妇科下尿路功能障碍141例尿动力学分析

目的探讨尿动力学在妇科下尿路功能障碍检查中的应用价值。方法对2009年1月至2010年9月我院141例下尿路功能障碍的妇科患者进行尿动力学检查,其中尿失禁106例,排尿困难14例,尿频21例。结果 106例尿失禁患者中,10例膀胱过度活动,42例未诱导出漏尿,22例膀胱流出道Linp-URR图示梗阻;14例排尿困难的患者中,1例膀胱过度活动,2例逼尿肌收缩乏力,5例检出漏尿,7例膀胱流出道Linp-URR图示无梗阻;21例尿频患者中,6例膀胱过度活动,4例顺应性欠佳,8例漏尿,无逼尿肌收缩乏力病例,5例膀胱流出道Linp-URR图示梗阻。尿失禁组患者的膀胱容量和最大尿流率明显高于排尿困难组和尿频组(P<0.05)。结论根据尿动力学检查结果有助于诊断并明确妇科下尿路功能障碍产生的原因。     

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.     

Emerging drugs for treatment of overactive bladder and detrusor overactivity

Background: Overactive bladder (OAB) signifies the presence of urinary urgency and can have major effects on quality of life and social functioning. Standard antimuscarinic drugs have good initial response rates but substantial adverse effects and long-term compliance problems. Objectives: To review the complexities of the mechanisms underlying OAB and the current drugs available for treating its symptoms. Methods: The literature was reviewed to define current therapies and drugs in clinical trials. Articles were identified by means of a computerised PubMed and Cochrane Library search (using the following keywords: overactive bladder, detrusor overactivity, urgency and bladder), supported by a search of the PharmaProjects database. Conclusions: New drug classes, such as beta-3 adrenergic agonists, may work by reducing contractility or excitability of bladder muscle. Moderation of afferent activity may allow improved OAB symptoms, with lower risk of affecting voiding function. Agents acting on the CNS could influence OAB favourably, but target selection and adverse effects are an issue. The recognition of the functional contribution of the urothelium and the diversity of nerve transmitters has sparked interest in both peripheral and central modulation of OAB pathophysiology.     

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Pathophysiology and Pharmacotherapy of Overactive Bladder

Overactive bladder (OAB) syndrome, which is characterized by a complex of storage symptoms (urinary urgency, frequency, nocturia, and urgency incontinence) is highly prevalent within the general population, causing major distress to patients in terms of their psychosocial and physical functioning. Muscarinic receptors of bladder smooth muscles are involved in both normal and disturbed bladder contraction. The muscarinic receptor functions may change in bladder disorders associated with OAB, implying that mechanisms, which normally have little clinical importance, may be up-regulated and contribute to the pathophysiology of OAB. In addition, several reports have suggested that various stimulations release many substances, including adenosine triphosphate, prostaglandins, nitric oxide, and acetylcholine, from bladder urothelium, which contribute to pathophysiology of the increased bladder sensation, OAB symptoms, and detrusor overactivity. Bladder urothelium possesses a non-neuronal cholinergic system and high density of muscarinic receptors. The roles and functions of the non-neuronal cholinergic system in OAB are now being evaluated. In the pharmacotherapy of OAB, antimuscarinic agents are the first choice drugs. Furthermore, new therapeutic targets at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord, and brain are proposed. In this review, the pathophysiology of OAB, especially the role of non-neuronal acetylcholine, is discussed. In addition, new drugs with new action mechanisms will be introduced.     

In vitro and in vivo effects of endothelin-1 and YM598, a selective endothelin ET A receptor antagonist, on the lower urinary tract

We investigated the contractile response of the lower urinary tract to endothelin-1 in vitro (rabbits) and in vivo (dogs). We also assessed the effects of a selective endothelin ET_A receptor antagonist, (E)-N-[6-methoxy-5-(2-methoxyphenoxy)[2, 2′-bipyrimidin]-4-yl]-2-phenylethenesulfonamide monopotassium salt (YM598), on endothelin-1-induced contractile responses. In the in vitro study, endothelin-1 induced contractile responses in isolated rabbit bladder base, urethra, and prostate tissues. YM598 (10^− 7–10^− 5 M) antagonized these endothelin-1-induced contractile responses without affecting the maximal responses. In the in vivo study, endothelin-1 induced the elevation of non-prostatic urethral pressure as well as prostatic urethral pressure even in the presence of tamsulosin (10 μg/kg, i.v.) in anesthetized male dogs. YM598 (0.1–3 mg/kg, i.v.) inhibited these endothelin-1-induced contractile responses in a dose-dependent fashion. These results suggest that endothelin ET_A receptors play an important role in the lower urinary tract contraction, and that the selective endothelin ET_A receptor antagonist YM598 has ameliorating effects on various urinary dysfunctions, including benign prostatic hyperplasia.