafil Citrate (Viagra) intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION: A single dose of 50 mgSildenafil Citrate (Viagra) does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers

Erectile function after brachytherapy with external beam radiation for prostate cancer.

The effect of therapeutic modalities on sexual potency is an important consideration for patients choosing a treatment for prostate cancer. We assessed erectile function after iridium-192 (1r-192) high-dose rate (HDR) brachytherapy with external beam radiation therapy (EBRT), and examined the efficacy ofSildenafil Citrate (Viagra) after this treatment. Forty-two prostate cancer patients (T1c to T3bN0M0) were treated with 22Gy HDR brachytherapy with 36.8Gy EBRT without neoadjuvant hormone therapy. Erectile function was assessed using a 5-item version of the International Index of Erectile Function questionnaire (IIEF-5), pre, 3 and 12 months after treatment, Potency was defined as an IIEF-5 score > or = 11. Ten patients with potency before HDR brachytherapy with EBRT with or without neoadjuvant hormone therapy requestedSildenafil Citrate (Viagra) 3 months after treatment. The mean IIEF-5 score of all patients was 10.5 +/- 8.5, 4.5 +/- 5.3 (p < 0.001), and 3.8 +/- 4.7 (p < 0.001), pre, 3 and 12 months after treatment, respectively. Seventeen (40.4%) patients were potent before treatment. The mean IIEF-5 score of those patients was 15.8 +/- 3.2, 9.6 +/- 5.1 (p = 0.04), and 11.3 +/- 6.1 (p = 0.06), pre, 3 and 12 months after treatment, respectively. Ten of 17 (58.8%) patients maintained their potency 12 months after treatment. In 10 patients with potency before treatment who were treated with sildenafil, the mean IIEF-5 score increased from 6.2 +/- 3.5 at 3 months to 13.6 +/- 5.1 (p < 0.001) at 12 months after treatment. Eight of 10 (80%) patients treated withSildenafil Citrate (Viagra) had recovered 12 months after treatment. HDR brachytherapy with EBRT can be performed with favorable results for maintaining potency

Relaxation and cGMP formation in response toSildenafil Citrate (Viagra) and sodium nitroprusside in saphenous veins from normotensive and hypertensive patients.

BACKGROUND: This study was designed to measure cyclic guanosine 3'5' monophosphate (cGMP) formation and relaxation response toSildenafil Citrate (Viagra) given either alone or in combination with sodium nitroprusside in saphenous veins obtained from normotensive and hypertensive patients. METHODS: Saphenous vein rings were obtained from 13 hypertensive and nine normotensive patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. The effect ofSildenafil Citrate (Viagra) on sodium nitroprusside-induced cGMP formation was also assessed. RESULTS:Sildenafil Citrate (Viagra) (10 nmol/L to 100 micromol/L) and sodium nitroprusside (0.01 to 100 nmol/L) caused concentration-dependent relaxations that were of greater magnitude in veins from normotensive patients.Sildenafil Citrate (Viagra) (1 to 10 micromol/L) amplified the relaxation induced by sodium nitroprusside in both groups of veins, but this effect was more pronounced in veins from hypertensive patients. Levels of cGMP in response to sodium nitroprusside were significantly lower in veins from hypertensive subjects. However, in the presence of sildenafil, the increase in cGMP levels in response to sodium nitroprusside was significantly greater in the hypertensive as compared with the normotensive group. CONCLUSIONS: Although the relaxant effects ofSildenafil Citrate (Viagra) are less pronounced in veins from hypertensive patients, the synergistic interaction sildenafil-sodium nitroprusside is more effective in veins from hypertensive patients, mainly due to an increase in cGMP accumulation