Prednisolone or pentoxifylline for alcoholic hepatitis.

BACKGROUND: Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. METHODS: We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline. RESULTS: A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002). CONCLUSIONS: Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).

Noninvasive assessment of acute cardiopulmonary effects of an oral single dose of sildenafil in patients with idiopathic pulmonary hypertension.

We aimed to assess the acute cardiopulmonary effects of a 100-mg oral single dose of sildenafil in patients with idiopathic pulmonary hypertension (IPAH) using a well-validated but less-used noninvasive echocardiographic method for the measurement of both systolic and diastolic pulmonary artery pressure (PAP), by tricuspid regurgitation (TR) velocity curve analysis. We studied 12 consecutive patients with IPAH (10 patients with New York Heart Association functional class III, and 2 patients with functional class II). A 100-mg oral single dose of sildenafil was added to previous medications of all patients and its immediate effects were evaluated 1, 5, and 12 h after treatment. Using paired analysis, administration of a 100-mg oral single dose of sildenafil led to a significant reduction in mean PAP and a remarkable increase in pulmonary acceleration time (PAT) 1 h after treatment (P = 0.000; 95% confidence interval [CI] 18.99-26.00 and P = 0.005; 95% CI -12.89 to -2.95, respectively). In addition, although the right heart dimensions (right atrium and right ventricle) showed a trend toward improvement, the differences were not statistically significant (P = 0.13 and P = 0.08, respectively). Our results demonstrated that Doppler examination of TR alone can be easily used for the estimate of systolic and diastolic PAP in patients with IPAH. This study also shows that sildenafil is the only drug given orally that can evaluate the vasodilatory capacity of the pulmonary vascular bed in patients with IPAH, with promising effects on mPAP and PAT in these patients.

Assessment of the acute effects of tadalafil on the cardiovascular system based on examination of serum oxidative status and paraoxonase activity in men with erectile dysfunction: a preliminary study.

Phosphodiesterase type 5 inhibitors were initially approved for the treatment of erectile dysfunction in men and were later suggested for some systemic disorders, mostly due to their possible beneficial effects on endothelial functions. Paradoxically, though, phosphodiesterase type 5 inhibitors may have some life-threatening effects, for which there is weak evidence, it appears that they are associated with cardiovascular problems such as myocardial infarction and stroke. This study aimed to investigate the acute effects of tadalafil citrate on the cardiovascular system by evaluating serum oxidative status and paraoxonase-1 activity. Sera of 36 patients with erectile dysfunction were analyzed for total antioxidant status, total oxidant status and paraoxonase-1, before and after the administration of tadalafil citrate. Pre- and post-tadalafil citrate serum levels of total antioxidants, total oxidants and paraoxonase-1 were 1.1+/-0.0 and 1.6+/-0.0 micromol H(2)O(2) equiv l(-1), 10.3+/-1.1 and 6.9+/-1.2 micromol H(2)O(2) equiv l(-1), and 111.6+/-17.8 and 168.0+/-18.1 U l(-1), respectively (P<0.0001 for all results). This preliminary study confirmed that tadalafil citrate exerts a beneficial acute effect on the cardiovascular system by reducing serum levels of oxidative stress and increasing serum levels of paraoxonase-1.

[Erectile dysfunction after radical prostatectomy : patient information, contact persons, postoperative proerectile therapy]. / Erektile Dysfunktion nach radikaler Prostatektomie : Aufklärung, Ansprechpartner, postoperative proerektile Therapie.

BACKGROUND: Postoperative erectile dysfunction (ED) is one of the potential after-effects of radical prostatectomy. The aim of this study was to learn which caregivers inform the patients prior to the intervention about the risk of ED, which individuals the patients discuss this issue with, and whether the patients preoperatively consider use of a PDE5 inhibitor for proerectile therapy after the operation. METHODS: Using the IIEF-5 questionnaire, the preoperative erectile function of 110 patients was evaluated after the hospital admission interview. The patients were asked who had informed them about the risk of postoperative ED. They were also asked in whom they had confided to discuss this issue and whether they were prepared to undergo postoperative proerectile therapy with a PDE5 inhibitor. The patients were subsequently assigned to one of two groups: group I, consisting of those with a preoperative IIEF score > or = 21, or group II, those with a preoperative IIEF score <21. RESULTS: The answers given by groups I and II did not differ significantly. The median patient age was the same, 68, in both groups. In addition to being informed about postoperative ED by the hospital doctor on admission (100%), the patients were informed about this by the following individuals (results for group II in parentheses): board-certified urologist, 81.8% (74%); general practitioner (GP), 27.3%; partner, 12.1% (11.7%); self-help groups, 0% (2.6%); and friends, 3% (6.5%). Patients also discussed the risk of postoperative ED with the following individuals (results for group II in parentheses): local urologist, 66.7% (63.4%); partner, 45.5% (42.9%); hospital doctor, 39.4% (42.9%); GP, 21.2% (23.4%); friends, 9.1% (14.3); or no one, 3% (5.2%). Regarding whether patients were willing to undergo postoperative therapy using a PDE5 inhibitor, 36.4% in group I and 32.5% in group II said yes, 12.1% in group I and 11.7% in group II said no, and 51.5% in group I and 55.8% in group II were undecided. CONCLUSION: Irrespective of the patient's erectile status, the hospital doctor and the local urologist informed the patients about the risk of postoperative ED. Satisfactory information delivered by at least two people occurred in over 70% of all cases. The most frequent confidant of the patient for discussing this issue was his local urologist. Fewer than 50% of the patients discussed this topic with their partners. Possible reasons for underestimating the importance of sexual function could be the frequent taboo status of sexuality as a discussion topic in relationships, as well as preoperative distress. These circumstances should be taken into account by offering sufficient information, including that on the availability of postoperative proerectile therapy, for both the patient and his partner as early as possible, i.e., at the stage of choosing a treatment option.

The potential role of roflumilast: the new phosphodiesterase-4 inhibitor.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of roflumilast in the treatment of asthma and chronic obstructive pulmonary disease (COPD). DATA SOURCES: Studies, review articles, and meeting abstracts evaluating roflumilast were obtained from MEDLINE (1966-May 16, 2006), EMBASE (1980-May 16, 2006), and International Pharmaceutical Abstracts (1970-May 16, 2006) databases. Key terms used in all of the database searches were roflumilast, phosphodiesterase-4 inhibitor, asthma, chronic obstructive pulmonary disease, and COPD. Company Web sites were reviewed, and bibliographies of selected articles were evaluated for pertinent articles. STUDY SELECTION AND DATA EXTRACTION: In vitro, in vivo, and animal studies were selected, as were published human studies on the efficacy and safety of roflumilast. Due to limited published data on its safety, efficacy, pharmacokinetics, and drug interactions, meeting abstracts were also selected. Data retrieved from abstracts only is indicated in the references. DATA SYNTHESIS: Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor which, due to its selective inhibition of the PDE 4 isoenzyme, has potential antiinflammatory and antimodulatory effects in the pulmonary system. It has been studied as an oral tablet in doses of 250 or 500 microg/day. Animal data and clinical trials have demonstrated roflumilast's efficacy and safety as an antiinflammatory and antimodulatory agent for use in asthma and COPD, with no documented drug interactions and a favorable adverse effect profile. CONCLUSIONS: Roflumilast may be an additional option in the treatment of asthma and COPD due to its ease of administration and a seemingly favorable adverse event profile. However, more research is needed to solidify roflumilast's place in therapy.

Utilization and cost of sildenafil in a large managed care organization with a quantity limit on sildenafil.

OBJECTIVE: Erectile dysfunction (ED) affects approximately 30 million men in the United States. The objectives of this study were to (1) assess the cost and utilization of sildenafil citrate (Viagra), an oral therapeutic agent for ED, in a large managed care organization (MCO) with a quantity limit of 6 units per 30-day supply and (2) describe the incidence of comorbid conditions and the severity of cardiovascular disease in adult male users of sildenafil. METHODS: Pharmacy claims for sildenafil were identified from an administrative database of claims with dates of service in calendar year 2001 for male members aged 18 years or older. Medical claims for MCO members who had sildenafil claims were used to identify comorbid diseases and categorize patients by degree of cardiovascular risk. High risk was defined as having at least 1 medical claim with a diagnosis of diabetes mellitus, ischemic heart disease, abdominal aortic aneurysm, or peripheral arterial disease, and medium risk was defined as not having any diagnosis in the high-risk category but at least 1 cardiovascular risk factor that included smoking, hypertension, hypercholesterolemia, family history of premature coronary heart disease, or being aged 45 years or older. RESULTS: There were 67,914 pharmacy claims for sildenafil during 2001 for 20,281 MCO members, an average of 3.3 pharmacy claims per patient. The prevalence of sildenafil use was 54.1 per 1,000 male MCO members aged 18 years or older. The total allowed charges for sildenafil pharmacy claims in 2001 were 3.56 million US dollars, of which patients paid 26.6% in average cost-share, and the net MCO cost per member per month (PMPM) was 0.18 US dollars. A total of 1,681 patients (8.3%) exceeded their quantity restrictions for sildenafil tablets in 2001, of which 1,362 (81.0%) paid cash and 319 (19.0%, or 1.6% of all sildenafil users) appealed and received approval from the MCO for additional sildenafil tablets beyond the restriction of 6 tablets per month. Medical claims were available for 15,644 sildenafil patients (77.1%), and 12,720 sildenafil users (81.3% of those with medical claims) were judged to be at high or medium cardiovascular risk. CONCLUSIONS: A quantity limit of 6 tablets of sildenafil per 30-day period was associated with a drug cost to users and the MCO of 0.25 US dollars PMPM. Sildenafil users paid an average cost-share of 26.6%, resulting in a net drug cost of 0.18 US dollars PMPM to the MCO.

Why do patients with erectile dysfunction abandon effective therapy with sildenafil (Viagra)?

This prospective study determined the rate of abandonment of sildenafil therapy and assessed the reasons for abandonment. Between January 2001 and December 2002, 234 patients with erectile dysfunction (ED) at three independent centers successfully began therapy with sildenafil 50 or 100 mg. The rate of noncompliance was 31%. A telephone survey of these patients was conducted to determine the reasons for abandonment. The majority reported that they had had no opportunity or desire for sexual intercourse or that their partners had shown no sexual interest. Few patients stated that the high cost of the medication or that adverse events were the cause.

Pentoxifylline (PTX)--an alternative treatment in Graves' ophthalmopathy (inactive phase): assessment by a disease specific quality of life questionnaire and by exophthalmometry in a prospective randomized trial.

PURPOSE: To investigate the effect of pentoxifylline (PTX) in subjects with inactive Graves' ophthalmopathy (GO) through a specific quality of life (QOL) questionnaire and exophthalmometry readings. METHODS: Eighteen females were randomly divided in two groups. Group A (n=9) was treated with PTX 1200 mg orally/day for 6 months. Group B (n=9) received placebo during the initial 6 months and then PTX for another 6 months. Proptosis measurements were carried out every 3 months and a questionnaire graded from 0 to 10 according to the severity of the symptoms was performed at baseline and after placebo and PTX administration. RESULTS: At baseline, Group A questionnaire score values were 5.5 (median; range 3.5 to 8.0), and 5.0 after 6 months (3.0 to 6.0; p=0.01). In Group B, baseline values were not significantly different after 6 months of placebo: 6.0 (4.5 to 7.0) and 5.5 (4.5 to 7.0), respectively. However, a significant change was observed 6 months after PTX: 4.0 (2.0 to 5.0; p<0.001). Patients in Group A had a progressive improvement of proptosis during PTX: at baseline, 23 mm (median; range 20 to 32); after 3 months, 23 mm (18 to 30; p=0.02); and after 6 months, 23 mm (18 to 30; p=0.005). In Group B, proptosis remained stable during placebo: at baseline, 23 mm (21 to 25); after 3 months, 23 mm (20 to 25); and after 6 months, 23.5 mm (20 to 25). A significant change was observed after 3 and 6 months of PTX: 22 mm (19 to 24; p=0.0006) and 20.8 mm (17 to 25; p=0.0003), respectively. CONCLUSIONS: Pentoxifylline seems to improve the QOL of patients in the inactive phase of GO. The objective findings of the proptosis readings corroborate to suggest that PTX may be an effective and promising drug in the inactive phase of GO.

Assessment of cardiovascular risk in patients with erectile dysfunction: focus on the diabetic patient.

Erectile dysfunction (ED) is commonly associated with risk factors for cardiovascular disease, including diabetes. The prevalence of ED in diabetic patients is high--about 75% of diabetic men 60 yr of age or older had ED in one study. Endothelial dysfunction, accelerated atherosclerosis, and diabetic neuropathy likely contribute to ED in diabetics. As silent ischemia is common in the diabetic patient, and diabetes is now often thought of as a coronary heart disease risk equivalent, diabetic men seeking therapy for ED may be considered candidates for exercise stress testing. Phosphodiesterase 5 (PDE5) inhibitors improve erectile function in diabetic men with ED; however, efficacy rates may be somewhat lower than in nondiabetic men. Studies to date have suggested that PDE5 inhibitors per se do not cause an increase in myocardial infarction rates in men being treated for ED.

Management of erectile dysfunction: barriers faced by general practitioners.

AIM: To explore the barriers faced by general practitioners (GPs) in the management of patients with erectile dysfunction (ED). METHODS: This was a qualitative analysis of focus group discussions and in-depth interviews involving 28 Malaysian GPs. RESULTS: GPs' perception of ED being not a serious condition was a major determinant of their prescribing practice. Doctor's age (younger), gender (female), short consultation time and lack of experience were cited as barriers. The GPs' prescribing habits were heavily influenced by the feedback from the first few patients under treatment, the uncertainty of etiology of ED without proper assessment and the profit margin with bulk purchase. Other barriers include Patients' coexisting medical conditions, older age, lower socio-economic status, unrealistic expectations and inappropriate use of the anti-impotence drugs. Cardiovascular side effects and cost were two most important drug barriers. CONCLUSION: The factors influencing the management of ED among the general practitioners were multiple and complex. An adequate understanding of how these factors (doctors, patients and drugs) interact can assist in the formulation and implementation of strategies that encourage GPs to identify and manage ED patients.

Reasons for discontinuation of sildenafil citrate after successful restoration of erectile function.

AIM: To investigate the reasons for discontinuations of sildenafil after the successful restoration of erectile function. METHODS: One hundred fifty six patients, whose scores of erectile function domain of the 15-item International Index of Erectile Function (IIEF) increased to 26 or more after sildenafil medication, were included in this study. Six-months after the first sildenafil prescription, compliance to medication and the reason for discontinuity were reviewed by chart or surveyed by telephone. RESULTS: Fifty-four (34.6 %) of the 156 successfully treated patients discontinued sildenafil medication. The reasons for discontinuance were shortcomings in the partners' or patients' emotional readiness for the restoration of sexual life after long-term abstinence (37.0 %), fear of possible side effects (18.5 %), recovery of spontaneous erection (14.8 %), postponement of ED treatment because of co-morbid disease treatment (11.1 %), unwillingness to accept drug-dependent erection (7.4 %), high drug cost (3.7 %), unacceptability of planned sexual activity (3.7 %) and lack of sexual interest (3.7 %). CONCLUSION: The reasons for discontinuing sildenafil medication were primarily emotional or relationship-oriented, which indicates that simple recovery of a rigid erection is insufficient to restore sexual activity. More education about the effects of drug and the counseling of both partners is recommended to promote the successful recovery of sexual activity.

Cardiovascular assessment of ER-118585, a selective phosphodiesterase 5 inhibitor.

The aim of this study was to assess the cardiovascular effects of a selective phosphodiesterase 5 inhibitor ER-118585, 4-[(3-chloro-4-methoxybenzyl)amino]-1-(2-hydroxy-7-azaspiro[3.5]non-7-yl)-6-phthalazinecarbonitrile monohydrochloride. The present results indicated that 1) ER-118585 significantly inhibited the human ether-a-go-go related gene (HERG) tail current at 10 nM and above with an IC(50) value of 40.7 nM in human embryonic kidney 293 cells transfected with HERG cDNA; 2) ER-118585 at 100 and 1000 nM significantly increased the action potential duration (APD) at 50% and 90% repolarization in isolated papillary muscles of guinea pig; and 3) intravenous infusion of ER-118585 at 10 microg/kg/min significantly prolonged the QT interval by 10.5+/-1.6% from 281+/-2 ms to 311+/-6 ms in six anesthetized dogs subjected to atrial pacing. In consideration of both the plasma concentration of ER-118585 (984+/-78 nM, n=3) and its protein binding fraction (99.0+/-0.1%, n=5), the free plasma concentration was estimated at 9.8+/-0.8 nM, which is consistent with the minimum concentration of HERG current inhibition. In conclusion, these evaluation methods demonstrated that ER-118585 could prolong the QT interval via APD prolongation, attributable to the inhibition of the HERG potassium current.

Two pills, two paths: a tale of gender bias.

In Japan, it took over 30 years to register the contraceptive Pill, but it took only six months to approve Viagra. The Pill was developed in an academic institution and no large pharmaceutical manufacturer wished to market it. Viagra was developed inside a big company and actively promoted. In the USA, the Pill was almost removed from the market because of widely publicized reports of deaths, but mortalities associated with Viagra do not make the headlines. Viagra has been promoted by the famous, whilst those who use the Pill do not appear in advertisements. Even theologians have treated these two drugs according to different standards. It is suggested that this asymmetry is not accidental, but is an expression of a deep-seated dual standard that is ultimately driven by biosocial differences in male and female power, and reproductive agendas rooted in human evolution.

Cilostazol: a review of its use in intermittent claudication.

UNLABELLED: Cilostazol (Pletal) is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. It also exhibits antiproliferative effects on smooth muscle cells and has beneficial effects on high density lipoprotein-cholesterol and triglyceride levels.Randomized, double-blind, placebo-controlled 12- to 24-week trials in >2000 patients with moderate to severe intermittent claudication demonstrated that cilostazol generally significantly increased walking distances and improved quality of life compared with placebo. Additionally, a large comparative 24-week trial showed that cilostazol 100 mg twice daily was significantly more effective than pentoxifylline 400mg three times daily (pentoxifylline was not significantly different from placebo). Cilostazol was generally well tolerated. Adverse events reported significantly more often with cilostazol than with placebo included headache, diarrhea, abnormal stools, infection, rhinitis and peripheral edema and in comparison with pentoxifylline were headache, diarrhea, abnormal stools and palpitations. Adverse events were generally mild to moderate in intensity, transient or resolved after symptomatic treatment and rarely required treatment withdrawal. Significant drug interactions are observed when cilostazol is coadministered with other agents that inhibit cytochrome P450 (CYP) 3A4 (e.g. erythromycin or diltiazem) or CYP2C19 (e.g. omeprazole). As a result, in Europe cilostazol is contraindicated in patients receiving CYP3A4 or CYP2C19 inhibitors and in the US it is recommended that dosage reduction for cilostazol be considered during coadministration of cilostazol and CYP3A4 or CYP2C19 inhibitors. Conversely, cilostazol itself does not appear to inhibit CYP3A4. Coadministration of cilostazol with aspirin or warfarin did not result in any clinically significant changes to coagulation parameters, bleeding time or platelet aggregation. CONCLUSION: In six of eight well designed clinical trials, cilostazol was significantly more effective than placebo in increasing walking distances and improving the quality of life of patients with moderate to severe intermittent claudication. In addition, limited comparative data have shown that cilostazol has superior efficacy compared with pentoxifylline. Cilostazol is also generally well tolerated. Additional comparative trials are required to confirm these results, to determine the place of cilostazol in relation to other agents or exercise therapy and risk factor reduction alone, and to establish the effects of long-term treatment with cilostazol in patients with intermittent claudication. Cilostazol is contraindicated in several subpopulations of patients, particularly those with congestive heart failure and severe hepatic or renal impairment. Nonetheless, current data support the choice of cilostazol as a promising therapy amongst the limited options available for patients with intermittent claudication.

[Erectile disorders: the reality]. / Erectiestoornissen: de actuele situatie.

The grouping together of erectile dysfunction and erectile disorder (i.e. dysfunction with distress) has led to the presentation of incredibly high prevalences (up to 52%). When limited to erectile disorder, two Dutch open population studies, among men aged 40-79 years, show remarkably similar and more realistic prevalences, namely 3 to 10%. Although the 'Leiden Impotence Screening Test' appears to reliably exclude somatic aetiological factors, it would be preferable if the general physician posed such diagnostic questions. It is hoped that the availability of pharmacotherapeutic treatments (notably sildenafil) will not tempt the general physician to join the patient in his inclination to 'somatise' his erectile disorder. Both intracavernosal self-injection therapy and the implantation of an erectile prosthesis give rise to a large proportion of dissatisfied men. In the Netherlands to date, the number of continuation prescriptions for sildenafil equals the number of first prescriptions, which suggests that many men also stop with this therapy. In the Netherlands, health insurance companies only reimburse self-injections and prosthesis implantations. It can be argued that all cost-effective treatments for erectile disorder, including psychosexual therapy, should be reimbursed, or none at all.

A risk-benefit assessment of sildenafil in the treatment of erectile dysfunction.

Sildenafil is an oral treatment for erectile dysfunction (ED). It acts as an inhibitor of 3',5'-cyclic guanosine monophosphate-phosphodiesterase type 5. An effective treatment for ED is required to produce an erectile response sufficient for satisfactory sexual performance. This has been documented for sildenafil in men with ED of differing aetiologies and baseline severity in various types of clinical trials. Sildenafil treatment is characterised by a good tolerability profile and low treatment digcontinuation rate caused by treatment-related adverse effects. Most of the adverse effects associated with sildenafil are extensions of the pharmacological action of the drug. There is no significant difference in the adverse effect profile (headache, flushing, dyspepsia, nasal congestion and abnormal vision) of this agent as assessed by clinical data obtained either in the pre- and postlaunch periods. Because of its acceptable risk-benefit ratio, sildenafil can be prescribed to a very large group of patients with ED. The reports of serious cardiovascular events associated with the use of sildenafil (including anecdotal reports of deaths) have been very thoroughly analysed. A number of studies have not shown any difference in the risk of serious cardiovascular events in sildenafil- and placebo-treated patients. However, when making a risk-benefit evaluation, certain subgroups of patients need to be considered separately. In particular, sildenafil is contraindicated in patients receiving nitrate therapy. In some other subgroups of patients, the risks and benefits of treatment need to be assessed on an individual basis and it is hoped that additional data will clarify any possible risks associated with sildenafil administration such patients. It is helpful to compare the risk-benefit profile of sildenafil with the characteristics of other oral drugs for ED. According to the preliminary data, apomorphine and phentolamine are possible future options for the treatment of ED; however, there needs to be further clinical evaluation of these agents. Initial data have shown that sildenafil can be successfully combined with intracavernosal injection in patients nonresponders to either therapy. In conclusion, favourable characteristics make sildenafil suitable for the first-line therapy for a substantial proportion of patients with ED.