Effects ofSildenafil Citrate (Viagra) on cAMP and cGMP levels in isolated human cavernous and cardiac tissue.

OBJECTIVES: To further investigate the mechanism of action of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5 (PDE5), that has been proved to be effective in the treatment of male Erectile Dysfunction. We assessed the effects ofSildenafil Citrate (Viagra) on the in vitro formation of cGMP and cyclic adenosine monophosphate (cAMP) in isolated human corpus cavernosum and cardiac muscle. METHODS: Isolated segments of human corpus cavernosum and cardiac muscle were exposed to increasing concentrations of sildenafil. The dose-dependent accumulation of cGMP and cAMP was determined in the tissue samples by means of radioimmunoassays. Responses of the isolated tissue preparations toSildenafil Citrate (Viagra) were compared with those obtained with the reference compounds sodium nitroprusside, forskolin, and milrinone. RESULTS: In the concentration range 0.01 to 1 microM, there was only a minor effect ofSildenafil Citrate (Viagra) on cGMP levels in isolated human cavernous and cardiac tissues. In contrast,Sildenafil Citrate (Viagra) was found to increase cAMP significantly in both cavernous and cardiac tissue in physiologic and supraphysiologic concentrations. The stimulation of cAMP bySildenafil Citrate (Viagra) was more pronounced in cavernous than in cardiac tissue. Concentrations of cGMP in the cardiac strips were unaltered by milrinone; cAMP was stimulated starting at a concentration of 0.05 microM. In the range of 0.1 to 1.0 microM, the in vitro effect ofSildenafil Citrate (Viagra) on cAMP levels in the cardiac samples was almost equivalent to that of milrinone. CONCLUSIONS: Our findings provide a potential mechanism for the cardiovascular side effects that have been reported withSildenafil Citrate (Viagra) use, highlighting the fact that a "cross-talk" between cGMP and cAMP-dependent signal transduction pathways might exist in human cavernous and cardiac muscle that may be of pharmacologic significance

Sildenafil test: changes in the diagnostic and therapeutic management of Erectile Dysfunction.

OBJECTIVE: To assess the efficacy ofSildenafil Citrate (Viagra) as a first-step diagnostic and therapeutic tool for Erectile Dysfunction (ED) and to evaluate the consequent changes in the management of male sexual insufficiency. MATERIALS AND METHODS:Sildenafil Citrate (Viagra) in titrating doses up to 100 mg was prescribed to 50 men presenting to a sexual dysfunction clinic with medically documented ED. They had not undergone any specific diagnostic test before starting sildenafil. RESULTS: Of the 50 men, 24 (48%) responded to sildenafil. Of these, 8 (33.3%) responded to 50 mg and 16 (66.7%) to 100 mg of sildenafil. Of the responders, 9 representing 18% of all studied men were discharged achieving spontaneous erections in a mean follow-up of 5.3 months. Men with no medical history, men with hypertension and men with mild coronary artery disease responded better. CONCLUSIONS: TheSildenafil Citrate (Viagra) test revealed that 48% of men responded to this therapy with no requirement for more invasive tests and that 18% of men required no further treatment at all. In addition this test reduced the overall cost of the diagnostic investigation. It is proposed that theSildenafil Citrate (Viagra) test should be used in cases with no significant medical history or in men with hypertension or mild coronary artery disease although almost all men with ED could be categorized as sildenafil-responders or sildenafil-resistant. It is also suggested that theSildenafil Citrate (Viagra) test would result in the ability for more men with ED to be managed exclusively in the primary care sector

Efficacy and safety ofSildenafil Citrate (Viagra) for treating Erectile Dysfunction in patients on dialysis.

OBJECTIVE: To assess the efficacy ofSildenafil Citrate (Viagra) for Erectile Dysfunction (ED) in patients on haemodialysis (HD) or peritoneal dialysis (PD), as men with end-stage renal disease (ESRD) often have sexual dysfunction (up to 82% among those on chronic dialysis). PATIENTS AND METHODS: Forty-one patients with ED and in ESRD participated in an open-label prospective study. Thirty patients on HD and 11 on PD were asked to complete the International Index of Erectile Function (IIEF) and Fugl-Meyer life-satisfaction scale before and afterSildenafil Citrate (Viagra) treatment. A total score in the erectile function domain of < or = 25 was accepted as indicating ED. All patients were started on a 25-mg dose, which was increased to 50 mg if there was no response after two trials. In addition, the overall efficacy question was used to evaluate satisfaction, and patients reported any side-effects during treatment. RESULTS: The erectile function and intercourse satisfaction domains improved significantly in both groups (P < 0.01). AfterSildenafil Citrate (Viagra) treatment, two-thirds of those on HD (20/30) and nine of the 11 on PD recovered their erectile function. The pretreatment scores on the IIEF and four domains (except sexual desire) of those responding were significantly higher than in those not responding (P < 0.05). The satisfaction rate on the overall efficacy question was 80% and 82% for the HD and PD groups, respectively. At least one side-effect was seen in 17 patients (43%); one had severe hypotension in the PD group. Overall, mild headache (seven patients, 18%) and flushing (12, 30%) were reported most often. CONCLUSIONS:Sildenafil Citrate (Viagra) is a safe and satisfactory drug for improving erectile function in patients with ESRD. Patients were satisfied whether treated by HD or PD. Pretreatment scores on the IIEF may be useful for predicting the success of treatment

Clinical efficacy and safety of Sildenafil Citrate (Viagra) in a multi-racial population in Singapore: A retrospective study of 1520 patients.

BACKGROUND: Sildenafil Citrate (Viagra) (Viagra), a selective inhibitor of cGMP-specific phosphodiesterase type-5, has been used as an oral therapeutic drug for Erectile Dysfunction. The present paper is a clinical study of the success rate and side-effects of the use ofSildenafil Citrate (Viagra) in a multi-racial population in Singapore. METHODS: From April 1999 to May 2000, 1520 patients were given Sildenafil Citrate (Viagra). Of these, 912 patients (mean age, 54.6 years; age range, 22-99 years) were followed up and evaluated for clinical efficacy and safety of the drug. The mean duration of Erectile Dysfunction (ED) and follow-up periods were 31.5 and 3.0 months, respectively. RESULTS: Satisfactory erections assessed by single global efficacy question (GEQ) occurred in 83% of patients, major side-effects in the form of flushing (3.48%), headache (1.97%), blurred vision (1.25%), giddiness (1.18%), warmth (1.11%) and others (4.92%) were recorded in 127 patients (13.9%). Racially, Chinese men with ED had higher efficacy (85.7%), compared to Indian men (74.2%) and Malay men (72.8%). With respect to comorbid profiles, an efficacy of 77.8% (n = 271), 83.9% (n = 292), 86.4% (n = 44) and 83.3% (n = 199) was recorded in diabetic, hypertensive, ischemic heart disease patients and in benign prostatic hyperplasia patients, respectively. Patients who smoked (n = 135) and drank alcohol (n = 118) showed an efficacy of 80%. Baseline hormonal profiles of luteinizing hormone, follicle stimulating hormone, testosterone and prolactin did not affect the success rates of Sildenafil Citrate (Viagra). Many patients had earlier received other forms of treatment (medicated urethral suppository for erection (MUSE; 84.9%); vacuum devices (86.8%), traditional medicines (100%) and other oral medications (89.2%)), but this did not influence the success rate of Sildenafil Citrate (Viagra). But patients previously treated with prostaglandin-E intracavernosal injections were less successful on Sildenafil Citrate (Viagra) (77.3%). In the total cohort, 50 mg Sildenafil Citrate (Viagra) was an effective dose in 49% of patients and 46.5% patients needed 100 mg Sildenafil Citrate (Viagra), while 4.1% of the total cohort needed only 25 mg Sildenafil Citrate (Viagra). CONCLUSION: Oral Sildenafil Citrate (Viagra) has been shown to be an effective, safe and well tolerated drug in Singaporean men with ED, as in men from other parts of the world

Effects of two selective phosphodiesterase type 5 inhibitors,Sildenafil Citrate (Viagra) and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat.

The present study investigated the effects of two cyclic GMP-specific phosphodiesterase enzyme type 5 inhibitors,Sildenafil Citrate (Viagra) and vardenafil, on the memory performance in the object recognition task. Both compounds were given per orally (1, 3 and 10 mg/kg sildenafil; 0.1, 0.3, 1 and 3 mg/kg vardenafil) immediately after the exposure to two identical objects. The memory for the objects was tested 24 h later. Vehicle-treated rats spent equal times exploring a new and the familiar object demonstrating that they did not remember the familiar one. However,Sildenafil Citrate (Viagra) improved the object discrimination performance of the rats with a high discrimination performance at a dose of 3 mg/kg. Rats treated with vardenafil also showed an improved object discrimination performance. Compared with sildenafil, vardenafil appeared to be even more potent in this respect since it already produced a high discrimination performance at a dose of 0.3 mg/kg. The effects of both compounds on cyclic GMP and cyclic AMP accumulation were studied in rat hippocampal slices incubated in vitro. Cyclic GMP levels were increased after incubation with the highest concentration of 100 microM vardenafil (together with 0.1 mM sodium nitroprusside), although no changes in cyclic GMP levels were detected after incubation with different concentrations of sildenafil. Both compounds had no effect on cyclic AMP levels. Additional cyclic GMP immunocytochemistry showed that incubation with vardenafil (in the presence of sodium nitroprusside) resulted in a concentration-dependent staining of cyclic GMP. Staining was predominantly found in neuronal fibres in the hippocampal CA2/CA3 region. It was already detected at a concentration of 0.1 microM vardenafil. Also positive fibres were detected after incubation withSildenafil Citrate (Viagra) but at a higher concentration of 10 microM. Taken together, these results suggest that inhibition of phosphodiesterase enzyme type 5 improves object recognition memory. This effect might be explained by increased levels of central cyclic GMP.

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

Management of Erectile Dysfunction by combination therapy with testosterone andSildenafil Citrate (Viagra) in recipients of high-dose therapy for haematological malignancies.

Erectile Dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg ofSildenafil Citrate (Viagra) orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant

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