治疗勃起功能障碍的新药伐地那非

继西地那非 (伟哥 )之后 ,美国FDA批准了第 2种治疗勃起功能障碍的伐地那非 (vardenafil,商品名Levitra) ,与西地那非相比 ,其作用开始更为迅速。单项口服本品后 ,仅可吸收 15 % ,服后 1/2～ 1h可达血药峰值。与西地那非相同 ,达峰中值时间为 1h。如使用较高剂量 (2 0mg ,4 0mg)则较低剂量 (10mg)提前达峰。中等脂肪餐不会改变本品的药动学 ,但高脂肪餐则可使Cmax下降 18% ,并延迟达峰时间 1h。 >6 5岁男性的血药浓度较高。本品在肝内通过P4 5 0CYP3A4代谢 ,大部分随粪便排泄 ,其消除t1/2 为 4～ 5h。本品如与P4 5 0CYP3A4强抑制剂合…     

勃起功能障碍治疗药物市场走势

自1998年3月Pfizer公司的西地那非(sildenafil，Viagra)在美国首次上市以来，勃起功能障碍治疗药物市场发生了巨大变革，此蓝色菱形小丸很快风靡世界，其2002年的全球销售额高达17．35亿美元。而2003年Lilly ICOS及GlaxoSmith-Kline-Bayer两公司在欧美相继分别推出同效药物他达拉非(tadalafil，Cialis)和伐地那非(vadenafil，Levitra)，这又会导致西地那非及勃起功能障碍治疗药物市场发生什么变化呢?     

勃起功能障碍治疗药Vardenafil

50岁以上的糖尿病男性病人中约有50%～60%患勃起功能障碍,由糖尿病所致神经和血管损伤而造成的勃起功能障碍尤为难治.Bayer公司研制的强效选择性磷酸二酯酶5(PDE5)抑制剂Varde-nafil(Bay-38-9456)则有可能给那些糖尿病所致勃起功能障碍病人带来福音(其结构见本期338页).     

伐地那非与勃起功能障碍

勃起功能障碍(ED)是指持续3个月以上阴茎不能勃起和(或)不能维持勃起状态。ED是一种与年龄相关的男性常见病、多发病，40—70岁的男性中52%出现不同程度的ED症状。ED已成为影响男性健康的世界性问题，不仅在欧洲和北美急剧增加，而且在其它国家也明显增多，估计到     

勃起功能障碍的药物治疗进展

近年来,全球范围内勃起功能障碍（erectile dysfunction, ED）的发病率呈上升趋势,对于ED的发病机制及药物治疗研究有所进展。目前治疗ED的方法和药物越来越多,该文回顾总结近年来治疗ED的一线及二线药物的疗效及不良反应。     

伐地那非与勃起功能障碍

勃起功能障碍(ED)是与年龄相关的男性常见病、多发病。随着人们对ED机制研究的深入,磷酸二酯酶-5(PDE-5)抑制剂成为ED的一线治疗药物。本文就PDE-5抑制剂伐地那非的药理学特性、作用机制、临床疗效及安全性等问题进行综述。     

男性勃起功能障碍药物治疗临床研究进展

男性勃起功能障碍（ Erectile dysfunction,ED）是指阴茎持续不能达到或维持充分的勃起以获得满意的性生活，是男科常见的疾病，也是一种暴露性较差的疾病，绝大多数患者不主动求治 [1]。勃起是一个受心理因素和激素状态调节的神经血管活动过程。当受到性刺激时，神经冲动引起阴茎海绵体神经末梢释放神经递质和内皮细胞释放舒张因子（ EDRF/NO），使得小动脉平滑肌舒张，阴茎血流增加，阴茎海绵窦由于充血而膨胀，从而使阴茎勃起。同时，海绵体因充血膨胀，压迫白膜平滑肌，阻滞静脉回流，从而使勃起得以维持 [2]。从病理生理学角度可将 ED分为 3种主要类型：精神型 ED、器质型 ED（神经性的、激素性的、血管性的、海绵体性的或药物引起的）和精神－器质混合型 ED，其中混合型最为常见。不同类型的 ED具有不同的病因，因此需要采取不同的治疗措施。 ED分类、主要病变及病理生理学原因见表 1。     

治疗勃起功能障碍药物的研究现状与进展

综述治疗勃起功能障碍(ED)药物的研究情况.治疗ED的药物已应用于临床的有:①海绵体内注射药物,如罂粟碱、前列腺素E1等;②口服药物,如育亨宾、酚妥拉明、西地那非等;③经尿道给药,如前列地尔;④经阴茎皮肤给药,如硝酸甘油贴片等.另外,正在研究开发或试用于临床的有Melanotan Ⅱ,Vardenafil等.     

国内伐地那非治疗勃起功能障碍临床疗效的Meta分析

目的:系统评价国内伐地那非治疗勃起功能障碍的临床疗效。方法:计算机检索2004年～2009年6月CBMdisc、VIP、CNKI以及万方数据库等,获得5篇符合纳入标准的文献,对其进行Meta分析,并评价Meta分析结果的稳定性和发表偏倚。结果:异质性检验Chi-square=206.56,P<0.00001。采用随机效应模型进行Meta分析,合并WMD=9.64,95%CI为(8.92,10.35),总体效应检验,Z=26.44,P<0.00001,具有统计学意义。固定效应模型WMD值和95%CI与随机效应模型、剔除小样本后随机效应模型的结果基本一致,且本研究的发表偏倚得到了较好控制。结论:伐地那非能明显改善男性勃起功能障碍。     

男性抑郁症与勃起功能障碍共病分析

目的 探讨男性抑郁症患者与勃起功能障碍(ED)的共病情况及其影响因素.方法 对60例年龄26～50岁的男性抑郁症患者采用国际勃起功能指数问卷(IIEF-5)、汉米尔顿抑郁量表(HAMD)进行评估,同时对单相与双相抑郁患者组以及抑郁症与ED共病组及非共病组IIEF-5、HAMD量表评分进行比较,并对抑郁症与ED的共病的影响因素进行Logistic回归分析.结果 ①抑郁症患者与ED共病率为78.3%,主要为轻度ED;②双相抑郁患者与ED共病率以及IIEF-5与HAMD评分均显著高于单相抑郁患者;③21～30,31～40,41～50岁年龄段的抑郁症患者,其与ED共病率分别为65.5%、85.7%、85.0%,三者共病率比较有显著性差异.④服用SSRI类药物及米氮平的抑郁症患者,与ED共病率分别为77.5%及78.9%,两者比较无显著性差异;⑤HAMD评分＞17患者组的IIEF-5评分及与ED共病率均显著高于HAMD评分≤17患者组;⑥抑郁症与ED共病组HAMD量表评分显著高于非共病组;⑦Logistic回归分析表明HAMD评分及体重指数为抑郁症患者与ED共病的危险因素.结论 男性抑郁症患者与ED的共病率高,抑郁程度重及体重指数高可能是抑郁症患者与ED共病的危险因素.     

Population Dose-Response Model for Tadalafil in the Treatment of Male Erectile Dysfunction

PURPOSE: To determine the population dose-response relationship for tadalafil during on-demand (as-needed) administration for treatment of erectile dysfunction (ED). METHODS: A total of 212 male patients with mild, moderate, or severe ED participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive placebo or 2, 5, 10, or 25 mg tadalafil, taken on demand over an 8-week period. Efficacy was assessed on the basis of questions 2 and 3 of the Sexual Encounter Profile (SEP) and questions 3 and 4 of the International Index of Erectile Function (IIEF) questionaires. These scores were modeled using logistic regression. A fifth patient response, the IIEF EF (erectile function) domain score, was modeled as a continuous variable. RESULTS: The dose-response relationship for each efficacy variable was best described with an Emax model, in which maximum effect increased with ED severity at baseline. Response scores increased substantially between 10 and 25 mg tadalafil doses, and the dose-response parameter estimates suggested possibly higher responses at even higher doses. CONCLUSIONS: Population dose-response modeling of all five oucome measures indicated that efficacy in all ED severity groups in the studied population generally increased across the 2 to 25 mg tadalafil dose range. Estimates of maximal improvement (Emax) in the IIEF EF domain score were 7.5, 11.4, and 16.3 points for patients with mild, moderate, and severe ED, respectively. Corresponding tadalafil doses to attain half-maximal improvement (ED50 estimates) were 4.7 mg, 7.1 mg, and 10.1 mg.     

男性勃起功能障碍药物他达拉非的合成研究进展

他达那非为一种高效、高选择性的磷酸二酯酶5抑制剂,是美国食品与药物管理局2003年批准用于治疗男性勃起功能障碍的第3代药物。该文介绍他达拉非的多种合成方法并进行了优缺点比较,试图寻找一条最适合的大规模生产工艺路线。     

Pharmacotherapy for women's sexual dysfunction

Background: Women's sexual function is known to be strongly influenced by mental health and relationship factors. Biological factors interrupting sexual function that might potentially be remedied by pharmacological agents are less clear. Objectives: To examine the role of medications for women's sexual dysfunction. Methods: Searches were done using Medline, Embase, Lilacs and Pubmed databases. Conclusions: Although drugs designed to boost initial sexual desire have been trialed, amelioration of reduced sexual arousability may be a more appropriate target. There is limited evidence of pharmacological benefit to arousability so far. Local oestrogen therapy benefits reduced genital vasocongestion from vulvar vaginal atrophy. Drugs acting to enhance the actions of nitric oxide or vasoactive intestinal polypeptide can only benefit reduced genital congestion: most women complaining of low arousal have normal genital vasocongestion in response to sexual stimulation. In the context of autonomic neuropathies, phosphodiesterase inhibitors may be indicated. Early results of sexual benefit from local administration of dihydroepiandrosterone allowing intracellular production of oestrogen and testosterone in genital tissues post menopause seem promising.     

Pharmacotherapy for sexual dysfunction in women

In the setting of multiple studies claiming a high prevalence of sexual problems amongst women, new conceptualisation of the sexual response in women and definitions of sexual dysfunction, which reflect the need for biopsychosocial management, are being developed. The biological underpinnings of the sexual response in women may be influenced by environmental factors, as well as by medications, disease processes and normative changes in endogenous hormones. Psychological factors can alter both the physiological processes and the experience of sexual response. The new models clarify the importance of sexual motivations other than desire, sexual arousability and subtypes of arousal disorder. The role of pharmacotherapy to potentially augment desire, arousability, genital congestion and to lessen the pain of chronic dyspareunia must be envisaged within the holistic biopsychosocial model.     

Pharmacotherapy of asthma

The pharmacotherapy of asthma is a complex and evolving topic. A detailed understanding of the pathophysiologic processes involved in the asthmatic response forms the basis for understanding the actions of drugs used to treat this condition. Likewise, a solid comprehension of the medicinal chemistry and pharmacologic properties of the numerous agents involved in the treatment of asthma is critical for rationalizing drug choices and understanding potential side effects. Asthma is addressed at several points in the PharmD curriculum at South University including in the Pathophysiology (quarter 2), Integrated Sequence III (quarter 6), and Critical Care (quarter 9) courses. Various teaching strategies are employed throughout, along with weekly case-based recitations. The content presented here includes a synopsis of the pathophysiology and pharmacology from our Integrated Sequence III block on inflammatory diseases and asthma. A short review of pertinent pathophysiology is followed by a detailed presentation on the various classes of asthma drugs which includes their chemistry, mechanism of action, pharmacokinetics, toxicity, and interactions. This presentation is designed to prepare students for asthma therapeutics, which follows next in the schedule. The complexities of asthma pharmacotherapy are stressed along with current controversies and future drug development.     

Erectile Dysfunction Symptoms in Polydrug Dependents Seeking Treatment

Objective: To assess erectile dysfunction (ED) symptom prevalence, sexual behavior conditions, and risk factors associated to ED in a male polydrug dependent sample. Methods: A cross-sectional design study was conducted with 102 substance-dependent male polydrug users who sought outpatient treatment in São Paulo, Brazil. Sociodemographic data, drug of choice, chronic disease questions, sexually transmitted infections, International Index of Erectile Function (IIEF) scale, Sexual Addiction Screening Test (SAST), and WHOQOL-Bref instrument were used. Results: The erectile dysfunction prevalence was 32.3% and it was related to the marital status (single) (p < 0.001), occupational status (fully unemployed) (p < 0.001), presenting a chronic disease (p = 0.027), and with types of sexual partnerships (occasional partner) (p < 0.001). Alcohol (73.5%), tobacco (79.4%), cannabis (83.3%), and cocaine (snorted 78.4% and smoked 42.2%) were the drugs of choice. The ED risk decreased when marital status was married (odds ratio = 3.2 CI95% 1.411–7.518) and with chronic disease (odds ratio 0.06 CI95% 0.00–0.97), while having occasional sexual partners increased 14 times ED risk (OR 14.0 CI95%1.62–122.18). There were no significant associations between quality of life, DOC and ED. Conclusion: Approximately one third of the substance dependents in this sample presented ED. There is a need to integrate psychiatric and clinical care in substance treatment services, and to improve the provision of sexual health care and support available for this population.     

Erectile Dysfunction among People Who Use Ketamine and Poly-Drugs

Despite the rise in recreational use of ketamine in Malaysia, there have been no studies of users or of the health-related consequences they face. This study was initiated to examine ketamine use and its health consequences. A structured questionnaire was used to elicit information. A final sample of 127 males was divided into persons who used only ketamine and those who were poly-drug users. Each group was further divided into long-period and short-period users. Urine toxicology screening for ketamine and other illicit drugs commonly used in Malaysia was also done. Our findings corroborate those of earlier studies that link ketamine use to urological problems such as frequent urination, dysuria, incontinence, painful bladder, nocturia, and urinary urgency. A new finding in this study is the significant association between ketamine use and erectile dysfunction, such that higher odds of reporting erectile dysfunction were linked to long-period users. Our findings strengthen the case for early intervention, as ketamine users are drawn from young and unmarried male participants. The association of ketamine use with erectile dysfunction, if substantiated, will help physicians in their diagnosis of erectile dysfunction, particularly among youths.     

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Pathophysiology of Voiding Dysfunction and Pharmacological Therapy

Normal lower urinary tract function consists of voiding and storage. During voiding, the pontine micturition reflex center orders the sacral parasympathetic nucleus to increase parasympathetic activity, resulting in urinary bladder detrusor contraction via activation of post-synaptic muscarinic receptors (M2/3) and in the relaxation of both urethral and prostatic smooth muscle by nitric oxide (NO). In addition, the rhabdosphincter relaxes by inhibition of the pudendal nucleus at the sacral portion. During the storage phase, increase in sympathetic activity relaxes the urinary bladder via activation of post-synaptic β³-receptors and in the contraction of both urethral and prostatic smooth muscles via α¹-adrenoceptor. Many factors influence voiding function, including lower urinary tract disorders (benign prostatic hyperplasia in males, urethral stricture) and neurological disorders (central and peripheral). Theories of pharmacotherapy for voiding dysfunction are 1) increase detrusor contractility and 2) decrease urethral resistance. The former includes agonists for muscarinic receptors and cholinesterase inhibitor; and the latter includes α¹-adrenoceptor antagonists, NO donors, benzodiazepines, baclofen, dantrolene, and boturinum toxin.