EFFECT OF DISTIGMINE AT 5 mg DAILY IN PATIENTS WITH DETRUSOR UNDERACTIVITY

Sugaya, Kimio; Kadekawa, Katsumi; Onaga, Tomohiro; Ashitomi, Katsuhiro; Mukouyama, Hideki; Nakasone, Kei; Shimabukuro, Hiroichi; Shimabukuro, Shuichi; Matayoshi, Yukihide; Hokama, Seitetsu; Touyama, Yuichi; Nishijima, Saori

doi:10.5980/jpnjurol.105.10

Cited by 10 publications

(5 citation statements)

References 13 publications

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“…ASP8302 was shown to improve UI symptoms in males; the M3‐PAM mechanism may increase the resting tonus of bladder outlet smooth muscle during storage leading to a more efficient closure of the bladder outlet and/or preventing postvoid dribble. The cholinesterase inhibitor distigmine has been suggested to improve UI by increasing the tone of the urethral sphincter 18,19 . Cholinergic agonists did not show a clear effect on urethral pressure in females with UI, 18,20 which could explain the lack of improvement on UI in females.…”

Section: Discussionmentioning

confidence: 93%

“…The cholinesterase inhibitor distigmine has been suggested to improve UI by increasing the tone of the urethral sphincter. 18,19 Cholinergic agonists did not show a clear effect on urethral pressure in females with UI, 18,20 which could explain the lack of improvement on UI in females. No such data are available in the literature, specifically in males with UI to verify the above hypothesis.…”

Section: Discussionmentioning

confidence: 97%

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Muscarinic‐3‐receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial

Till

Arita

Kuroishi

et al. 2022

Neurourology and Urodynamics

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The aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3-PAM), in patients with underactive bladder (UAB). Methods: A randomized, double-blind, placebo-controlled multicenter study was performed in adult male/female subjects with UAB, defined as incomplete bladder emptying (postvoid residual volume [PVR] > 100 ml) without significant bladder outlet obstruction and/or overactive bladder. Subjects were randomized (1:1) to receive 4-week oral once-daily administration of 100 mg ASP8302 or matching placebo. Primary endpoint was a change from baseline in PVR measured by catheterization after standardized bladder filling (PVR C2 ). Other endpoints included PVR and bladder voiding efficiency (BVE) measured in various ways, uroflowmetry, bladder diary, and questionnaires. Pressureflow studies were performed in a subgroup.Results: One hundred and thirty-five patients were randomized (ASP8302 group: 65 patients, placebo group: 70 patients). The median change in PVR C2 was −40.0 ml (ASP8302) versus −35.0 ml (placebo) and the difference between groups was −5.0 ml (p = 0.960). In males, functional and symptomatic outcomes improved, for example, maximum urine flow rate (Q max ) and detrusor pressure at Q max (P det.Qmax ) increased (mean difference in change ASP8302 vs. placebo: 3.8 ml/s, p = 0.031 and 12.7 cm H 2 O, p = 0.034, respectively). Urinary incontinence episodes/24 h decreased in males with preexisting incontinence (mean difference: −0.35; p = 0.028). The incidence of adverse events was similar between study groups (ASP8302: 33.3%, placebo: 31.4%). In the included subjects, both baseline urine flow and bladder voiding pressure was low. Compared with PVR, simultaneous BVE measurements were more consistent between various methods (spontaneous vs. standardized bladder filling, catheterization vs. ultrasound [US]).

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Muscarinic‐3‐receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial

Till

Arita

Kuroishi

et al. 2022

Neurourology and Urodynamics

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“…Для стимуляції нейромедіаторної і нейром'язової провідності та скорочення гладких м'язів хворим ІІ групи спостереження призначали іпідакрин -20 мг 3 рази на добу протягом 4 тиж, механізм дії якого спрямований на блокаду калієвої проникності клітинної мембрани та зворотного пригнічення холінестерази [13].…”

Section: матеріали та методиunclassified

Rehabilitation of Patients with Benign Prostate Hyperplasia with Urinary Bladder Decompensation

Sarychev

Savchenko

Sarychev

et al. 2021

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The article is devoted to the problem of bladder decompensation and related complications in patients with BPH. The objective: to study the effectiveness of certain methods of restoring the functional capacity of the detrusor in patients with BPH with bladder decompensation. Materials and methods. The results of treatment of 149 patients with BPH with bladder decompensation aged 47 to 83 years (68,3±7,9) were analyzed, the proportion of which was 39,11 % of the total number of operated on BPH. Two groups of patients were formed by random sampling – every 2–3 patients. Group I included 30 people who underwent cystostomy. Group II included 30 people who, in addition to cystostomy, underwent metabolic-corrective and anticholinesterase therapy. The complex of drugs included B vitamins: octothiamine – 25 mg, riboflavin – 2,5 mg, pyridoxine hydrochloride – 40 mg, cyanocobalamin – 0,25 mg 3 times a day for 4 weeks; Anticholinesterase drug – ipidacrine 20 mg 3 times a day for 4 weeks. Results. According to the results of pathomorphological examination in both groups of observation there was desquamation of the urothelium, growth of connective tissue, bundles of nerve fibers with the phenomena of dystrophy. Degenerative changes in smooth muscle cells were accompanied by a decrease in the proportion of muscle tissue and a decrease in the diameter of leiomyocytes. However, in patients who underwent preoperative metabolism-corrective therapy, the diameter of the lumen of the arterioles was 20.21 % larger (p<0,05), the wall thickness of the arterioles – 31,73 % smaller (p<0,05), the Kernogan index is 28,22 % lower (p<0,05), the diameter of the capillaries is 3,52 % higher (p>0,05). The diameter of leiomyocytes was 45,26 % larger (p<0,05), the proportion of connective tissue in the bladder wall – 29,14 % lower (p<0,05). Compared with patients who underwent only cystostomy, after metabolic-corrective and anticholinesterase therapy in the short and long postoperative period were better indicators of functional capacity of the detrusor. 6 months after the second stage of the operation according to uroflowmetry Qmax was higher by 32,92 % (p<0,05), Qave – higher by 62,27 % (p<0,05), IPSS – lower by 33,18 % (p<0,05) and the QoL index is better by 29,54 % (p<0,05). Conclusions. Bladder decompensation due to untimely removal of the obstructive component is the main cause of unsatisfactory treatment results in patients with BPH. Anticholinergic exercise may be an additional factor in bladder decompensation in patients with BPH. Metabolism-correcting and anticholinesterase therapy permit to restore detrusor function by eliminating microcirculatory disorders and energy deficiency, stimulating neurotransmitter, neuromuscular conduction and smooth muscle contraction. In patients with megacystis, additional surgical correction by duplication allows the bladder to be emptied.

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“…Cholinesterase inhibitors might inhibit degradation of acetylcholine and provide beneficial effects for patients with UAB or DU. However, adverse events such as frequent defecation, fecal incontinence, diarrhea and frequent urination might bother patients [ 15 ]. Furthermore, these pharmacological treatments might not be suitable for patients with detrusor hyperactivity and inadequate contractility, in whom overactive symptoms are exacerbated after pharmacological treatment.…”

Section: P Harmacotherapy For Underactive Bladder or Detrusmentioning

confidence: 99%

Current pharmacological and surgical treatment of underactive bladder

2017

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Underactive bladder (UAB) or detrusor underactivity (DU) is a common yet still poorly understood urological problem. In addition to true detrusor failure and neuropathy, the inhibitory effects of detrusor contraction by the striated urethral sphincter and the bladder neck through alpha-adrenergic activity may also play a role in the development of UAB or DU. Treatment of UAB or DU aims to reduce the postvoid residual (PVR) urine volume and increase voiding efficiency, either by spontaneous voiding or abdominal straining. Pharmacotherapy with parasympathomimetics or cholinesterase inhibitors might be tried, and benefits can be achieved in combination with alpha-blockers. Bladder outlet surgeries, including urethral onabotulinumtoxinA injection, transurethral incision of the bladder neck, and transurethral incision or resection of the prostate can effectively improve voiding efficiency and decrease the PVR in most patients with DU. The mechanisms have not been well elucidated. It is likely that ablation of the bladder neck or prostatic urethra might not only decrease bladder outlet resistance but also abolish the sympathetic hyperactivity which inhibits detrusor contractility in patients with idiopathic UAB or DU.

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EFFECT OF DISTIGMINE AT 5 mg DAILY IN PATIENTS WITH DETRUSOR UNDERACTIVITY

Cited by 10 publications

References 13 publications

Muscarinic‐3‐receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial

Muscarinic‐3‐receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial

Rehabilitation of Patients with Benign Prostate Hyperplasia with Urinary Bladder Decompensation

Current pharmacological and surgical treatment of underactive bladder

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