**6. Summary**

180 Urinary Incontinence

augmentation cystoplasty. This group emphasized clinical outcomes (e.g. maximum detrusor pressure and bladder volume capacity) and patient symptoms (e.g. incontinence episodes and number of pads). Other outcomes included a questionnaire that measured

Using a definition of success as a > 50% reduction in symptoms, one group found a 97%

The human detrusor muscle contains B2 and B3-adrenoceptors. Both receptors are thought to be involved in detrusor relaxation. Currently, there are a number of [beta] 3-adrenoceptor selective agonists being evaluated as potential treatment for OAB, including YM178 (mirabegron). Chapple et al (Chapple et al., 2008) conducted a clinical trial with mirabegron versus tolterodine and placebo in patients with OAB. Patients in the treatment arm had a statistically significant reduction in mean micturition frequency when compared to placebo. In addition, mirabegron was superior to placebo in regard to mean volume voided per micturition, mean number of incontinence episodes, nocturia episodes, urgency incontinence episodes, and urgency episodes per 24 hours. The drug was well tolerated, and the most commonly reported adverse effects were headache and gastrointestinal adverse

Many parts of the brain are activated during storage and voiding and there is increasing interest in centrally acting drugs which modulate the micturition reflex. (Andersson & Pehrson, 2003) Tramadol is an analgesic that is a weak μ-receptor agonist; however, it is metabolized to several different compounds, which inhibit serotonin (5-HT) and noradrenaline reuptake. (Grond & Sablotzki, 2004;Safarinejad & Hosseini, 2006) Both μreceptor agonist and amine reuptake inhibition are useful in the treatment of OAB. In a double-blind, placebo-controlled, randomized study, 76 patients were given 100 mg tramadol sustained release every 12 hours for 12 weeks. Tramadol significantly reduced the number of incontinence periods by 50% per 24 hours. The authors concluded that tramadol

Tachykinins such as substance P, neurokinin A (NKA), and neurokinin B (NKB) may play a role in OAB. Substance P has a specific receptor (NK1) that is expressed in the dorsal horn of the spinal cord and may play an important role in detrusor overactivity. (Grond & Sablotzki,

Aprepitant, an NK1 receptor antagonist, has been shown to significantly improve symptoms of OAB in postmenopausal women with a history of urgency incontinence or mixed incontinence in a small pilot. (Green et al., 2006) Aprepitant significantly decreased the average daily number of micturitions (−1.3 ± 1.9) compared with placebo (−0.4 ± 1.7). The

quality of life, and the evaluation of complications from the surgery.

effects. Further randomized trials will be needed to prove efficacy.

provided beneficial clinical and urodynamic effects.

success rate for AC. (Blaivas et al., 2005)

**5.5.1 Beta adrenoreceptor agonists** 

**5.5.2 Centrally acting drugs** 

**5.5.2.1 Tramadol** 

**5.5.2.2 Tachykinins** 

2004; Safarinejad & Hosseini, 2006)

**5.5 Future therapies** 

Overactive bladder (OAB) is a common medical condition, yet often undetected and undertreated despite the substantial impact on a woman's quality of life. The etiology of OAB is unclear, but several mechanisms may interplay and interconnected in contributing to the multi-symptom condition. Despite symptoms that often interfere with work, daily life, intimacy, and also cause embarrassment and diminished self-esteem, less than half of sufferers seek treatment from a licensed provider.

A working clinical diagnosis of OAB can usually be made simply by utilizing proper urinary questionnaires, urinary diaries or a thorough medical history and physical examination. Confirmation of diagnosis is most often achieved via a post-void residual, simply cystometry or multichannel urodynamic testing.

The primary goal of treatment of OAB is simply a reduction in urinary incontinence episodes. First-line therapy for OAB should include conservative options such as timed voiding and alterations in types and amount of fluid intake. Counseling patients on dietary and lifestyle modification will often improve their acute symptoms and decrease the number of voiding episodes per day. Other non surgical first line options include pelvic floor muscle training and/or biofeedback, both of which center around exercises designed to improve the function of the pelvic floor muscles. The primary limitations of behavioral therapy is the required long term patient commitment required for effectiveness.

Antimuscarinic (anticholinergic) drugs are the cornerstone of pharmacological treatment of OAB and provide a favorable efficacy/tolerability/safety profile. These result in decreased bladder contractions and thus reduced the symptoms of OAB. For patients who are not candidates for antimuscarinic (anticholinergic) therapy or have failed previous trials of other medical therapy, noninvasive electrical stimulation to the pelvic floor via neuromodulation may increase pelvic muscle contractions and decrease detrusor contractions . More aggressive nerve modulation and stimulation therapies include, sacral nerve stimulation or peripheral nerve stimulation , which can be considered in patients with refractory urge incontinence. Lastly, surgical options, including augmentation cystoplasty and detrusor myectomy have been developed for those in which all other treatment alternatives have been exhausted.

Lastly, there are promising new receptor-specific medical alternatives emerging and future studies will determine their place in the therapeutic arsenal.

Despite the prevalence of OAB, and the patients' lack of willingness to report their life altering symptoms, screening for OAB should be part of every woman's annual well woman visit. Health care providers need not shy away from urinary incontinence questionnaires, as straightforward diagnosis and OAB treatments are available. Although the primary treatment goal of OAB is the reduction in urinary incontinence episodes, to the patient, the most important measure is quality of life.

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**11** 

*3University of Porto,* 

*Portugal* 

**Biomarkers in the Overactive Bladder Syndrome** 

Overactive bladder (OAB) is a symptomatic complex affecting both men and women. The overall incidence is above 10% but may exceed 40% in the elderly population (Irwin et al., 2006; Irwin et al., 2009; Sexton et al., 2009a). OAB is defined by the International Continence Society (ICS) as a clinical syndrome characterized by urinary urgency, with or without incontinence, usually with frequency and nocturia (Abrams et al., 2002, 2003; Hashim & Abrams, 2007). Urgency, which is a storage symptom defined as a sudden compelling desire to pass urine difficult to defer, is the hallmark symptom as it is the only one that must be present in order to establish the diagnosis of OAB (Abrams et al., 2002, 2003). Several comorbidities are very common among OAB patients, including depression, insomnia and fractures (Coyne et al., 2008; Sexton et al., 2009a; Sexton et al., 2009b). The economic costs of OAB, associated with medical consultations, therapy and diminished productivity at work, may reach billions of dollars (Irwin et al., 2009) and will certainly increase with the

The true causes of urgency/OAB remain poorly understood. The difficulty in establishing animal models that accurately represent urgency/OAB still holds. It was originally thought that the origin of OAB could be ascribed to anomalies in the neuromuscular junction and myocites. More recent data indicate a strong involvement of bladder sensory mechanisms involving the urothelium and suburothelial afferent nerves. In addition, dysfunction of central nervous system centres that control the micturition reflex, including the Periaqueductal Gray (PAG) and pontine micturition centre, has been implicated in the

No cure exists for OAB. Management is initiated by exclusion of confounding diseases and by the introduction of conservative measures, including limiting fluid intake, avoiding caffeinated, acidic and carbonated drinks, weight reduction, smoke avoidance and bladder training. If bothersome OAB symptoms persist, patients are initiated on antimuscarinic

genesis of OAB (Fowler et al., 2008; Drake et al., 2010; Fowler & Griffiths, 2010).

**1. Introduction** 

\* Corresponding Author

demographic shift of an ageing population.

Célia Duarte Cruz1,2,3, Tiago Antunes Lopes2,3,4,

*1Department of Experimental Biology, Faculty of Medicine of Porto,* 

Carlos Silva2,3,4 and Francisco Cruz2,3,4,\*

*2IBMC – Instituto de Biologia Molecular e Celular,* 

*4Department of Urology, Hospital de S. João, Porto,* 

