西地那非对充血性心力衰竭患者的运动、神经激素激动作用及勃起功能障碍的影响-对勃起功能障碍治疗的一项双盲、安慰剂对照、随机、前瞻性研究

勃起功能障碍(ED)在充血性心力衰竭(CHF)患者中是常见疾病。ED影响患者生活质量,进而会影响CHF治疗的依从性和有效性。所以,对合并CHF的ED患者不仅要治疗CHF,同时也应该有效治疗ED,并要注意治疗的安全性。西地那非是治疗ED的一线口服药,有效性和安全性已被广泛的临床应用所证实     

他达拉非治疗勃起功能障碍的安全性研究进展

勃起功能障碍(erectile dysfunction,ED)是中老年人的常见疾病。他达拉非自2002年10月开始用于治疗ED,其疗效确切,安全性高,因此越来越多的患者选择他达拉非来治疗ED。目前对他达拉非的作用机制、药代动力学、疗效、安全性等方面已经有了较多的基础及临床研究资料。本文就他达拉非治疗ED的安全性做一综述,以求该药物在临床上得到更安全的使用,为临床医生选择使用该类药物提供参考。     

西地那非治疗2型糖尿病患者勃起功能障碍有效且安全

勃起功能障碍（ED）是糖尿病常见的并发症，它使患者生活质量下降，丧失自尊，甚至影响性伴侣关系。西地那非是广泛应用于治疗ED的选择性PDE5抑制剂，其对2型糖尿病患者ED的疗效和安全性如何呢？     

西地那非治疗勃起功能障碍的临床进展

自1998年全球上市以来,西地那非治疗勃起功能障碍(erectiledysfunction,ED)积累了2千3百万患者的的临床应用经验,证明是有效的和安全的。本文对西地那非的作用机制、代谢过程进行回顾,对西地那非用于ED诊断、连续服用可治愈ED、规范性治疗、联合用药治疗ED、合并其他疾病时的治疗用药、循序渐进的ED治疗方案以及对视力影响的安全性等问题进行综述。     

西地那非在心血管疾病患者应用的安全性研究进展

西地那非被广泛应用于治疗阴茎勃起功能障碍 (ED),由于许多ED患者同时患有心血管疾病,这类疾病患者应用西地那非治疗的安全性一直是广大医生和患者关注的问题,本文回顾分析西地那非在心血管患者应用的安全性方面的数据资料,就西地那非在心血管疾病患者应用的安全性方面的研究进展进行了综述。     

西地那非在中国男科临床应用十年回顾

自从10年前西地那非进入中国男科临床以来,其在治疗ED方面的疗效和安全性已被证明,并为国内医生和患者所接受,对各种病因、不同程度、不同年龄的ED患者均具有良好疗效。近年来,西地那非不仅广泛应用于ED治疗上,国内相关研究还显示西地那非在治疗或联合治疗男性早泄等方面也具有一定的疗效,本文在此做一综述。     

肾移植病人的勃起功能障碍：西地那非的有效性

肾功能衰竭是引起勃起功能障碍（ED）的一个重要原因，随着医疗技术的发展，越来越多的肾功能衰患者能够接受肾移植手术治疗。 那么肾移植对已经存在ED的患者有何影响？肾移植后有多少患者会新发ED？而目前治疗ED的一线口服药西地那非对肾移植术后患者的勃起功能障碍的疗效和安全性又如何呢？Russo D等人对此进行了相关研究，他们首先对肾移植病人采用国际勃起功能指数（IIEF）评价其勃起功能。     

西地那非枸橼酸盐对稳定型心脏病合并勃起功能障碍患者的有效性和安全性研究

心血管疾病和勃起功能障碍(ED)有着诸多共同危险因素,所以心脏病患者合并ED者比较常见,而对于这类人群ED的治疗,既要考虑疗效又要注意安全性。DeBusk RF等人进行了一项双盲、安慰剂对照研究,很好地评价了枸橼酸西地那非治疗合并稳定型心脏病(CAD)的ED患者的有效性和安全性[AmJ     

西地那非对服用抗高血压药物所致勃起功能障碍的效果:西地那非研究组

在男性高血压患者中,勃起功能障碍(ED)有着较高的发病率。这些患者一般都要长期服用抗高血压药物。而对于ED的治疗理应考虑药物相互作用所带来的疗效和安全性问题。西地那非是治疗ED的一线口服药,而该药在此类患者中的疗效如何,安全性会不会受到影响呢?Kloner RA等人进行的一项     

脂肪源性干细胞治疗阴茎勃起功能障碍的研究进展

脂肪源性干细胞(ADSCs)是从脂肪组织中分离得到的一种多能干细胞,具有自我更新和多向分化潜能,可向神经细胞、平滑肌细胞及内皮细胞等多种细胞类型分化。而勃起功能障碍(ED)是一种常见的男性性功能障碍疾病,对患者及其伴侣的生活造成了很大的负面影响。目前治疗ED的方法有手术及药物等,其中5-磷酸二酯酶抑制剂作为临床治疗ED的一线用药,仍对少部分患者不敏感,而且存在无法改善或者治愈ED的病理基础。迄今为止的动物试验及临床前期研究已经证实了ADSCs治疗ED的安全性及有效性,其可通过旁分泌作用达到治疗ED的作用。本文就近5年来ADSCs治疗ED的研究进展进行综述。     

Characterising the benefit of apomorphine SL (Uprima) as an optimised treatment for representative populations with erectile dysfunction

The clinical profile for apomorphine sublingual (SL), a new centrally active agent for the management of the erectile dysfunction (ED) patient, is described in this article. Apomorphine SL is shown to be rapid in onset (71% of patients within 20 min) with a consistent, predictable response that is independent of severity (mild, moderate or severe), the underlying aetiology or the presence of significant co-morbidities (coronary artery disease, hypertension, etc). Importantly, there is also consistent long-term clinical benefit (>90% of attempts being successful over 18 months), for patients who respond to therapy and a benign side effect profile (<13.4% patients with adverse events). This formulation of apomorphine has a speed of onset and overall clinical profile that may offer particular advantages to the patient in terms of spontaneity and predictability of response. ED is a complex disease of varying aetiologies and severities often associated with a number of co-morbidities that require diverse solutions. Given the need for customisation of therapy to individual patient needs, the clinical profile of apomorphine SL would indicate that it will make a most welcome addition to the physician's armamentarium against ED.     

Apomorphine: an update of clinical trial results

Apomorphine SL (TAP Holdings, Deerfield, IL) is a centrally acting treatment for erectile dysfunction (ED) that has been undergoing phase III trials. Over 3000 men have received apomorphine SL and over 75,000 doses have been taken. In the first three phase III parallel arm cross-over double-blind studies 854 patients were given a total of 8263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 y old and outcome measures included per attempt rates of intercourse and erections firm enough for intercourse as well as psychometric instruments and partner responses. The majority (74.1%) had moderate and severe grades of ED on admission to the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia and 16% had diabetes. Erections occurred rapidly (10-25 min) and in 54.4% of attempts at 4 mg (vs 33.8% placebo). A majority of the attempts at intercourse (50.6%) were successful at 4 mg in patients when recorded on a per-attempt basis. The most common but infrequent and mild side effect of nausea decreases with use. The phase III trials of apomorphine SL show that there is a clinically important restoration of erectile function from this new formulation of apomorphine. It has a rapid and safe effect through action in the central nervous system. Apomorphine SL brings a new choice to the management of ED that will further benefit the millions of couples affected. International Journal of Impotence Research (2000) 12, Suppl 4, S67-S73.     

Effects of apomorphine and L-dopa on the parkinsonian bladder

Neurogenic bladder frequently occurs in Parkinson's disease. Detrusor hyperreflexia is a consequence of nigrostriatal dopamine depletion, whereas the cause of hyporeflexia remains unclear. We compared the results of cystometry and urethral profilometry with and without apomorphine (and L dopa) in 12 idiopathic parkinsonians with urinary disorders free of dopaminergic treatment. Whereas hyperreflexic patients improved with apomorphine, and to a lesser extent with L dopa, these drugs had no effect on hyporeflexic patients. These results confirm the role of dopaminergic lesions in the occurrence of bladder hyperreflexia and the possible implication of nondopaminergic lesions in the occurrence of hyporeflexia.     

Tramadol inhibits rat detrusor overactivity caused by dopamine receptor stimulation

PURPOSE: In patients with Parkinson's disease an imbalance between stimulatory D2-like receptors and inhibitory D1-like receptors may contribute to detrusor overactivity. Apomorphine, which stimulates D1-like and D2-like dopamine receptors, induces detrusor overactivity in rats. Tramadol is an analgesic drug that stimulates opioid receptors and inhibits reuptake of serotonin and noradrenaline. To evaluate a potentially inhibitory effect of tramadol the drug was given to rats with apomorphine induced detrusor overactivity. MATERIAL AND METHODS: Female Sprague-Dawley rats were used. During anesthesia catheters were introduced into the bladder dome, femoral vein and subcutaneously (SC). Three days later the rats were placed in a metabolism cage and voiding was stimulated by infusing saline into the bladder. Micturition parameters were recorded and compared after the administration of apomorphine and tramadol or vehicle. Desmopressin was given as pretreatment to suppress the diuresis produced by tramadol. RESULTS: While 30 microg kg-1 apomorphine SC was devoid of effect, 60 and 100 microg kg-1 apomorphine SC induced a transient detrusor overactivity. Tramadol (1 mg kg-1) was without effect but 5 and 10 mg kg-1 tramadol intravenously attenuated the effects of apomorphine, while inducing prominent diuresis. Pretreatment with desmopressin, which did not alter cystometry or the effects of apomorphine, abolished diuresis. In these rats 5 and 10 mg kg-1 tramadol intravenously abolished the overactivity caused by apomorphine SC. CONCLUSIONS: Tramadol effectively suppresses apomorphine induced detrusor overactivity in doses shown to have analgesic activity. Hence, tramadol may provide an approach to treat lower urinary tract disorders in which dopamine receptor activation is involved.     

Alfuzosin improves penile erection triggered by apomorphine in spontaneous hypertensive rats

OBJECTIVES: Growing evidence suggest that BPH is a risk factor for ED. Since alfuzosin is a cornerstone in the treatment of BPH patients, we assessed the effect of alfuzosin on erectile function in rats when combined with a pro-erectile drug such as apomorphine. METHODS: Potencies of alfuzosin, apomorphine or the combination to relax norepinephrine (NE) precontracted corpus cavernosum tissue of spontaneous hypertensive rats (SHR) were determined. In anaesthetized rats, intracavernous and blood pressures were recorded after administration of apomorphine (10-250microg/kg s.c.) and alfuzosin (3-30microg/kg i.v.). RESULTS: Alfuzosin fully relaxed the NE-precontracted penile tissue (pIC(50)=6.62+/-0.7) while apomorphine, up to 10microM, did not produce any relaxation. The potency of alfuzosin to relax erectile tissue was not further enhanced with 10microM apomorphine. Apomorphine induced erections in rat while alfuzosin alone did not. However, alfuzosin (30microg/kg) significantly enhanced the potency of apomorphine, to induce erections (ED(50)=25microg/kg versus 57microg/kg). In addition, alfuzosin even at 3microg/kg, significantly increased the intracavernous pressure (ICP) during erectile events up to 52-55mmHg when compared to ICP values of 29mmHg with 50microg/kg apomorphine alone. CONCLUSION: These results show that alfuzosin enhances the number and amplitude of erections induced by apomorphine in SHR. Therefore, clinical evaluation of alfuzosin in association with apomorphine is warranted.     

A comparative, crossover study of the efficacy and safety of sildenafil and apomorphine in men with evidence of arteriogenic erectile dysfunction

The aim of the study was to establish and compare the efficacy and safety of sildenafil and apomorphine in men with arteriogenic erectile dysfunction (ED). In all, 43 men with ED and postinjection max penile systolic velocity <25 cm/s in repeated Doppler ultrasonography were included. Of these, 24 men started on apomorphine 2 mg and 19 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg according to effectiveness and tolerability. Safety was evaluated according to adverse events (AEs) and patient withdrawal. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on event log data. The incidence of AEs with apomorphine 3 mg was higher than with sildenafil 100 mg. Two men on apomorphine 3 mg discontinued treatment due to AEs. The overall success rate of sildenafil was 63.7% compared to 32.1% of apomorphine (Pearson chi(2), P<0.01). Of all men, 25 (58.1%) responded to sildenafil 50 mg without the need for dose increase, while only one responded to apomorphine 2 mg. The response to sildenafil 50 mg was age related (analysis of variance, p=0.04). Satisfaction was reported by 76.75 and 13.95% of patients for sildenafil and apomorphine, respectively, but 20.9% were not satisfied with any of the two drugs. In conclusion, this study provides clear evidence that sildenafil, even at 50 mg dose, is more effective than apomorphine 3 mg in men with arteriogenic ED. The fact that one out of five patients is not satisfied with the above-studied drugs shows that new oral agents need to be evaluated for the treatment of this disorder.     

Efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction. A comparative crossover study

To compare the efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction (ED), 40 men were studied. Post-injection penile peak systolic velocity was greater than 25 cm s(-1). Twenty men started on apomorphine 2 mg and 20 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg, respectively, if necessary. After a 1-week washout period each group switched to the other treatment mode. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on an event log data. The majority (85%) of the men had concomitant diseases, risk factors for ED and 95% were heavy smokers. The overall success rate of apomorphine was 62.7%, compared with 73.1% of sildenafil (Yates-corrected chi-square, P < 0.0004). The response to apomorphine 2 mg and sildenafil 50 mg was age related. Sildenafil was statistically more effective than apomorphine in impotent men with normal penile Doppler. Given the contraindication of sildenafil in men taking nitrates and the quick time of action of apomorphine, the two drugs are satisfactory first line therapeutic tools in such individuals and the choice should be based on patient's needs and preferences.     

Safety and Tolerability of Apomorphine SL in Men with Cardiovascular Disorders

Objective: Since many men with erectile dysfunction (ED) also have cardiovascular (CV) disease and are likely to be taking antihypertensive medications, nitrates, or other medications, the risk of side effects of oral drug therapy for ED in the presence of these conditions was evaluated.Methods: Clinical trials involving apomorphine SL for ED were evaluated to determine the safety and tolerability profile in men with coronary artery disease, hypertension, hyperlipidemia, and diabetes mellitus in comparison to other oral agents.Results: None of the subpopulations of men, whether analyzed by specific CV disease, presence of diabetes, or any concomitant medication were at increased risk for side effects and adverse events associated with apomorphine SL treatment. In particular, there were no substantive changes in the adverse event rates in those patients concurrently receiving antihypertensive medications nor in those men treated with short- or long-acting nitrates.Conclusions: Apomorphine SL is well tolerated and safe in men with ED associated with concomitant CV disorders or risk factors. Furthermore, apomorphine SL is not contraindicated in men with stable coronary artery disease who take nitrate medication and is well tolerated and safe in men concurrently receiving CV medications including nitrates and various classes of antihypertensives.     

A European multicentre study to evaluate the tolerability of apomorphine sublingual administered in a forced dose-escalation regimen in patients with erectile dysfunction

OBJECTIVE: To determine the risk-benefit ratio of a forced dose-escalation regimen (2 to 3 to 4 mg) in a European clinical study evaluating apomorphine sublingual (SL) in treating erectile dysfunction (ED), by evaluating the overall tolerability and efficacy of the regimen compared with placebo in patients with ED, and evaluating efficacy by assessing the proportion of successful attempts resulting in sexual intercourse. PATIENTS AND METHODS: This randomized, double-blind, two-arm, parallel-group study was conducted in 507 patients enrolled at 34 European sites. After a 1-2 week screening period, patients were treated for 8 weeks with either placebo or apomorphine SL administered as a forced dose-escalation regimen. Heterosexual men (aged 18-70 years) were eligible for participation in the study if they were in stable health, a stable relationship of > or = 6 months duration, had a history of erectile inability, and were diagnosed with ED (successful in fewer than half of attempts to attain and maintain an erection firm enough for intercourse during the 30 days before screening). Patients provided information (recorded on diary cards and reviewed at each study visit) about the frequency and success in achieving erections and of sexual intercourse attempts during both the screening and treatment periods. The dosing regimen required patients to take one tablet of apomorphine SL (2 mg for 2 weeks, then 3 mg for 2 weeks and finally 4 mg for the remaining 4 weeks) or placebo 15-25 min before intercourse, and intercourse was to be attempted at least twice a week. Safety data were collected throughout the 8-week study period, and included recording adverse events, vital signs and changes in laboratory test values for standard haematology and biochemistry variables. The primary efficacy variable was the proportion of successful attempts, defined as an erection rigid enough for sexual intercourse, occurring after dosing (successful intercourse rate). The proportion of erections achieved was a secondary efficacy variable. RESULTS: Of the 507 patients, 254 received apomorphine SL and 253 received placebo; 87% of patients in both groups completed the 8-week treatment period. Of the patients receiving apomorphine SL, 24% had hypertension, 11% had coronary artery disease, 10% had diabetes, and 5.5% had benign prostatic hypertrophy; 62.6% of treated patients received concomitant medications for these maladies. The treatment groups were balanced for demographic and baseline variables, including comorbidity factors. Treatment-emergent adverse events, reported by > 5% of patients in the treated group, were nausea (9.8%), dizziness (7.1%) and headache (6.7%), compared with 0.4%, 2.4% and 4.0%, respectively, in the placebo group. Sixty-six patients withdrew from the study, 16 because of study drug-related adverse events (12 from the apomorphine and four from the placebo group). Six patients (three in each group) reported a total of nine serious treatment-emergent adverse events, all of which resolved by the end of the study. In the intention-to-treat population, the proportion of successful attempts at sexual intercourse and of erections were statistically greater in the apomorphine than in the placebo group (P = 0.001 and 0.021, respectively); analysis of the per-protocol population results confirmed this significant difference. CONCLUSION: This European study supports the safety and tolerability of apomorphine SL despite the forced escalation to a 4-mg dose (exceeding the approved 2-3 mg dose). Adverse effects were not treatment-limiting. These results further support the clinically significant efficacy of apomorphine SL for treating ED at all doses used. The risk/benefit ratio supports apomorphine SL as a safe and effective alternative in managing ED.