Pharmacological approach to overactive bladder and urge urinary incontinence in women: an overview

Abstract

Besides life-style changes, electrical stimulation or surgery, pharmacological treatment is becoming the first-choice approach in women suffering from lower urinary tract symptoms (LUTS), including urge urinary incontinence (UUI) and overactive bladder (OAB). Several drugs for the treatment of bladder storage and voiding disorders are currently available and, in the near future, novel compounds with higher specificity for the lower urinary tract receptors will be accessible. This will bring optimization of therapy, reducing side effects and increasing compliance, especially in patients with comorbidities and in women. The purpose of this paper is to give an overview on the pharmacotherapy of two common inter-correlated urological conditions, UUI and OAB. The study was conducted by analyzing and comparing the data of the recent international literature on this topic. Advances in the discovery of pharmacological options have dramatically improved the quality of life of patients affected by incontinence, but further studies are needed to increase the effectiveness and safety of the therapies used in this field.

Introduction

Lower urinary tract symptoms (LUTS) include urge urinary incontinence (UUI) and overactive bladder (OAB). OAB is caused by a sudden involuntary contraction of the bladder detrusor muscle and symptoms include urinary urgency with or without urge incontinence, often associated with frequent micturition and nocturia with lack of infection or other pathologies. UUI is an involuntary loss of urine combined with a sudden sensation of urgency with or without detrusor instability [1].

Cheung et al. indicated a prevalence of 82.9% of urinary incontinence (UI) in OAB patients [2]. Urgency, frequency and nocturia are typical symptoms, present in almost 90% of patients, and OAB is often associated with comorbidities such as increased urinary tract and skin infections. Initial treatment includes behavior modification and antimuscarinics administration and, in the case of OAB associated with UUI, the therapy focuses on the reduction of incontinence episodes [3], [4], [5]. Drugs currently used in the treatment of OAB and UUI are listed in Table 1 and the recommended doses are shown in Table 2.

Bladder storage and voiding depend on the interaction between parasympathetic, sympathetic, somatic, and sensory nerves [6]. Parasympathetic nerves trigger the contraction of bladder detrusor muscle through the stimulation of both M₂ and M₃ muscarinic receptors by acetylcholine and of purinergic receptor (P2X1) by ATP, and they also relax the urethral smooth muscle through the action of nitric oxide (NO). In the bladder there is a greater expression of M₂-receptors (80%) compared to M₃-receptors (20%), but it has been shown that detrusor contraction is largely mediated by the M₃ receptor. In addition, the somatic pudendal nerve stimulates the striated muscle of the external urethral sphincter through nicotinic receptor stimulation [7], [8], [9] and sympathetic receptors expressed in human detrusor and urothelium are the α₁-adrenoceptor (α₁-ARs) and β-adrenoceptor (β-ARs) subtypes, β₁, β₂ and β₃ [10], [11].

Given the involvement of the parasympathetic system in the functionality of the lower urinary tract, the gold standard therapy for LUTS is represented by antimuscarinics, although these compounds are not selective for bladder receptors, which is the reason for their numerous side effects (Table 3) [12].