Uckert Stefan, Stief Christian G
Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, 30625 Hannover, Germany.
Handb Exp Pharmacol. 2011(204):307-22. doi: 10.1007/978-3-642-17969-3_13.
To date, it is widely accepted that several disorders of the male and female urogenital tract, such as erectile dysfunction, bladder overactivity, urinary stone disease, the benign prostatic syndrome, as well as symptoms of female sexual arousal and orgasmic dysfunctions, can be therapeutically approached by influencing the function of the smooth musculature of the respective organs. To achieve a pronounced drug effect without significant adverse events, a certain degree of tissue selectivity is mandatory. Selective intervention in intracellular pathways regulating smooth muscle tone has become the most promising strategy to modulate tissue and organ function. Since the concept of taking a pill to relieve symptoms of lower urinary tract dysfunction is now widely accepted following the successes of phosphodiesterase 5 (PDE5) inhibitor treatment of erectile dysfunction, the treatment of urological diseases has focused on orally available drugs acting via influencing intracellular signaling pathways, thereby combining a high response rate with the advantage of an on-demand intake. Specifically, the use of isoenzyme-selective PDE inhibitors offers great opportunities in the medical treatment of various genitourinary diseases. These agents are regarded to be safe and to be efficacious, i.e., having a fast onset of drug action and an improved effect-to-side-effect ratio. As experience with this class of compounds and their use in urology is rapidly growing, basic and clinical research in this field will most likely expand the pharmacological armamentarium of innovative treatment options in the next few years. The purpose of this review is to summarize current, as well as potential, upcoming indications for the use of PDE inhibitors in the pharmacotherapy of male erectile dysfunction and lower urinary tract symptoms.
迄今为止,人们普遍认为,男性和女性泌尿生殖道的多种疾病,如勃起功能障碍、膀胱过度活动症、尿路结石病、良性前列腺综合征以及女性性唤起和性高潮功能障碍的症状,都可以通过影响相应器官平滑肌的功能来进行治疗。为了在不产生明显不良事件的情况下获得显著的药物效果,一定程度的组织选择性是必不可少的。对调节平滑肌张力的细胞内途径进行选择性干预已成为调节组织和器官功能最有前景的策略。自从磷酸二酯酶5(PDE5)抑制剂治疗勃起功能障碍取得成功后,服用药物缓解下尿路功能障碍症状的概念现已被广泛接受,泌尿外科疾病的治疗重点已转向通过影响细胞内信号通路起作用的口服药物,从而将高反应率与按需服用的优势相结合。具体而言,使用同工酶选择性PDE抑制剂在各种泌尿生殖系统疾病的医学治疗中提供了巨大的机会。这些药物被认为是安全有效的,即起效快且疗效与副作用比有所改善。随着对这类化合物及其在泌尿外科应用经验的迅速积累,该领域的基础和临床研究很可能在未来几年扩大创新治疗选择的药理学武器库。本综述的目的是总结PDE抑制剂在男性勃起功能障碍和下尿路症状药物治疗中的当前以及潜在的、即将出现的适应证。