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Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials.评估 URO-902(hMaxi-K)基因通过膀胱内灌注或直接注射到膀胱壁在女性特发性(非神经性)膀胱过度活动症和逼尿肌过度活动症患者中的安全性和潜在活性:来自两项双盲、不平衡、安慰剂对照的随机 1 期试验。
Neurourol Urodyn. 2020 Feb;39(2):744-753. doi: 10.1002/nau.24272. Epub 2020 Jan 16.
2
Efficacy and Safety of Mirabegron versus Placebo Add-On Therapy in Men with Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Randomized, Phase 4 Study (PLUS).米拉贝隆治疗伴有下尿路症状的良性前列腺增生症患者的疗效和安全性:一项随机、4 期研究(PLUS)。
J Urol. 2020 Jun;203(6):1163-1171. doi: 10.1097/JU.0000000000000738. Epub 2020 Jan 2.
3
Safety and Efficacy of Mirabegron: Analysis of a Large Integrated Clinical Trial Database of Patients with Overactive Bladder Receiving Mirabegron, Antimuscarinics, or Placebo.米拉贝隆的安全性和疗效:接受米拉贝隆、抗毒蕈碱药物或安慰剂的膀胱过度活动症患者大型综合临床试验数据库分析。
Eur Urol. 2020 Jan;77(1):119-128. doi: 10.1016/j.eururo.2019.09.024. Epub 2019 Oct 18.
4
Association of Treatment With 5α-Reductase Inhibitors With Time to Diagnosis and Mortality in Prostate Cancer.5α-还原酶抑制剂治疗与前列腺癌诊断和死亡时间的关系。
JAMA Intern Med. 2019 Jun 1;179(6):812-819. doi: 10.1001/jamainternmed.2019.0280.
5
Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment.大鼠停用5α还原酶抑制剂治疗后持续性勃起功能障碍与治疗持续时间的关系
World J Mens Health. 2019 May;37(2):240-248. doi: 10.5534/wjmh.180082. Epub 2018 Dec 26.
6
Long-term safety and efficacy of antimuscarinic add-on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A multicenter, randomized study in Japan (MILAI II study).米拉贝隆单药治疗疗效不佳的膀胱过度活动症患者加用抗毒蕈碱药物的长期安全性和有效性:日本多中心、随机研究(MILAI II 研究)。
Int J Urol. 2019 Mar;26(3):342-352. doi: 10.1111/iju.13868. Epub 2018 Dec 13.
7
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Neurourol Urodyn. 2019 Jan;38(1):295-304. doi: 10.1002/nau.23852. Epub 2018 Oct 12.
8
Cardiovascular safety of mirabegron: analysis of an integrated clinical trial database of patients with overactive bladder syndrome.米拉贝隆的心血管安全性:膀胱过度活动症患者综合临床试验数据库分析
J Am Soc Hypertens. 2018 Nov;12(11):768-778.e1. doi: 10.1016/j.jash.2018.08.001. Epub 2018 Aug 10.
9
Re: Tamsulosin and the Risk of Dementia in Older Men with Benign Prostatic Hyperplasia.关于:坦索罗辛与老年良性前列腺增生男性患痴呆症的风险
Eur Urol. 2018 Oct;74(4):522-523. doi: 10.1016/j.eururo.2018.07.013. Epub 2018 Jul 26.
10
The effect of hexanic extract of Serenoa repens on prostatic inflammation: results from a randomized biopsy study.没食子酸正十六烷醇酯对前列腺炎症的影响:来自一项随机活检研究的结果。
World J Urol. 2019 Mar;37(3):539-544. doi: 10.1007/s00345-018-2409-1. Epub 2018 Jul 19.

下尿路药理学:下尿路症状治疗的最新进展

Pharmacology of the lower urinary tract: update on LUTS treatment.

作者信息

Abreu-Mendes Pedro, Silva João, Cruz Francisco

机构信息

Department of Urology in Hospital de São João, Alameda Professor Hernâni Monteiro, Porto, 4200-319, Portugal.

Department of Urology, Hospital São João, Porto, Portugal.

出版信息

Ther Adv Urol. 2020 May 13;12:1756287220922425. doi: 10.1177/1756287220922425. eCollection 2020 Jan-Dec.

DOI:10.1177/1756287220922425
PMID:32489425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7238773/
Abstract

The number of compounds used in the pharmacological treatment of lower urinary tract symptoms (LUTS) of patients who do not respond to conservative measures has been relatively stable during the last decade, with the exception of the introduction of the new class of β3 adrenoceptor agonists. However, different combinations have been investigated, and the long-term use of these compounds has raised new concerns about adherence and safety. This review summarizes the current state of pharmacology for LUTS, and presents a thorough discussion of the possible challenges concerning their future use. In this narrative review, we analyze the most recent articles related to LUTS pharmacotherapy, after an initial review of mechanisms of bladder function relevant in present clinical practice. The main problems with pharmacotherapy in LUTS are associated with its moderate efficacy, low persistence on treatment, and the incidence of short- and long-term adverse events (AE) associated with some compounds. The long-term AE, such as cognitive impairment in the elderly vulnerable patients associated with antimuscarinic drugs or persistent erectile dysfunction in sexually active men after treatment with 5-α-reductase inhibitors (5-ARI), are some of the problems addressed in this review. Combination therapy taking advantage of the synergistic mechanisms of action between some classes of compounds may overcome AE associated with dose escalation. LUTS pharmacotherapy offers moderate results to most patients but not a full cure. The use of combination drugs to achieve better clinical results, reduce AE and improve both efficacy and adherence, will be used more frequently in the future. The recently raised concern on potential long-term irreversible AE associated with some of these drugs, like antimuscarinics and 5-ARI, are critically important and require further investigation.

摘要

在过去十年中,除了新型β3肾上腺素能受体激动剂的引入外,用于药物治疗对保守治疗无反应的下尿路症状(LUTS)患者的化合物数量相对稳定。然而,已经研究了不同的组合,这些化合物的长期使用引发了关于依从性和安全性的新问题。本综述总结了LUTS的药理学现状,并对其未来使用可能面临的挑战进行了全面讨论。在这篇叙述性综述中,我们在初步回顾当前临床实践中相关膀胱功能机制后,分析了与LUTS药物治疗相关的最新文章。LUTS药物治疗的主要问题与其疗效中等、治疗持续性低以及与某些化合物相关的短期和长期不良事件(AE)发生率有关。长期不良事件,如抗毒蕈碱药物导致老年易损患者认知障碍或5-α还原酶抑制剂(5-ARI)治疗后性活跃男性持续性勃起功能障碍,是本综述所探讨的一些问题。利用某些类化合物之间协同作用机制的联合治疗可能克服与剂量增加相关的不良事件。LUTS药物治疗对大多数患者的效果中等,但无法完全治愈。未来将更频繁地使用联合药物以获得更好的临床效果、减少不良事件并提高疗效和依从性。最近对与其中一些药物(如抗毒蕈碱药物和5-ARI)相关的潜在长期不可逆不良事件的关注至关重要,需要进一步研究。