Sildenafil Citrate (Viagra): is there an influence on psychological performance?

BACKGROUND: Sildenafil Citrate (Viagra) is a well-introduced medicine for Erectile Dysfunction; many studies about effects and side effects are published. Beside these aspects of treatment the influence ofSildenafil Citrate (Viagra) on psychophysical performance is of interest. cGMP is one of the most important second messengers in the central nervous system (CNS), so even very small changes of the intracellular cGMP-level caused by phosphodiesterases inhibition may be relevant for CNS-function. We wanted to verify the hypothesis whether sildenfail influences human psychomotor performance, especially under the aspect of traffic safety, or not. METHODS: Designed as a pilot study we tested 6 male healthy volunteers using a test battery of 7 different psychophysical performances tests. Each individual did the test battery twice, once without drug and once after a single oral dose of 100-mg sildenafil. 3 persons did the first and 3 others did the second experiment under the influence of drug (UID). All results (37 parameters) were analysed by t-test for paired samples using a confidence interval of 95%. RESULTS: Only two parameters of 2 different tests showed significant differences. In the simple choice reaction test (DR2) the mean reaction time got better in the group with sildenafil; in the multiple choice reaction test with stress induction (RST3) the amount of wrong answers indicated a weak influence of performance without statistical significance, six parameters (dominantly in the speed anticipation test (DEST)) represented an increase and one other (RST3 second part) showed a decrease UID. The uppermost parameters (76% of all items) stayed on equal levels for both groups. CONCLUSION:Sildenafil Citrate (Viagra) showed no important impairment of psychophysical performance, no strong improvement was found as well. With a look at the therapeutically indication ofSildenafil Citrate (Viagra) the improvement in sexual activity may indicate no incapacity in traffic and other psychomotoric/psychophysical functions

Identification system forSildenafil Citrate (Viagra) in health foods

A substantially available identification system forSildenafil Citrate (Viagra) in health foods was established using 3 different analytical methods; i.e. TLC, preparative TLC/MS and HPLC/photo-diode array.Sildenafil Citrate (Viagra) in health foods was extracted with ethyl acetate under alkaline conditions as sample solutions for TLC and preparative TLC, and also extracted with 50% methanol and then diluted with solution of HPLC mobile phase for HPLC. The sample solution for TLC was applied to Silica gel 60 F254 plates with chloroform/methanol/28% ammonia (90:1:5, under layer) as mobile phase. Spots were located under UV radiation at 254 nm and 366 nm, and spraying dragendorff reagent. The conditions for preparative TLC were the same as these of TLC method, and samples abtained from preparative TLC were determined by MS with APCI interface, under both positive and negative modes. The HPLC analysis was carried out on a column of Cosmosil 5C18-AR (4.6 mm x 150 mm, 5 microns) with 0.05 mol/l phosphate buffer pH 3.0/acetonitrile(73:27) as mobile phase and the eluate was monitored by a photo-diode array detector. The quantitative analysis was available, when the peak of this sample on HPLC was detected at 290 nm. When this system was applied to commercial health foods,Sildenafil Citrate (Viagra) was identified and their contents were 25 mg-45 mg/tablet or bottle. These contents nearly correspond to that in Viagra, 25 mg, 50 mg/tablet. Therefore, there is a fear of side effects for Sildenafil, when it is taken as health foods

The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction.

Capacitation is the series of transformations that spermatozoa undergo in the female genital tract in order to bind to the zona pellucida, initiate the acrosome reaction, and fertilize an egg. Cyclic adenosine monophosphate (cAMP) plays an important role in this process and its levels are regulated by 2 key enzymes, adenylyl cyclase and cyclic nucleotide phosphodiesterase (PDE), the latter being involved in cAMP degradation. Evidence was provided for the involvement of PDE in sperm motility and capacitation. Of the 10 gene families of PDE that exist in mammalian tissues, the calcium-calmodulin-dependent (type 1) and the cAMP-specific (type 4) have been found in human spermatozoa. Using sildenafil, we investigated a highly potent cyclic guanosine monophosphate (cGMP)-specific PDE (type 5) inhibitor and whether this PDE is present in human spermatozoa and is involved in sperm functions.Sildenafil Citrate (Viagra) inhibited PDE activity of Percoll-washed spermatozoa with an IC50 of 97+/-3 and 33+/-3 microM when cAMP and cGMP, respectively, were used as substrates. Because the IC50 ofSildenafil Citrate (Viagra) obtained for PDE type 5 is much lower (2 to 6 nM) than that obtained with sperm PDE, the data suggest that PDE type 5 represents only a small fraction of the whole PDE activity of spermatozoa.Sildenafil Citrate (Viagra) causes dose-dependent increases in sperm cAMP levels and capacitation, which are associated with an increase in the levels of tyrosine phosphorylation of 2 fibrous sheath proteins (p105/81). Sperm velocity, amplitude of lateral head displacement, and hyperactivation were increased at 30-180 minutes.Sildenafil Citrate (Viagra) did not trigger the acrosome reaction in capacitated spermatozoa. These results suggest that under our experimental conditions,Sildenafil Citrate (Viagra) triggers human sperm motility and capacitation, probably via its inhibitory action on PDE activity other than type 5 with a resultant rise in cAMP levels

Sildenafil Citrate (Viagra) alleviates pulmonary hypertension after hypoxia and reoxygenation with cardiopulmonary bypass.

BACKGROUND: Sudden reoxygenation of hypoxic neonates undergoing cardiac operation exacerbates the systemic inflammatory response to cardiopulmonary bypass secondary to reoxygenation injury, worsening cardiopulmonary dysfunction. Reports suggestSildenafil Citrate (Viagra) decreases pulmonary hypertension and may affect myocardial function. Sildenafil's efficacy for treating postbypass cardiopulmonary dysfunction remains unknown. STUDY DESIGN: Fourteen neonatal piglets (5 to 7 kg) underwent 90 minutes of hypoxia, 60 minutes of reoxygenation with cardiopulmonary bypass, and 120 minutes of recovery. Six animals received 50 mg oralSildenafil Citrate (Viagra) and eight received saline at hypoxia. Data are presented as mean +/- SD. RESULTS:Sildenafil Citrate (Viagra) prevented the high pulmonary vascular resistance observed in controls (controls baseline 81 +/- 37 dynes. s/cm(5) versus recovery 230 +/- 93 dynes. s/cm(5), p = 0.004;Sildenafil Citrate (Viagra) baseline 38 +/- 17 dynes. s/cm(5) versus recovery 101 +/- 60 dynes. s/cm(5), p = 0.003). Despite lower pulmonary vascular resistance after sildenafil, arterial endothelin-1 (ET-1) was increased in both groups (control baseline 1.3 +/- 0.5 pg/mL versus recovery 4.5 +/- 3.7 pg/mL, p = 0.01;Sildenafil Citrate (Viagra) baseline 1.3 +/- 0.3 pg/mL versus recovery 9.8 +/- 4.9 pg/mL, p = 0.003). Intravenous nitric oxide (NO) levels were preserved afterSildenafil Citrate (Viagra) treatment (sildenafil baseline 340 +/- 77 nM versus recovery 394 +/- 85 nM). IV NO levels in controls were decreased when compared with baseline (control baseline 364 +/- 83 nM versus recovery 257 +/- 97 nM, p = 0.028). Although levels of exhaled NO decreased in both groups, the sildenafil-treated animals had higher levels of exhaled NO when compared with controls at the end of recovery (0.6 +/- 0.4 parts per billion versus 1.8 +/- 0.9 parts per billion, respectively, p = 0.029). CONCLUSIONS:Sildenafil Citrate (Viagra) alleviated pulmonary hypertension after reoxygenation with cardiopulmonary bypass. Despite increased ET-1 levels, pulmonary vascular resistance was lower withSildenafil Citrate (Viagra) treatment, suggesting sildenafil's effect on the pulmonary vasculature is capable of countering vasoconstriction by ET-1. Further study into the role ofSildenafil Citrate (Viagra) in perioperative therapy and its interactions with ET-1 are warranted

Sildenafil induces retinal vasodilatation in healthy subjects.

BACKGROUND: The cardiovascular effects of Sildenafil Citrate (Viagra), a selective inhibitor of phosphodiesterase type 5 (PDE5), have been extensively studied. However, its effect on human retinal arteries and veins has not yet been investigated. The effect of a single dose administration ofSildenafil Citrate (Viagra) on the retinal vessel diameters of healthy subjects was evaluated. METHODS:Sildenafil Citrate (Viagra) 50 mg was administered to 10 healthy subjects (male:female = 4:6; mean age 31 (SD 6) years). The diameters of retinal arteries and veins were measured by means of a retinal vessel analyser (RVA) immediately before and at 30, 60, 90, and 120 minutes afterSildenafil Citrate (Viagra) uptake. Blood pressure, heart rate, and intraocular pressure were monitored in parallel. RESULTS: A significant increase of 5.8% (p<0.001) in both retinal arterial and venous diameters was found 30 minutes afterSildenafil Citrate (Viagra) uptake. The diameters returned to baseline after 120 minutes. A mild systemic hypotensive response was seen. Changes in heart rate and intraocular pressure were not observed. CONCLUSION:Sildenafil Citrate (Viagra) causes a significant dilatation of retinal arteries and veins in healthy subjects. A possible role for PDE5 in the regulation of retinal blood flow is implicated



Cardiovascular parameter changes in patients with Erectile Dysfunction using pde-5 inhibitors: a study withSildenafil Citrate (Viagra) and vardenafil.

Sildenafil is the most prescribed oral agent for patients with Erectile Dysfunction (ED). Vardenafil is a new phosphodiesterase type 5 (Pde-5) inhibitor that was approved by the US Food and Drug Administration last year to treat patients with ED of various causes. Both of these Pde-5 inhibitors have vasodilating properties and effects on blood pressure (BP), and like nitrates, they work through the nitric oxide cyclic guanosine monophosphate pathway. The aim of this study was to investigate the influence of these Pde-5 inhibitors on BP and heart rate (HR) in normotensive men with ED by a crossover comparison. Thirty-five patients with ED were enrolled to evaluate and compare the effect ofSildenafil Citrate (Viagra) (50 mg) and vardenafil (10 mg) on BP and HR. At the screening (baseline [B]) visit, sitting systolic blood pressure (B-SBP), diastolic blood pressure (B-DBP), and HR were measured. We performed a multiple administration for both drugs and, therefore, multiple measurements of BP and HR changes, 3 doses a week, on alternate days, late in the afternoon, and on an empty stomach. B-SBP, B-DBP, and HR were recorded before each 50-mgSildenafil Citrate (Viagra) dosing and after 30, 60, 120, and 240 minutes. Data were averaged over the 4 time points and compared with the baseline values obtained before each dosing. After a 3-week wash-out period, patients were crossed over to vardenafil (10 mg) with the same study design. After administration of both drugs, we observed a statistically significant decrease of BP and an increase of HR. On average,Sildenafil Citrate (Viagra) caused a decrease of SBP ranging from 5.1 +/- 3.9 mm Hg during the first dosing to 4.7 +/- 4.2 mm Hg during the third dosing, DBP ranged from 4.4 +/- 4.9 to 4 +/- 4.1 mm Hg, and HR increased 1.8 +/- 2.0 bpm (first dose) and 1.2 +/- 0.9 bpm (third dose). With vardenafil, we recorded a greater variation for SBP and DBP. SBP decreased from 8.02 +/- 8.0 mm Hg during the first dosing to 5.4 +/- 5.5 mm Hg during the third dosing, whereas DBP decreased from 6.6 +/- 7.2 to 5.0 +/- 5.3 mm Hg, respectively. Recorded HR showed an increase of 3.1 +/- 3.2 bpm (first dose) and 2.4 +/- 2.3 bpm (third dose). After the first vardenafil administration, we recorded fainting episodes in 3 patients because of a decrease in BP greater than 20 mm Hg. Two of the patients were in therapy with doxazosin for benign prostatic hyperplasia (BPH). Cardiovascular response was not significantly different after the first dose between the 2 treatments. Vardenafil demonstrated clinically significant differences (fainting) with respect toSildenafil Citrate (Viagra) only during the first doses. We suggest that before starting therapies with Pde-5 inhibitors, particularly with the newer ones, that baseline cardiovascular parameters are measured and monitored, especially during the first dose, because of the presence of a "first dose effect." Moreover, it is necessary to pay particular attention to those patients in treatment with other drugs that could have a synergistic hypotensive effect as a result of vasodilation potentiation

Long-term intracavernous therapy responders can potentially switch to Sildenafil Citrate (Viagra) after radical prostatectomy.

OBJECTIVES: To assess whether long-term users of intracavernous (IC) injections after radical prostatectomy can switch to oral therapy with Sildenafil Citrate (Viagra). METHODS: Forty-nine patients (mean age 60.9 years) with Erectile Dysfunction after radical prostatectomy were identified as long-term users of IC injections (3.7 +/- 1.9 years). These patients received open-label treatment with Sildenafil Citrate (Viagra) (50 to 100 mg) for a minimum of 4 weeks or five attempts. The primary outcome measure of our study was assessed by the Sexual Health Inventory of Men (SHIM) questionnaire (International Index of Erectile Function-5 [IIEF]). A successful switch was prospectively defined as erection sufficient for vaginal penetration afterSildenafil Citrate (Viagra) use and compliance to therapy. Patients were designated as responders or nonresponders on the basis of their ability to achieve vaginal penetration. RESULTS: Of 49 patients, only 36 agreed to receive oral open-labelSildenafil Citrate (Viagra) (50 to 100 mg) for a minimum of 4 weeks or five attempts. Prostaglandin E1 (PGE1) was used in 70% and triple therapy (PGE1, papaverine, and phentolamine) in the remaining 30%. Of the 36 patients, 15 (41%) successfully switched toSildenafil Citrate (Viagra) and discontinued IC injections. When the results were stratified by the type of IC solution, patients with high-dose triple therapy had a poor success rate of switch (7%) compared with patients using PGE1 treatment (67%). Of the 36 patients, 14 (38%) foundSildenafil Citrate (Viagra) ineffective and continued using IC injections. Patients who switched to oral therapy had had a greater (P <0.001) total mean SHIM (IIEF-5) score with IC injections than those who did not switch (12.3 +/- 7.8 versus 20.0 +/- 4.9). Of the 36 patients, 7 (19%) foundSildenafil Citrate (Viagra) alone to be suboptimal but continued using it, enhancing the efficacy of IC injections alone. The three predictive factors for a successful switch were high preoperative SHIM (IIEF-5) score, high post-IC injection SHIM score, and type of IC medication used (PGE1 alone versus high-dose triple therapy). CONCLUSIONS: Long-term users of IC injection therapy can potentially switch to Sildenafil Citrate (Viagra) with acceptable sexual satisfaction. Patients will accept a lower degree of sexual satisfaction as measured by the IIEF-5 (SHIM) score if oral therapy is effective