西地那非对离体大鼠大动脉环NO/cGMP依赖性舒张作用和动脉环血管舒张作用

西地那非是一种高选择性PDE5抑制剂,用以有效治疗ED。为了研究西地那非对老鼠大动脉环NO/cGMP依赖性舒张作用和动脉环血管舒张作用。Sharabi,FM等人进行了一项研究,浓度≥1×10(-8)M时西地那非显著     

西地那非长期治疗可改善高脂肪喂养小鼠的能量平衡和胰岛素活动

一氧化氮(NO)-环磷酸鸟苷(cGMP)信号的刺激可导致血管舒张和肌肉葡萄糖摄入(MGU)增加。Ayala JE等人进行了一项研究,观察长期应用磷酸二酯酶-5(PDE_5)抑制剂西地那非通过抑制环磷酸鸟苷水解,是否可以改善由高脂饮食所致胰岛素抵抗大鼠的能量平衡和体内胰岛素活性。对高脂肪喂养大鼠采用西地那非联合L-精氨酸或单用西地那非治疗12周,通过增加能量消耗引起体重下降和减少脂肪堆积。然而在西地那非治疗组中的小鼠体内UCP-1(解偶联蛋白-1)水平并未增加。长期采用西地那非联合L-精氨酸或单     

西地那非通过蛋白激酶G／MAPK通路诱导血管形成

人们对血管形成过程中的cGMP降解通路缺乏关注,为此Pyriochou A等人进行了一项研究,观察cGMP特异性的磷酸二酯酶(PDE_5)抑制剂是否对新生血管的生长有影响。在体内将鸡胚绒毛尿囊膜(CAMs)与西地那非共同孵育可增加血管的长度,而且这一作用具有剂量依赖性。同时,将培养的内皮细胞(ECs)与PDE_5抑制剂共同孵育可促进ECs的增殖、迁移,及形成管样结构。如果用可溶性鸟苷酸环化酶(sGC)抑制剂ODQ或蛋白激酶G(PKG)Ⅰ抑制剂DT-3进行预处理,则西地那非促进EC形成新生血管的作用将     

口服西地那非不损害移植肾脏的功能

勃起功能障碍(ED)是男性肾脏移植受者的一个重要问题,西地那非作为治疗ED的一线口服药,应用于这类ED患者是否安全?Malavaud B的研究提供了肯定的答案。西地那非(万艾可)通过维持3′,5′环磷酸鸟苷(cGMP)介导海绵体平滑肌松弛而改善勃起。它亦可引起全身性血管舒张,使血压轻微降低。研究评估的是单个剂量的西地那非对伴有ED的肾脏移植受者的移植物功     

西地那非可预防肺动脉高压患儿停用NO后症状反弹

肺动脉高压患者停用NO后常常有症状反弹现象,反弹表现为肺动脉(PA)压升高,心肺功能不稳定,有些患者预期治疗结束后仍需继续应用NO,使人们对NO的疗效产生疑问。复发原因部分与体内原有的cGMP瞬时耗竭有关。5-型磷酸二酯酶抑制剂西地那非,有可能通过提高体内cGMP水平预防这种现象发生。为此Namachivayam P等人进行了一项相关研究,研究西地那非对撤除NO治疗后症状反弹的预防作用(反弹是指肺     

肿瘤细胞和心肺血管中cGMP特异性PDE5及其抑制剂的新作用

Zhu B等人进行了一项研究,分析了肿瘤细胞和心肺血管中cGMP(特异性的PDE5和其他抑制剂)的异常功能.目前已知在正常的生理过程(如平滑肌收缩和舒张)中PDE5是调节CGMP特异信号传导途径的中一个关键酶.因此,酶的抑制剂能够通过降低cGMP组织浓度来改变病生理过程,因此西地那非、他达拉非和伐他那非已经成功地用于治疗勃起功能障碍.     

阴蒂海绵体中磷酸二酯酶5表达及淫羊藿甙对cGMP浓度的影响

目的　探讨阴蒂海绵体中磷酸二酯酶 5表达及淫羊藿甙对cGMP浓度的影响。　方法　通过反转录聚合酶链反应技术 (RT PCR)检测兔阴蒂海绵体中PDE5mRNA的表达 ;12 5I放射免疫法测定不同浓度淫羊藿甙对阴蒂海绵体内PDE5酶底物cGMP浓度的影响 ,西地那非作为阳性对照 ,分别计算EC50 。　结果　阴蒂海绵体组织中有PDE5的表达 ,淫羊藿甙可明显提高阴蒂海绵体内的cGMP浓度 ,具有显著的浓度依赖性。　结论　淫羊藿甙对阴蒂海绵体平滑肌细胞内cGMP水平的影响可能是通过PDE5发挥作用 ,与NO cGMP信号通路有关。     

西地那非能提高慢性心衰患者血流介导的血管舒张反应

心衰患者内皮细胞依赖的、血流介导的血管舒张反应功能受损,部分是由于血管平滑肌上介导血管舒张因子机制的cGMP低反应性所导致的。但使用5型磷酸二酯酶(PDEs)抑制剂,西地那非,阻断cGMP的降解是否能影响心衰患者血流介导的血管舒张还是未知的。为此,Katz SD等进行了一项随机、双盲试验。入选慢性心衰患者48名,随机一次     

西地那非治疗勃起功能障碍时间效应窗

西地那非治疗勃起功能障碍(erectiledysfunction,ED)的疗效与该药的药代动力学以及选择性行为时间密切相关。西地那非治疗ED作用的时间效应窗,包括服用西地那非治疗ED达到成功性交所需勃起硬度的最短时间、达到最佳勃起状态的时间、以及长期服用的有效性等问题随着研究的深入进一步阐明。本文对此进行综述。     

肺动脉高压治疗的新手段:5型磷酸二酯酶抑制剂

Ghofrani等进行了一项研究，分析了5型磷酸二酯酶抑制剂（PDE5I）对于治疗肺动脉高压（PHT）当中的应用。由于西地那非（一种5型磷酸二酯酶抑制剂）作用于NO／cGMP信号传导通路，所以它可选择性降低PHT患者肺循环阻力、改善其症状和提高其运动耐量。SUPER-1 Ⅲ期临床研究已经明确证实西地那非应用于PHT的安全性和有效性，从而西地那非在PHT方面的临床应用得到了证据支持。近来，几大专业协会的指南已经包含西地那非用于PHT的治疗，并且得到了高级别循证医学证据支持。西地那非还能与其他药物联合治疗PHT和其他形式的肺源性高血压。     

西地那非联合小剂量他达拉非治疗重度勃起功能障碍的临床观察

目的探讨重度勃起功能障碍更简单易行的治疗方法。方法本文选择汉中市人民医院泌尿外科2016年10月至2019年2月门诊收治的重勃起功能障碍的65例患者。随机分为联合用药组(n=33)和单一用药组(n=32)。单一用药组使用西地那非片100mg,按需口服治疗;联合用药组在单一用药组的基础上,联合口服他达拉非5mg,每天1次。观察比较两组患者的疗效及不良反应发生情况。选用男科国际常用的疗效评估方法:勃起功能国际问卷(IIEF-5)评分、勃起硬度(EHS)评分,来评估疗效。结果联合用药组效果明显优于单一用药组,两组差异有显著统计学意义(P<0.05)。结论西地那非和他达那非联合使用治疗重度勃起功能障碍,较单用西地那非临床疗效显著,并不显著增加副作用。可以有效改善患者生活质量,值得推广应用。     

万艾可治疗ED时对BPH引起LUTS改善的研究

目的 :探索、研究万艾可在治疗阴茎勃起功能障碍 (ED)时对由良性前列腺增生 (BPH)引起的下尿路症状(LUTS)的影响。　方法 :32例ED同时伴有BPH的研究对象 ,采用IIEF 5问卷表和IPSS评分表 ,在服用万艾可前和服药后 6个月分别各填写一次 ,应用单因素方差分析对所得到的前后评分进行统计学分析。结果 :在服药前32例ED中 ,轻、中、重分别为 14、13、5例 ,BPH中轻、中、重分别为 3、15、14例 ;服药后IIEF 5评分平均上升4 2 .36 % ,IPSS评分平均下降 2 0 .14 % ,两者在统计学上都有显著性差异 ,P <0 .0 1。　结论 :在治疗中老年性ED合并BPH中 ,应用万艾可既能治疗ED ,取得完美的性生活 ,又能达到改善由BPH引起的LUTS。万艾可是一治疗ED有效的药物 ,但对于前列腺基质平滑肌亦有辅助性松弛作用 ,因此也有助于BPH时LUTS的缓解。     

Phosphodiesterase inhibitors in the treatment of erectile dysfunction in spinal cord-injured men

STUDY DESIGN: Open, before-after study. OBJECTIVE: To assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) in spinal cord-injured (SCI) patients. SETTING: Home- and clinic-based assessments in the outpatient department at the Centre Bouffard Vercelli, Cerbère France. METHODS: Clinic trials with Sildenafil (Viagra) on 120 patients, Tadalafil (Cialis) on 54 patients and Vardenafil (Levitra) on 66 patients were performed. Flexible doses of PDE5 inhibitors were given depending on efficacy and tolerability, from 50 to 100 mg for Sildenafil, and from 10 to 20 mg for Vardenafil and Tadalafil. Each trial was performed after a week's interval. The efficacy was self-assessed by the patients on a six-point quantitative scale assessment. The response to treatment was assessed at home in 90 patients (57 patients on Sildenafil, 12 patients on Vardenafil and 21 patients on Tadalafil) using the International Index of Erectile Function (IIEF). RESULTS: In clinic trials, PDE5 inhibitors were effective (rigidity enough for penetration) in 85% of the patients on Sildenafil, 74% of the patients on Vardenafil and 72% of the patients on Tadalafil. The mean duration of erection was 34, 28 and 26 min, respectively. Adverse effects were mild, usually attenuated with continued dosing. More than 70% of the patients on Vardenafil and Tadalafil required higher doses of 20 mg, whereas 50 mg of Sildenafil was effective in 55% of the patients. Two-thirds of our patients on Tadalafil reported a duration of action longer than 24 h. The presence of an upper motor neuron lesion was significantly associated with therapeutic success, lower motor neuron lesions and cauda equina patients were poor responders. Other variables such as completeness of lesion had no impact. In the follow-up visits, the IIEF global scores and three IIEF domains (erectile function, intercourse satisfaction and overall satisfaction) were significantly improved in all patients. Patients on Sildenafil showed a significant improvement of orgasmic function, ejaculation (Question 9) and orgasm (Question 10). CONCLUSION: Sildenafil, Vardenafil and Tadalafil are all effective and well-tolerated treatments for ED in SCI patients. Although no statistical analysis could be applied on these data, these results might indicate that Sildenafil is more effective in treating ED. Clinic trials are important for proper dose titration and appropriate education of the patients.     

Efficacy and safety of fixed-dose oral sildenafil in the treatment of sexual dysfunction in depressed patients with idiopathic Parkinson's disease

OBJECTIVE AND METHODS: The efficacy and safety of oral Sildenafil, a potent inhibitor of phosphodiesterase type 5, were evaluated in depressed men with idiopathic Parkinson's disease and erectile dysfunction. Thirty-three men were enrolled in a 4-month prospective, open-label, fixed-dose study, and received 50mg of Sildenafil in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of IIEF, a global efficacy question, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale-21 (HDRS-21). RESULTS: At the end of the study, improved erections were reported by 84.8% of patients. Sildenafil significantly increased patients' ability to achieve and maintain erections. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction and overall sexual satisfaction. BDI and HDRS scores improved from baseline to the end of the study. A clear improvement of depressive symptoms was observed in 75% of patients. Sildenafil was well tolerated in all the patients. CONCLUSIONS: Treatment with oral Sildenafil improves erectile function and, indirectly, depressive symptoms in patients with idiopathic Parkinson's disease stages 1-3, and is well tolerated.     

Use of sildenafil in penile implant patients

OBJECTIVE: To determine whether Sildenafil use in the patients with penile implants provided additional sexual satisfaction. MATERIAL and METHODS: 12 patients who had had insertion of inflatable penile implants were given oral Sildenafil in the period following implantation. They were assessed for sexual satisfaction before and after oral Sildenafil use. The assessment was done using questions 7, 8, 13 and 14 of the International Index of Erectile Function (IIEF) questionnaire. These four questions of the IIEF questionnaire address the domain of satisfaction in male sexual behavior. Each person answered these questions using a scale of 1 (almost never or never) to 5 (almost always or always). The main answer to each question after Sildenafil was compared to the mean answer before. RESULTS: There was a significant increase in the mean answer score to each of these questions. CONCLUSION: Supplemental Sildenafil can increase the sexual satisfaction of patients with inflatable penile implants.     

Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time

Sildenafil is one of two oral drugs approved for first-line treatment of erectile dysfunction (ED). Anecdotally, some young healthy men who wish to enhance their sexual performance are requesting or abusing sildenafil. In this randomized double-blind, placebo-controlled clinical study, we investigated the effect of sildenafil in young men without ED. A total of 60 young healthy men age 20-40 y with no reported ED were enrolled for this single-dose home-use study. Subjects had used no medication in the 6 months prior to the study. All had been engaged in a stable relationship for at least 3 months. After completing the IIEF-5 questionnaire, patients were randomized in a double-blind fashion to receive either one 25 mg tablet of sildenafil (group 1) taken prior to intercourse, or an identical placebo tablet (group 2). All subjects completed a questionnaire relating to their erectile quality. There were no differences between the two groups in the reported improvement of erection quality, 12/30 sildenafil vs 10/30 placebo (Fisher's test, P=0.79). Sildenafil caused a significant reduction of the postejaculatory refractory time (12/30 vs 4/30) (chi(2) test, P=0.04). Sildenafil does not improve erections in young healthy men. Sildenafil should not be given to young healthy men to improve their erections and patients should be advised against recreational abuse of the drug. In this limited single-dose home study, sildenafil appears to reduce the postorgasmic refractory time. Although controlled studies are needed to evaluate the efficacy of erection-enhancing drugs in premature ejaculation, it is possible that sildenafil might be useful for this indication.     

Oral sildenafil citrate as an effective alternate in the treatment of postoperative pulmonary hypertensive crisis after congenital heart surgery

A five-month-old girl of Down syndrome underwent a corrective surgery for complete atrioventricular septal defect. Her postoperative course was complicated with pulmonary hypertensive (PH) crises despite nitroglycerin (NTG) infusion and inhaled nitric oxide (NO). Sildenafil citrate, a phosphodiesterase 5 inhibitor, was administered through a nasogastric tube at a starting dose of 0.3 mg/kg by stepwise increment to the maximum dose of 2 mg/kg 4 hourly. Sildenafil citrate dramatically lowered pulmonary arterial pressure and the patient was weaned from NTG and NO without PH crisis. There was no side effect after sildenafil citrate administration. Oral sildenafil citrate is a safe and potent adjunct to the existing therapies for postoperative PH in infants after open heart surgery.     

Sildenafil in the treatment of erectile dysfunction in men with diabetes: demand, efficacy and patient satisfaction

The objective of this study is to describe the eligibility, consumption, efficacy and patient satisfaction when treating men with diabetes with Sildenafil. The study is a prospective, self-reported, flexible-dose study. In total, 45 patients with diabetes (type 1 or 2), complaining of erectile dysfunction, were treated with Sildenafil over a 12-week period. Efficacy was assessed using a patientlog, a general satisfaction questionnaire and the International Index of Erectile Function (IIEF). Of 326 men, 192 reported erectile dysfunction, 79 did not fulfil the criteria for Sildenafil treatment and 49 declined to participate. In the group of 33 (age 45-75 y, mean+/-s.d.: 58.1+/-7.2) completing the study, erectile function was significantly improved (P < 0.0001). A total of 12 patients (36.4%) experienced no treatment effect at all. Eligibility and desire for treatment was low. Sildenafil is far from being a 'cure all' in the treatment of ED in diabetes.     

Sildenafil augments pelvic nerve-mediated female genital sexual arousal in the anesthetized rabbit

The NO-cGMP pathway has been implicated in clitoral and vaginal smooth muscle relaxation based on previous immunochemical, biochemical and physiologic studies. There are limited data from in vivo studies demonstrating enhancement of the genital sexual arousal response by pharmacologic agents influencing the NO-cGMP pathway. The goal of this study was to investigate if sildenafil, a phosphodiesterase type-5 inhibitor, facilitated female genital sexual arousal in an animal model in response to pelvic nerve stimulation (PNS). Using female New Zealand White rabbits, we measured the following parameters before, during and after PNS at 4, 16, and 32 Hz: a) hemoglobin concentration and oxygen saturation in female genital (vaginal, labial, clitoral) tissues by laser oximetry; b) clitoral blood flow by laser Doppler flowmetry; c) vaginal luminal pressure by a balloon catheter pressure transducer; d) vaginal lubrication by tampon. Sildenafil was administered intravenously (0.21 microg/kg, 0.42 microg/kg, 2.1 microg/kg) to achieve a systemic concentration of 5, 10 and 50 nM, respectively. After 20 minutes, physiologic measurements were repeated. Sildenafil (50 nM) caused a significant increase in genital oxyhemoglobin concentration and a significant decrease in genital deoxyhemoglobin concentration. Sildenafil also increased the duration of response following PNS, relative to genital hemoglobin concentration and mean clitoral blood flow. Sildenafil caused a decrease in vaginal luminal pressure and resulted in an increase in vaginal lubrication. These data indicate that the NO-cGMP pathway is involved in the physiologic mechanism of female genital arousal and that sildenafil facilitates this response in an in vivo animal model.