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Review

Managing urinary incontinence in women - a review of new and emerging pharmacotherapy

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Pages 1989-1997 | Received 02 Jun 2018, Accepted 02 Oct 2018, Published online: 10 Oct 2018

References

  • Abrams P , Cardozo L , Fall M , et al. The standardisation of terminology of lower urinary tract function. Report from the standardisation sub-committee of the ICS. Neurourol Urodyn. 2002;21(2):167–178.
  • Litwin MS , Saigal CS , Em Y , et al. Urologic diseases in America Project: analytical methods and principal findings. J Urol. 2005;173(3):933–937.
  • Ebbesen MH , Hunskaar S , Rortveit G , et al. Prevalence, incidence and remission of urinary incontinence in women: longitudinal data from the Norwegian HUNT study (EPINCONT). BMC Urol. 2013;13:27.
  • Cannon T , Chancellor M. Pharmacotherapy for stress urinary incontinence. Rev Urol. 2003;5:135–141.
  • Kirchin V , Page T , Keegan PE , et al. Urethral injection therapy for urinary incontinence in women. Cochrane Database Syst Rev. 2017.
  • Moldovan CP , Marinone ME , Staack A. Transvaginal retropubic sling systems: efficacy and patient acceptability. Int J Womens Health. 2015;7:227–237.
  • Kelleher CJ , Kreder KJ , Pleil AM , et al. Longterm health-related quality of life of patients receiving extendedrelease tolterodine for overactive bladder. Am J Manag Care. 2002;8:S616–S630.
  • Sacco E , Tienforti D , D’Addessi A , et al. Social, economic, and health utility considerations in the treatment of overactive bladder. Open Access J Urol. 2010;2:11–243.
  • Sacco E. Physiopathology of overactive bladder syndrome. Urologia. 2012;79:24–35.
  • Sacco E , Pinto F , Bassi P . Emerging pharmacological targets in overactive bladder therapy: experimental and clinical evidences. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19:583–598.
  • Sacco E , Bientinesi R . Innovative pharmacotherapies for women with overactive bladder: where are we now and what is in the pipeline? Int Urogynecol J. 2015;26:629–640.
  • Huang W , Zong H , Zhou X , et al. Efficacy and safety of Imidafenacin for overactive bladder in adult: a systematic review and meta-analysis. Int Urol Nephrol. 2015;47:457–464.
  • Song M , Kim JH , Lee KS , et al. The efficacy and tolerability of tarafenacin, a new muscarinic acetylcholine receptor M3 antagonist in patients with overactive bladder; randomised, double-blind, placebo-controlled phase 2 study. Int J Clin Pract. 2015;69(2):242–250.
  • Thiagamoorthy G , Cardozo L , Robinson D . Current and future pharmacotherapy for treating overactive bladder. Expert Opin Pharmacother. 2016;17:1317–1325.
  • Dmochowski RR , Staskin DR , Duchin K , et al. Clinical safety, tolerability and efficacy of combination tolterodine/pilocarpine in patients with overactive bladder. Int J Clin Pract. 2014;68(8):986–994.
  • Zacche MM , Giarenis I , Cardozo L . Phase II drugs that target cholinergic receptors for the treatment of overactive bladder. Expert Opin Investig Drugs. 2014;23:1365–1374.
  • Fujimura T , Tamura K , Tsutsumi T , et al. Expression and possible functional role of the beta3-adrenoceptor in human and rat detrusor muscle. J Urol. 1999;161:680–685.
  • Takeda M , Obara K , Mizusawa T , et al. Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods. J Pharmacol Exp Ther. 1999;288:1367–1373.
  • Igawa Y , Yamazaki Y , Takeda H , et al. Functional and molecular biological evidence for a possible beta3-adrenoceptor in the human detrusor muscle. Br J Pharmacol. 1999;126:819–825.
  • Sacco E , Bientinesi R , Tienforti D , et al. Discovery history and clinical development of mirabegron for the treatment of overactive bladder and urinary incontinence. Expert Opin Drug Discov. 2014;9(4):433–448.
  • Sacco E , Bientinesi R . Mirabegron: a review of recent data and its prospects in the management of overactive bladder. Ther Adv Urol. 2012 Dec;4(6):315–324.
  • Staskin D , Herschorn S , Fialkov J , et al. A prospective, double-blind, randomized, two-period crossover, multicenter study to evaluate tolerability and patient preference between mirabegron and tolterodine in patients with overactive bladder (PREFER study). Int Urogynecol J. 2018;29:273–283.
  • Chapple CR , Nazir J , Hakimi Z , et al. Persistence and adherence with mirabegron versus antimuscarinic agents in patients with overactive bladder: a retrospective observational study in UK clinical practice. Eur Urol. 2017;72:389–399.
  • Edmondson SD , Zhu C , Kar NF , et al. Discovery of vibegron: a potent and selective β3 adrenergic receptor agonist for the treatment of overactive bladder. J Med Chem. 2016;59:609–623.
  • Di Salvo J , Nagabukuro H , Wickham LA , et al. Pharmacological characterization of a novel beta 3 adrenergic agonist, vibegron: evaluation of antimuscarinic receptor selectivity for combination therapy for overactive bladder. J Pharmacol Exp Ther. 2017;360(2):346–355.
  • Merck Sharp & Dohme Corp . A study of the efficacy and safety of vibegron (MK-4618) in participants with overactive bladder (OAB). [cited 2018 Sep 30]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT01314872
  • Yoshida M , Takeda M , Gotoh M , et al. Vibegron, a novel potent and selective β3-adrenoreceptor agonist, for the treatment of patients with overactive bladder: a randomized, double-blind, placebo-controlled phase 3 study. Eur Urol. 2018;73(5):783–790.
  • Igawa Y , Michel MC . Pharmacological profile of β3- adrenoceptor agonists in clinical development for the treatment of overactive bladder syndrome. Naunyn Schmiedebergs Arch Pharmacol. 2013;386:177–183.
  • Boehringer Ingelheim . Study to determine pharmacodynamic effects and pharmacokinetics of KUC 7483 CL in patients with spinal cord injury and neurogenic detrusor overactivity. [cited 2018 Sep 30]. Available from: https://clinicaltrials.gov/ct2/show/NCT02259751
  • Ohlstein EH , von Keitz A , Michel MC . A multicenter, double-blind, randomized, placebo-controlled trial of the β3- adrenoceptor agonist solabegron for overactive bladder. Eur Urol. 2012;62:834–840.
  • Rosa GM , Ferrero S , Nitti VW , et al. Cardiovascular safety of beta3-adrenoceptor agonists for the treatment of patients with overactive bladder syndrome. Eur Urol. 2016;69:311–323.
  • Dmochowski R , Duchin K , Tremblay T , et al. Tolenix™ (THVD-201), a novel combination of muscarinic antagonist (tolterodine) and muscarinic agonist (pilocarpine), is efficacious in OAB with less dry mouth compared to tolterodine alone. 28 th Annual EAU Congress 15-19 March 2013, Milan
  • Abrams P , Kelleher C , Staskin D , et al. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony). Eur Urol. 2015;67:577–588.
  • Herschorn S , Chapple CR , Abrams P , et al. Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study). BJU Int. 2017;120:562–575.
  • Gacci M , Andersson KE , Chapple C , et al. Latest evidence on the use of phosphodiesterase type 5 inhibitors for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol. 2016;70:124–133.
  • Chen H , Wang F , Yu Z , et al. Efficacy of daily low-dose tadalafil for treating overactive bladder: results of a randomized, double-blind, placebo-controlled trial. Urology. 2017;100:59–64.
  • Giuliano FA , Lamb J , Crossland A , et al. A placebo-controlled exploratory study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with storage lower urinary tract symptoms associated with a clinical diagnosis of overactive bladder. BJU Int. 2010;106:666–673.
  • Owbotham M , Harden N , Stacey B , et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. 1998;280:1837.
  • Field MJ , Oles RJ , Lewis AS , et al. Gabapentin (neurontin) and S‐(+)‐3‐isobutylgaba represent a novel class of selective antihyperalgesic agents. Br J Pharmacol. 1997;121:1513–1522.
  • Hansen HC . Interstitial cystitis and the potential role of gabapentin. South Med J. 2000;93:238–242.
  • Carbone A , Palleschi G , Conte A , et al. Gabapentin treatment of neurogenic over-active bladder. Clin Neuropharmacol. 2006;29:206–214.
  • Chua ME , See MC 4th , Esmeňa EB, et al. Efficacy and safety of gabapentin in comparison to solifenacin succinate in adult overactive bladder treatment. Low Urin Tract Symptoms. 2018;10(2):135–142.
  • Marencak J , Cossons NH , Darekar A , et al. Investigation of the clinical efficacy and safety of pregabalin alone or combined with tolterodine in female subjects with idiopathic overactive bladder. Neurourol Urodyn. 2011;30(1):75–82.
  • Ch L , Hc K . Practical aspects of botulinum toxin-A treatment in patients with overactive bladder syndrome. Int Neurourol J. 2015;19:213–219.
  • Totaro A , Pinto F , Pugliese D , et al. Intraprostatic botulinum toxin type “A” injection in patients with benign prostatic hyperplasia and unsatisfactory response to medical therapy: a randomized, double-blind, controlled trial using urodynamic evaluation. Neurourol Urodyn. 2018;37(3):1031–1038.
  • Sacco E , Bientinesi R , Marangi F , et al. Patient-reported outcomes in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with intraprostatic OnabotulinumtoxinA: 3-month results of a prospective single-armed cohort study. BJU Int. 2012;110(11Pt C):E837–44.
  • Yc C , Tyagi P , Cc H , et al. Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using liposomes. J Urol. 2009;182:786–792.
  • Hc K , Ht L , Yc C , et al. Pilot study of liposome-encapsulated onabotulinumtoxinA for patients with overactive bladder: a single-center study. Eur Urol. 2014;65:1117–1124.
  • Rk P , K-E A . Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats. J Urol. 2002;168:1230–1234.
  • Namasivayam S , Eardley I , Jf M . Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat. BJU Int. 1999;84:854–860.
  • Rong W , Km S , Burnstock G . Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder. J Physiol. 2002;541:591–600.
  • Da C , Dunn PM , Zhong Y , et al. P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol. 2005;567:621–639.
  • Vlaskovska M , Kasakov L , Rong W , et al. P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci. 2001;21:5670–5677.
  • Bayliss M , Wu C , Newgreen D , et al. A quantitative study of atropine-resistant contractile responses in human detrusor smooth muscle, from stable, unstable and obstructed bladders. J Urol. 1999;162:1833–1839.
  • Hanno PM Afferent clinical data for lead candidate, af-219, demonstrate improvements in pain and urinary urgency in interstitial cystitis/bladder pain syndrome (IC/BPS) Afferent Pharmaceuticals [ online]. [cited 2018 Sep 30]. Available from: http://www.businesswire.com/news/home/20150226005187/en/Afferent-Clinical-Data-Lead-Candidate-AF-219-Demonstrate
  • Appel GB , Appel AS . Angiotensin II Receptor Antagonists: role in Hypertension, Cardiovascular Disease, and Renoprotection. Prog Cardiovasc Dis. 2004;47:105–115.
  • Juszczak K , Maciukiewicz P . The angiotensin II receptors type 1 blockage affects the urinary bladder activity in hyperosmolar-induced detrusor overactivity in rats: preliminary results. Adv Clin Exp Med. 2017;26(7):1047–1051.
  • Gyhagen M , Bullarbo M , Nielsen T , et al. The prevalence of urinary incontinence 20 years after childbirth: a national cohort study in singleton primiparae after vaginal or caesarean delivery. Bjog. 2013;120:144–151.
  • Opara JA , Socha T , Bidzan M , et al. Stress urine incontinence especially in elite women athletes extremely practicing sports. Arch Budo. 2011;7:OF227–OF231.
  • Stothers L , Friedman B . Risk factors for the development of stress urinary incontinence in women. Curr Urol Rep. 2011;12:363–369.
  • Jung SY , Fraser MO , Ozawa H , et al. Urethral afferent nerve activity affects the micturition reflex; implication for the relationship between stress incontinence and detrusor instability. J Urol. 1999;162:204–212.
  • Andersson KE , Ekman G , Henriksson L , et al. The effect of midodrine and its active metabolite ST 1059 on the human urethra in vitro and in vivo. Scand J Urol Nephrol. 1983;17:261–265.
  • Klarskov N , Scholfield D , Soma K , et al. Measurement of urethral closure function in women with stress urinary incontinence. JUrol. 2009;181:2628–2633, discussion 2633
  • Malallah MA , Al-Shaiji TF . Pharmacological treatment of pure stress urinary incontinence: a narrative review. Int Urogynecol J. 2015;26:477–485.
  • Klarskov N , Cerneus D , Sawyer W , et al. The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry. Neurourol Urodyn. 2018;37(1):244–249.
  • Maund E , Guski LS , Gøtzsche PC . Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports. Cmaj. 2017;6;189(5):E194–E203.
  • Chen HY , Chen WC , Lin YN , et al. Synergistic effect of vaginal trauma and ovariectomy in a murine model of stress urinary incontinence: upregulation of urethral nitric oxide synthases and estrogen receptors. Mediators Inflamm. 2014;2014:314846.
  • Canda AE , Cinar MG , Turna B , et al. Pharmacologic targets on the female urethra. Urol Int. 2008;80(13):341–354.
  • Chen HY , Lin YN , Chen YH , et al. Stress urinary incontinence following vaginal trauma involves remodeling of urethral connective tissue in female mice. Eur J Obstet Gynecol Reprod Biol. 2012;163(14):224–229.
  • Chen YH , Lin YN , Chen WC , et al. Treatment of stress urinary incontinence by cinnamaldehyde, the major constituent of the chinese medicinal herb ramulus cinnamomi. Evid Based Complement Alternat Med. 2014;2014:280204.
  • Wan X , Liu C , Chen Y , et al. Sulforaphane treatment of stress urinary incontinence via the Nrf2-ARE pathway in a rat model. Cell Physiol Biochem. 2017;44(5):1912–1922.
  • Kaspar JW , Niture SK , Jaiswal AK . Nrf2:iNrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med. 2009;47(16):1304–1309.
  • Keum YS , Choi BY . Molecular and chemical regulation of the Keap1-Nrf2 signaling pathway. Molecules. 2014;19(17):10074–10089.
  • Singh P , Sharma R , McElhanon K , et al. Sulforaphane protects the heart from doxorubicin-induced toxicity. Free Radic Biol Med. 2015;86:90–101.
  • Madersbacher H , Halaska M , Voigt R , et al. A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. BJU Int. 1999;84:646–651.
  • Nishijima S , Sugaya K , Kadekawa K , et al. Efficacy of propiverine, an anticholinergic agent, in young and old rats. Life Sci. 2011;89:456–459.
  • Nishijima S , Sugaya K , Kadekawa K , et al. Propiverine increases urethral wall catecholamine levels and bladder leak point pressure in rats. Int J Urol. 2016;23:93–99.
  • Sugaya K , Sekiguchi Y , Satoh T , et al. Effect of propiverine hydrochloride on stress urinary incontinence. Int J Urol. 2014;21:1022–1025.
  • Tomonori M , Momokazu G , Osamu Y , et al. Therapeutic effect of propiverine hydrochloride on mixed-type urinary incontinence in women: the female urgency and stress urinary incontinence study of propiverine hydrochloride trial. Int J Urol. 2018;25:486–491.
  • Khullar V , Hill S , Laval KU , et al. Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial. Urology. 2004;64:269–274.
  • Sacco E , Recupero S , Bientinesi R , et al. Pioneering drugs for overactive bladder and detrusor overactivity: ongoing research and future directions. World J Obstet Gynecol. 2015;4(2):24–39.
  • Andersson KE , Gratzke C , Hedlund P . The role of the transient receptor potential (TRP) superfamily of cation-selective channels in the management of the overactive bladder. BJU Int. 2010;106:1114–1127.
  • Bientinesi R , Mancuso C , Martire M , et al. KV7 channels in the human detrusor: channel modulator effects and gene and protein expression. Naunyn Schmiedebergs Arch Pharmacol. 2017;390(2):127–137.
  • Sacco E , Bientinesi R , Bassi P , et al. Pharmacological methods for the preclinical assessment of therapeutics for OAB: an up-to-date review. Int Urogynecol J. 2016;27(11):1633–1644.
  • Michel MC , Igawa Y . Therapeutic targets for overactive bladder other than smooth muscle. Expert Opin Ther Targets. 2015;19(5):687–705.
  • Mizutani H , Sakakibara F , Komuro M , et al. TAS-303, a novel selective norepinephrine reuptake inhibitor that increases urethral pressure in rats, indicating its potential as a therapeutic agent for stress urinary incontinence. J Pharmacol Exp Ther. 2018;366(2):322–331.

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