Effective Treatment For Erectile Dysfunction Research Articles

EFFECT OF SILDENAFIL CITRATE ON POST-RADICAL PROSTATECTOMY ERECTILE DYSFUNCTION

We assess the effect of sildenafil in a subgroup of patients after prostatectomy with erectile dysfunction and determine whether nerve preservation improves sildenafil response in this subgroup. Between April 1998 and January 1999, 53 patients who had undergone radical retropubic prostatectomy and were prescribed oral sildenafil were surveyed using a confidential mail questionnaire. Of the patients 21 underwent bilateral and 15 unilateral neurovascular bundle sparing procedures, while in 17 a nonnerve sparing procedure was performed. All patients received 25 to 100 mg. sildenafil in a flexible dose escalation manner. Response, satisfaction and side effects were assessed using a modified, self-administered International Index of Erectile Function questionnaire. Response was defined as erection sufficient for intercourse. Preoperative and postoperative/pretreatment erectile functions were assessed for baseline comparison in each patient, and partner overall satisfaction with sildenafil was measured. Statistical data analysis was performed using analysis of variance and Newman-Keuls multiple comparison tests. Of the 21 patients who underwent a bilateral nerve sparing procedure 15 had a positive response. Of the 15 patients who had undergone a unilateral nerve sparing procedure 12 had a positive response, and only 1 of the 17 patients who had undergone a nonnerve sparing procedure responded to sildenafil. The most commonly reported adverse events of all causes were headaches (21%), flushing (8.3%), visual disturbance (6.3%) and nasal congestion (6.3%). Sildenafil is an equally effective treatment for erectile dysfunction after bilateral and unilateral nerve sparing procedures, and patient response to sildenafil is confirmed by the partners. However, patients who undergo nonnerve sparing procedures do not respond satisfactorily to sildenafil.

Erectile dysfunction.

Erectile dysfunction (ED) is a common condition and can usually be managed pharmacologically, with drugs delivered by intracavernosal injection (ICI), transurethrally or orally. The cardiovascular status of the patient and his overall fitness for renewed sexual activity must be assessed before treatment for ED is initiated. The efficacy of sildenafil is related to the extent and severity of ED, and is significantly reduced in patients with severe vasculogenic ED, ED associated with diabetes and after radical prostatectomy. Alprostadil (prostaglandin E1) is the drug of first choice in patients treated with ICI; it is effective in 72.6% of men with ED and is associated with a low risk of priapism and cavernosal fibrosis. Transurethral alprostadil is significantly less effective than alprostadil ICI, producing improved erections in 30%-40%, but rigid erections in only 10%, of men with ED. There is Level II evidence that: alprostadil ICI is an effective treatment for ED papaverine ICI is associated with a high risk of cavernosal fibrosis and priapism papaverine ICI should be restricted to informed patients refractory to treatment with alprostadil ICI transurethral alprostadil is less effective than alprostadil ICI sildenafil is an effective treatment for ED.

SILDENAFIL CITRATE (VIAGRA®) IS EFFECTIVE AND WELL TOLERATED FOR TREATING ERECTILE DYSFUNCTION OF PSYCHOGENIC OR MIXED AETIOLOGY

SUMMARYSildenafil citrate (Viagra®) has been shown to be an effective treatment for erectile dysfunction (ED) of organic aetiology. This study assessed the efficacy and tolerability of sildenafil for treating ED of psychogenic and mixed psychogenic/organic aetiology. Men with ED of psychogenic and mixed aetiology were randomised in a double‐blind, fixed‐dose study to placebo (n=95) or sildenafil 10 mg (n=90), 25 mg (n=85), or 50 mg (n=81) once daily for 28 days. Efficacy was evaluated with two global efficacy questions, a patient log of erectile activity, a sexual function questionnaire and a partner questionnaire. Patients receiving sildenafil had significantly more grade 3 (hard enough for penetration) or grade 4 (fully hard) erections per week than patients receiving placebo, and a greater proportion of patients receiving sildenafil reported that treatment had improved their erections (p<0.001). Results of the sexual function questionnaire demonstrated significant improvement for patients with ED receiving sildenafil compared with patients receiving placebo for frequency, hardness and duration of erections (p<0.01), and for enjoyment of sexual intercourse and satisfaction with sex life (p<0.05). The results of the partner questionnaire were consistent with the results reported by patients and showed that treatment with sildenafil was associated with significant improvement in the partners' own sex lives (p<0.001). Adverse events were mostly mild to moderate in nature. The commonest adverse events were headache, dyspepsia, flushing, myalgia, arthralgia and flu syndrome. Discontinuations due to treatment‐related adverse events were few, ranging from 1.1% to 6.2% for patients receiving different doses of sildenafil and 4.2% for patients receiving placebo. Sildenafil is an effective and well‐tolerated treatment for ED of psychogenic or mixed aetiology with once‐daily dosing.

Side-effect profile of sildenafil citrate (Viagra) in clinical practice

Objectives. Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction. Initial studies reported a high tolerability and low incidence of certain characteristic adverse reactions. We sought to evaluate the incidence of side effects of sildenafil citrate, independent of industry support and constraints, utilizing a heterogeneous cohort of patients from a university-based practice. Methods. A prospective, open-label, flexible-dose study of 256 patients treated with sildenafil citrate for erectile dysfunction was performed at a single institution. The patients were questioned explicitly about the occurrence of headache, flushing, dyspepsia, nasal congestion, visual changes, and other side effects. Results. The adverse reactions most commonly observed were flushing (30.8%), headache (25.4%), nasal congestion (18.7%), and heartburn (10.5%). All events were short lived and mild in nature. In the present study, 31.6% of patients experienced one or more adverse events. However, no one withdrew from the study because of the severity of these events. There was a significant association between higher doses and the occurrence of side effects. Conclusions. The incidence of adverse events attributable to sildenafil citrate may be higher than initially reported, but an explanation may be the methodology of data collection and the industry-independent nature of this study. The side-effect profile is dose related and mild. Sildenafil citrate remains a safe and well-tolerated treatment for erectile dysfunction.

Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina

OBJECTIVEWe sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina.BACKGROUNDSildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs.METHODSTwo double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 μg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug.RESULTSThe effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, −52/−29 mm Hg) were greater than the effects of placebo plus ISMN on BP (−25/−15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (−36/−21 mm Hg) compared with placebo plus GTN (−26/−12 mm Hg; p < 0.01).CONCLUSIONSCoadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.

The use of sildenafil citrate for treatment of male infertility in males with erectile dysfunction

Objectives: Sildenafil Citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction (ED), resulting in erection and subsequent ejaculation. The objective of this study was to evaluate the quantitative and qualitative characteristics of ejaculates in men of reproductive age with ED undergoing infertility evaluation and employment of intrauterine insemination (IUI) for their wives.Materials and methods: A total of 3 patients with ED received Viagra and produced a total of 18 ejaculates for evaluation and sperm preparation for IUI. Each ejaculate was produced at intercourse via the use of the Male Factor Pak. Seminal specimens were assessed and processed via the ZSC-II method for IUI. Each processed specimen was evaluated for its appropriateness for IUI.Results: Sperm quantitative and qualitative measurements after production at intercourse were within normal range (WHO standards), and when specimens were processed for IUI, the sperm quantity and quality were adequate to cause conception. IUI specimens (0.7 mL) contained 23.5 ± 7.1 × 106 sperm/mL with 73.6 ± 6.8% motility and 3.3 ± 0.2 progressive motility (scale of 0–4).Conclusions: It appears that Viagra can be an effective tool for the treatment of reproductive age ED males undergoing infertility treatment in an IUI program. The ejaculates produced and the processed specimens for IUI were of adequate quality to establish a pregnancy in the treated couples.

Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro

Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), which has been shown to be a clinically effective treatment for erectile dysfunction. Its action results from increased levels of cyclic guanosine monophosphate (cGMP), which is normally degraded by PDE5. This cyclic nucleotide is a second messenger for nitric oxide, which is involved in the regulation of numerous functions, including vascular smooth muscle tone. In an attempt to better predict the effects of sildenafil on cardiovascular function, the distribution of PDE activity was determined with anti-PDE1 and anti-PDE5 antibodies in the human cardiac ventricle and saphenous vein, and in vitro studies were performed on the isolated human cardiac ventricle, corpus cavernosum, saphenous vein, and mesenteric artery as well as on rabbit aorta, dog coronary artery, dog trabecular tissue, and rabbit and human platelets. The major PDE activity in the human cardiac ventricle was shown to be calcium/calmodulin-dependent PDE1, but there was no detectable level of PDE5. In contrast, the human saphenous vein contained PDEs 1, 4, and 5, and the human mesenteric artery contained PDEs 1, 2, 3, 4, and 5. The distribution of PDE5 in the cardiovascular system is consistent with the observed pharmacodynamic and clinical effects of sildenafil. Sildenafil, unlike milrinone, a selective PDE3 inhibitor, had no effect on the isolated trabeculae carneae; this is consistent with the lack of PDE5 expression in cardiac myocytes. Sildenafil selectively increased cGMP levels in coronary vascular smooth muscle tissue but produced no change in cyclic adenosine monophosphate (cAMP) levels, which is consistent with the drug’s selectivity for PDE5. In phenylephrine-contracted isolated rabbit aortic rings, sildenafil enhanced the relaxation induced by the nitric oxide donor glyceryl trinitrate, suggesting that sildenafil may potentiate the hypotensive effects of nitric oxide donor agents on the vasculature, an effect that has been observed clinically. Human platelets were found to contain PDE5, which was inhibited by 50% (IC 50) by sildenafil at a concentration of 6.3 nM, consistent with the IC 50 value in the corpus cavernosum. Sildenafil alone had no direct effect on platelet function, but it potentiated the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human platelets. The pharmacodynamic and adverse event profiles observed in clinical trials with sildenafil are consistent with the in vitro profile of the tissue distribution of PDE5 and its known mechanism of action as a selective inhibitor of PDE5.

Sildenafil citrate and blood-pressure–lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)–cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 μg/min and doubling every 5 minutes to a maximum rate of 40 μg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 μg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were −8 mm Hg and −7 mm Hg, respectively (p ≤0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. Thus, no synergistic interaction was observed between sildenafil and the calcium antagonist amlodipine in patients with hypertension.

Overall cardiovascular profile of sildenafil citrate

Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the first in a new class of orally effective treatments for erectile dysfunction. During sexual stimulation, the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic circulation but at different points along the NO–cGMP pathway. The combination is contraindicated because they synergistically potentiate vasodilation and may cause excessive reductions in blood pressure. Erectile dysfunction is a significant medical condition that shares numerous risk factors with ischemic heart disease, and hence a substantial overlap exists between these patient groups. From extensive clinical trials, the most commonly reported cardiovascular adverse events in patients treated with sildenafil were headache (16%), flushing (10%), and dizziness (2%). The incidences of hypotension, orthostatic hypotension, and syncope and the rate of discontinuation of treatment due to adverse events were <2% and were the same in patients taking sildenafil and those taking placebo. Retrospective analysis of the concomitant use of antihypertensive medications (β blockers, α blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not indicate an increase in the reports of adverse events or significant episodes of hypotension compared with patients treated with sildenafil alone. In clinical trials, the incidence of serious cardiovascular adverse events, including stroke and myocardial infarction, was the same for patients treated with sildenafil or placebo. Concurrent disease states, such as renal or hepatic impairment, or concomitant use of inhibitors of the cytochrome P450 isozyme CYP3A4 could increase systemic exposure to sildenafil. Since the US market launch in April 1998, monitoring of spontaneous adverse event reports in association with sildenafil has demonstrated a pattern that is generally consistent with the experience observed during clinical development, with the exception of infrequent reports of priapism. In conclusion, extensive clinical testing has shown that overall treatment with sildenafil for up to 1 year is well tolerated and is associated with a low incidence of adverse events that result in discontinuation of treatment in <3% of patients.

Treatment of erectile dysfunction with sildenafil

Objectives. To determine the efficacy of sildenafil for the treatment of erectile dysfunction (ED) in a clinical practice setting; to evaluate the correlation between patient and partner perceptions of treatment outcomes; and to assess the relation between the severity of ED and response to treatment. Methods. Among the first 100 men to receive sildenafil in a urology practice setting, 74 (mean ± SD age 64 ± 11 years) completed a validated sexual function questionnaire (International Index of Erectile Function [IIEF]) before and after a 4 to 6-week treatment period. A modified version of the same questionnaire was independently completed by partners. ED was categorized into a severity class of I to IV. Results. Sildenafil treatment improved erections by 71% to 95%, according to responses in key IIEF questions 3 and 4. Overall, 57 (77%) of 74 patients desired to continue treatment after the test period. Patient score on the IIEF was correlated with partner score on the modified questionnaire before and after treatment ( r = 0.67 to 0.81, P <0.01). IIEF scores were reflected in a simple severity classification system. Men with the best preservation of erections (severity class I) exhibited the best responses to sildenafil, whereas men with no erections (severity class IV) were much less likely to respond to the drug and desire continuation of treatment ( P <0.01). Patients with a radical prostatectomy were relatively refractory to sildenafil, except for 2 of 5 who had undergone a nerve-sparing operation. Conclusions. In clinical practice, sildenafil is an effective treatment of ED, according to partner-validated questionnaire responses; and the results of treatment are predictable with an ED severity classification system.

Pharmacological profiles of sildenafil (VIAGRA) in the treatment of erectile dysfunction: efficacy and drug interaction with nitrate

Penile erection follows relaxation of the corpus cavernosum in which nitric oxide (NO) released during sexual stimulation from non-adrenergic non-cholinergic nerve endings and from endothelial cells of the corpus cavernosum plays a crucial role. Sildenafil (VIAGRA) selectively inhibited phosphodiesterase type 5 (PDE5) activity in the human corpus cavernosum and increased cGMP concentrations in the rabbit cavernosum in the presence of NO. Sildenafil enhanced the NO-dependent relaxation of the isolated human corpus cavernosum and the intracavernosal pressure in the anesthetized dog without affecting systemic blood pressure and heart rate. In the patients with erectile dysfunction, an orally administered sildenafil enhanced the penile rigidity during visual sexual stimulation. Sildenafil did not affect the phenylephrine-induced contraction of the isolated rabbit aorta, but enhanced the relaxant effect of glyceryl trinitrate. The pharmacodynamic interaction with glyceryl trinitrate was also observed in human studies where sildenafil potentiated the hypotensive effect of the nitrate. These results indicate that sildenafil, which enhances the physiological process of penile erection during sexual arousal, is a novel orally effective treatment for erectile dysfunction. It should be noted, however, that sildenafil enhanced the hypotensive effect of glyceryl trinitrate, as a result of inhibition of PDE5 in vascular smooth muscle. Therefore, administration of sildenafil to patients who are using nitrates and NO donors is contraindicated.

An investigation to compare the effect of short term, intensive speechtherapy and long term speechtherapy of patients suffering from Parkinson's disease

The ability to perform sexually and satisfy a partner is frequently perceived by men as defining their masculinity. Erectile dysfunction (ED) and loss of erection hardness can have a profoundly adverse effect on their psychological well-being. The loss of self-esteem associated with ED may, in turn, have an impact on their relationship with their sexual partner, which may result in a withdrawal from intimacy and of affection by their partner, leading to a vicious circle of behavioural change that may further compound the damage to the relationship and both partners psychological well-being. In some men, psychosocial distress caused by ED may develop into secondary depression, or it may aggravate depressive tendencies. This synergistic interaction between ED, depression, and physical illness means that a correct differential diagnosis is essential to target treatment on the leading cause of depression. Phosphodiesterase type 5 (PDE5) inhibitors have been used successfully to improve erection hardness in men with depression both alone and in combination with antidepressant therapy. Furthermore, recent prospective studies have demonstrated that by increasing erection hardness and the frequency of successful intercourse attempts, effective treatment of ED has positive effects on a man's psychological health and quality of sex life. The result is an increased desire for sexual intimacy that improves a man's relationship with his partner and overall life satisfaction.

The use of alprostadil sterile powder in a home self-injection study of Asian men with erectile dysfunction

This study evaluated the individual optimal dose of alprostadil in the office setting that could be used as the basis for effective home self-injection therapy. The study included 150 Asian men with erectile dysfunction (ED). The mean age of study participants was 48.3 years (range, 21 to 74 years), and the mean duration of ED was 3.6 years. The most common cause of ED was venogenic (24%), psychogenic (21%), arteriogenic (13%), neurogenic (0.7%), or a combination of these (41%). An optimal response was seen in 72% of patients (n = 108) in the office and 96% of patients (n = 100) at home. The mean ± SD office dose of alprostadil was 19.4 ± 12.8 μg versus 18.0 ± 12.2 μg at home. More than half of the patients (57% in an office setting and 53% at home) achieved an optimal response at a dose between 5 and 15 μg. By the 20-μg dose, 82% of patients had achieved an optimal dose at home compared with 70% of patients in the office. An optimal response was seen at the same dose in the office and home in 75% of patients; the dose at home decreased from the office dose for 16% of the patients and increased for 9%. There were 24 patients who experienced adverse events: penile pain after injection (18 patients), cold sweating (2 patients), pediculosis (1 patient), broken leg (1 patient), ankle pain (1 patient), and prolonged erection (1 patient). One patient discontinued the study because of penile pain. Alprostadil sterile powder offered safe and effective treatment of ED for home self-injection therapy. Once an optimal dose response had been established in the physician's office, further home adjustments were needed in 25% of patients. Penile pain, usually mild, was the most common, possibly related adverse effect reported.

Intracavernous prostaglandin E1 in erectile dysfunction.

Prostaglandin E1 (PGE1) is a naturally occurring substance that is present in a variety of mammalian tissues, including the semen of fertile men. Its use in the diagnosis and treatment of erectile dysfunction has been extensively studied. In doses of 10-20 micrograms, PGE1 produces full erections in 70-80% of patients with erectile dysfunction. In diagnostic use PGE1 is employed as a simple office test and in conjunction with various hemodynamic tests. Self-injection of PGE1, either with the patient or his partner administering the injection, is a minimally invasive and effective treatment for erectile dysfunction in patients with organic or psychogenic erectile dysfunction. Its use is contraindicated in patients with sickle cell anemia, severe coagulopathy, schizophrenia or severe psychiatric disorder, poor manual dexterity, severe venous incompetence, or severe systemic disease. As calculated from data in the published literature, the most frequent side effects are pain at the injection site or during erection (occurring in 16.8% of patients), hematoma/ecchymosis (1.5% of patients), and prolonged erection/priapism (1.3% of patients). The potential for prolonged erection/priapism, the most serious side effect, can be minimized by careful titration of the dose and through patient education. Systemic side effects occur rarely during PGE1 use. During extended use, patients should be monitored for potential long-term side effects, such as fibrosis and angulation.