Pharmacotherapy in detrusor underactivity: A new challenge for urologists and pharmacologists (from lab to clinic).
Pharmacol Rep. 2016 Mar 19;68(4):703-706
Authors: Juszczak K, Drewa T
Abstract
Higher incidence of functional urinary bladder dysfunction (detrusor overactivity – DO and detrusor underactivity – DU) occurs in elderly people. Effective therapy is widely used in patients with DO, in contrast DU seems to be a serious burden for the older population due to the lack of successful treatment. The aim of the study was to review the potential pharmacological targets in DU treatment in the animal model. This review is based on systemic literature research. The Medline/Pubmed, Scopus, Embase, and Web of Science databases were searched in order to identify original and review articles, as well as editorials relating to underactive bladder, detrusor underactivity. The following Medical Subject Headings (MeSH) terms were used to ensure the sensitivity of the searches: urinary bladder, animal models, humans and therapy. 19 papers met the criteria and were included for this review. 19 papers met the criteria and were included for this review. The pathophysiology of DU and its animal models were described. Moreover, the potential pharmacological targets in DU therapy were discussed, such as bombesin receptors, prostaglandin-, ATP-, NO-, CGRP-, SP-, Dopamine-, NGF-, M2-, and agrin-dependent pathways. In conclusion, due to the lack of effective treatment strategies in DU, further research is necessary. Close cooperation between urologists and pharmacologists should be maintained for optimal research on DU pharmacotherapy.
PMID: 27110877 [PubMed – as supplied by publisher]
Last Updated: July 27, 2020 by uabadmin
Re: The Overactive Bladder Progression to Underactive Bladder Hypothesis.
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A ventral root avulsion injury model for neurogenic underactive bladder studies.
Detrusor underactivity (DU) is defined as a contraction of reduced strength and/or duration during bladder emptying and results in incomplete and prolonged bladder emptying. The clinical diagnosis of DU is challenging when present alone or in association with other bladder conditions such as detrusor overactivity, urinary retention, detrusor hyperactivity with impaired contractility, aging, and neurological injuries. Several etiologies may be responsible for DU or the development of an underactive bladder (UAB), but the pathobiology of DU or UAB is not well understood. Therefore, new clinically relevant and interpretable models for studies of UAB are much needed in order to make progress towards new treatments and preventative strategies. Here, we review a neuropathic cause of DU in the form of traumatic injuries to the cauda equina (CE) and conus medullaris (CM) portions of the spinal cord. Lumbosacral ventral root avulsion (VRA) injury models in rats mimic the clinical phenotype of CM/CE injuries. Bilateral VRA injuries result in bladder areflexia, whereas a unilateral lesion results in partial impairment of lower urinary tract and visceromotor reflexes. Surgical re-implantation of avulsed ventral roots into the spinal cord and pharmacological strategies can augment micturition reflexes. The translational research need for the development of a large animal model for UAB studies is also presented, and early studies of lumbosacral VRA injuries in rhesus macaques are discussed.
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Re: The Underactive Bladder: A New Clinical Concept?
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Meningitis-retention Syndrome; A Case Report.
We report a case of meningitis-retention syndrome followed by urodynamic tests. A 48-year-old man was admitted to the hospital for an undiagnosed fever with headache and urinary retention. Aseptic meningitis was suspected according to cerebrospinal fluid analyses, and urodynamic test showed an underactive detrusor, leading to inadequate contraction of the bladder on voiding in spite of a normal sensation during bladder filling. Clean intermittent self-catheterization was required temporarily, but normal urinary voiding without the need for medication was restored in 2 weeks after discharge from the hospital, when urodynamic tests showed normal contractility of the bladder during voiding.
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Phasic changes in bladder compliance during filling cystometry of the neurogenic bladder.
OBJECTIVE: To investigate phasic changes during filling cystometry that most accurately represent detrusor properties, regardless of other factors affecting detrusor contractility.
METHODS: Seventy-eight patients (59 males, 19 females; mean age, 48.2 years) with spinal cord injuries were enrolled. Urodynamic studies were performed using a normal saline filling rate of 24 mL/min. We calculated bladder compliance values of the detrusor muscle in each of three filling phase intervals, which divided the filling cystometrogram into three phases referable to the cystometric capacity or maximum cystometric capacity. The three phases were sequentially delineated by reference to the pressure-volume curve reflecting bladder filling.
RESULTS: Bladder compliance during the first and second phases of filling cystometry was significantly correlated with overall bladder compliance in overactive detrusors. The highest coefficient of determination (r(2)=0.329) was obtained during the first phase of the pressure-volume curve. Bladder compliance during all three phases was significantly correlated with overall bladder compliance of filling cystometry in underactive detrusors. However, the coefficient of determination was greatest (r(2)=0.529) during the first phase of filling cystometry.
CONCLUSION: Phasic bladder compliance during the early filling phase (first filling phase) was the most representative assessment of overall bladder compliance during filling cystometry. Careful determination of early phase filling is important when seeking to acquire reliable urodynamic data on neurogenic bladders.
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Last Updated: July 27, 2020 by uabadmin
Pharmacotherapy in detrusor underactivity: A new challenge for urologists and pharmacologists (from lab to clinic).
Higher incidence of functional urinary bladder dysfunction (detrusor overactivity – DO and detrusor underactivity – DU) occurs in elderly people. Effective therapy is widely used in patients with DO, in contrast DU seems to be a serious burden for the older population due to the lack of successful treatment. The aim of the study was to review the potential pharmacological targets in DU treatment in the animal model. This review is based on systemic literature research. The Medline/Pubmed, Scopus, Embase, and Web of Science databases were searched in order to identify original and review articles, as well as editorials relating to underactive bladder, detrusor underactivity. The following Medical Subject Headings (MeSH) terms were used to ensure the sensitivity of the searches: urinary bladder, animal models, humans and therapy. 19 papers met the criteria and were included for this review. 19 papers met the criteria and were included for this review. The pathophysiology of DU and its animal models were described. Moreover, the potential pharmacological targets in DU therapy were discussed, such as bombesin receptors, prostaglandin-, ATP-, NO-, CGRP-, SP-, Dopamine-, NGF-, M2-, and agrin-dependent pathways. In conclusion, due to the lack of effective treatment strategies in DU, further research is necessary. Close cooperation between urologists and pharmacologists should be maintained for optimal research on DU pharmacotherapy.
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Last Updated: July 27, 2020 by uabadmin
The underactive bladder: detection and diagnosis.
The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the “underactive bladder” (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration.
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The vexing problem of underactive bladder in children: a viable alternative.
Last Updated: July 27, 2020 by uabadmin
Lower Urinary Tract and Sexual Dysfunction in Neurological Patients.
Background: Lower urinary tract dysfunction (LUTD) and sexual dysfunction (SD) are common in neurological patients due to a combination of lesions affecting relevant neural control, constraints imposed by sensorimotor and cognitive deficits and – particularly for SD – psychosocial consequences of chronic neurological disease. Summary: This review summarizes the etiology, diagnosis and treatment of LUTD and SD in neurological patients. Key Messages: LUTD may lead to serious health problems; both LUTD and SD significantly affect quality of life. Management of patients with spinal cord injury and dysraphism is undertaken in specialized centers according to established guidelines. Treatment of neurological patients with noncomplicated neurogenic LUTD or SD should preferentially be guided by a neurologist. Clinical Impact: For rational treatment of urinary symptoms, an accurate assessment is mandatory; the bladder and the sphincter need to be defined as normal, over- or underactive. Urodynamic testing is the gold standard for functional diagnosis; assessment of residual urine and uroflow are the minimal requirements before considering management. Dysfunction of desire, arousal and orgasm (ejaculation) may be diagnosed by medical history and are amenable to counselling and treatment, which is – in the case of erectile dysfunction – evidence based. Further high-quality studies are necessary to test the best approaches for diagnosing and managing particular types of neurogenic LUTD and SD in the different neurological patient populations. © 2014 S. Karger AG, Basel.
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Detrusor underactivity: Pathophysiological considerations, models and proposals for future research. ICI-RS 2013.
AIMS: Detrusor underactivity, resulting in either prolonged or inefficient voiding, is a common clinical problem for which treatment options are currently limited. The aim of this report is to summarize current understanding of the clinical observation and its underlying pathophysiological entities.
METHODS: This report results from presentations and subsequent discussion at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2013.
RESULTS AND CONCLUSIONS: The recommendations made by the ICI-RS panel include: Development of study tools based on a system’s pathophysiological approach, correlation of in vitro and in vivo data in experimental animals and humans, and development of more comprehensive translational animal models. In addition, there is a need for longitudinal patient data to define risk groups and for the development of screening tools. In the near-future these recommendations should lead to a better understanding of detrusor underactivity and its pathophysiological background. Neurourol. Urodynam. © 2014 Wiley Periodicals, Inc.
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