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Vol 85, No 3 (2014)
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The new era in the pharmacological treatment of overactive bladder (OAB): mirabegron – a new selective β3agonist

Tomasz Rechberger, Paweł Miotła, Andrzej Wróbel, Beata Kulik-Rechberger
DOI: 10.17772/gp/1716
·
Ginekol Pol 2014;85(3).

open access

Vol 85, No 3 (2014)
ARTICLES

Abstract

Overactive bladder is defined by ICS as urgency, frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection, or other obvious causative pathology. Lower urinary tract symptoms (LUTS) are highly prevalent, especially in aging populations. Epidemiological studies reported LUTS in 62% of men and 67% of women, rising to 81% and 79%, respectively in adults over 60 years old. However, the actual burden of LUTS remains relatively unrecognized. LUTS, mainly due to considerable distress including almost all aspects of social functioning, impact on sleep and mental health, may significantly affect quality of life. Management of LUTS including OAB has undergone dramatic changes since 1972, when the first antimuscarinic drug – oxybutynin, was introduced into clinical practice. In the last two decades, six new antimuscarinic drugs entered OAB field and this was accompanied by introduction of botulinum toxin into clinical practice in patients resistant to or not compliant with antimuscarinics. Nowadays, it is recognized that OAB is progressive, age-related and non sex-specific condition with most patients experiencing a combination of storage, voiding and post-micturition symptoms. In 2013, the next step was taken, with new therapeutic options for OAB, enabling an even more patient-tailored approach. This was possible for both, male and female OAB sufferers with new class of oral β3 adrenoreceptor agonist (mirabegron). This drug, by stimulation of β3-adrenoceptors, couples via Gs proteins to adenylyl cyclase, what results in an increase of intracellular cAMP levels and a subsequent activation of cAMP-dependent protein kinase A, which then phosphorylates myosin light chain kinase responsible for inhibition of calcium-calmodulin dependent interaction of myosin with actin. Moreover, the cAMP increase also leads to the reduction of cytoplasmic Ca2+ concentration by removal of calcium ions from cytoplasm. These both actions result in a significant increase in the storage bladder capacity and by this interval between micturitions is prolonged. Mirabegron was evaluated in three 12-week, double blind, randomized, placebo controlled, parallel-group, multicenter clinical trials in OAB patients with symptoms of urge urinary incontinence, urgency and frequency – study 046, 047 and 074. It should be pointed out that efficacy of mirabegron was maintained through the entire 12-month period in phase III long-term study. Discoveries on the physiology of the normal bladder and on the pathophysiology underlying OAB have led to the development of new treatment options for OAB. Pharmacological management of OAB should be tailored to patient’s characteristics. New and recent options of pharmacological treatment have undoubtedly expanded treatment possibilities, what should allow physicians to select the optimal treatment for each patient.

Abstract

Overactive bladder is defined by ICS as urgency, frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection, or other obvious causative pathology. Lower urinary tract symptoms (LUTS) are highly prevalent, especially in aging populations. Epidemiological studies reported LUTS in 62% of men and 67% of women, rising to 81% and 79%, respectively in adults over 60 years old. However, the actual burden of LUTS remains relatively unrecognized. LUTS, mainly due to considerable distress including almost all aspects of social functioning, impact on sleep and mental health, may significantly affect quality of life. Management of LUTS including OAB has undergone dramatic changes since 1972, when the first antimuscarinic drug – oxybutynin, was introduced into clinical practice. In the last two decades, six new antimuscarinic drugs entered OAB field and this was accompanied by introduction of botulinum toxin into clinical practice in patients resistant to or not compliant with antimuscarinics. Nowadays, it is recognized that OAB is progressive, age-related and non sex-specific condition with most patients experiencing a combination of storage, voiding and post-micturition symptoms. In 2013, the next step was taken, with new therapeutic options for OAB, enabling an even more patient-tailored approach. This was possible for both, male and female OAB sufferers with new class of oral β3 adrenoreceptor agonist (mirabegron). This drug, by stimulation of β3-adrenoceptors, couples via Gs proteins to adenylyl cyclase, what results in an increase of intracellular cAMP levels and a subsequent activation of cAMP-dependent protein kinase A, which then phosphorylates myosin light chain kinase responsible for inhibition of calcium-calmodulin dependent interaction of myosin with actin. Moreover, the cAMP increase also leads to the reduction of cytoplasmic Ca2+ concentration by removal of calcium ions from cytoplasm. These both actions result in a significant increase in the storage bladder capacity and by this interval between micturitions is prolonged. Mirabegron was evaluated in three 12-week, double blind, randomized, placebo controlled, parallel-group, multicenter clinical trials in OAB patients with symptoms of urge urinary incontinence, urgency and frequency – study 046, 047 and 074. It should be pointed out that efficacy of mirabegron was maintained through the entire 12-month period in phase III long-term study. Discoveries on the physiology of the normal bladder and on the pathophysiology underlying OAB have led to the development of new treatment options for OAB. Pharmacological management of OAB should be tailored to patient’s characteristics. New and recent options of pharmacological treatment have undoubtedly expanded treatment possibilities, what should allow physicians to select the optimal treatment for each patient.
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Keywords

Overactive Bladder, pharmacological treatment

About this article
Title

The new era in the pharmacological treatment of overactive bladder (OAB): mirabegron – a new selective β3agonist

Journal

Ginekologia Polska

Issue

Vol 85, No 3 (2014)

DOI

10.17772/gp/1716

Bibliographic record

Ginekol Pol 2014;85(3).

Keywords

Overactive Bladder
pharmacological treatment

Authors

Tomasz Rechberger
Paweł Miotła
Andrzej Wróbel
Beata Kulik-Rechberger

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