Practical Approaches to The Management of Overactive Bladder

1. Practical Approaches to The Management of Overactive Bladder Donald A. Culley MD, PhD, FACS South Atlanta Urology and Gynecology

2. Bladder Properties • Bladder is one of the most compliant organs of the body • Should provide perfect continence • Voluntary and efficient emptying at low pressure

3. Micturition Cycle • Fill and store • Empty completely - simple but important phases - important to help classify and treat disorders of micturition

4. Bladder Filling and Storage • Accommodates large volumes of urine - maintains low intravesical pressure (< 12 cm water) - sustains sensation that is appropriate • No involuntary contractions - hyperreflexia, overactivity, reflex contractions or instability • Maintain a closed and continent outlet at rest even with sudden intra-abdominal forces

5. Bladder Emptying • Bladder contraction - adequate magnitude - sustained to empty • Coordinated urethral relaxation - bladder neck and proximal urethral smooth muscle - striated external urethral sphincter • No anatomic obstruction

6. Parasympathetic Muscarinic Receptors • M1- neuronal, brain • M2- cardiac, detrusor • M3- detrusor, gastrointestinal smooth muscle, salivary glands • M4 + M5 • M3 receptors (20%) responsible for smooth muscle contraction • M2 receptors (80%) responsible for inhibition of smooth muscle relaxation

7. Overactive Bladder • Clinical term used to describe symptoms of frequency, urgency, +/- urge incontinence - term used without knowing specific cause of symptoms (eg, detrusor overactivity) • ICS 2002–Urgency with or without urge incontinence, usually with frequency and nocturia - absence of pathologic or metabolic conditions that might explain these symptoms

8. Overactive Bladder Pathophysiology • Multifactorial disorder • A constellation of functional abnormalities • 90% of cases idiopathic • Can be caused by: - neurologic defects - myogenic defects

9. Overactive Bladder Neurologic Defects • CVA • Dementia (eg, vascular disease, Alzheimer’s, encephalitis) • Cerebral palsy • Brain tumor • Parkinson’s disease • Multiple sclerosis • Shy-Drager syndrome

10. Overactive Bladder and Spinal Cord Injury • Complete suprasacral lesions above T7 - detrusor hyperreflexia - smooth sphincter dyssynergia - striated sphincter dyssynergia - no sensation • Complete suprasacral lesions below T7 - detrusor hyperreflexia - smooth sphincter synergy - striated sphincter dyssynergia - no sensation

11. Overactive Bladder Patient Evaluation • History • Physical • Urodynamics • Cystoscopy

12. History • Urologic • Ob/Gyn • Neurologic • Medical/surgical • Social/psych • Radiation • Pelvic trauma

13. Incontinence History • Characterization of incontinence • Length and severity of symptoms • Impact on quality of life • Associated bowel problems

14. Physical Exam Women • Systematic vaginal and pelvic exam - condition of mucosa - urethral mobility (Q tip test) - demonstration of continence (CST) - vaginal prolapse (anterior wall, posterior wall, apical) - bimanual exam

15. Physical Exam • Men–DRE and urogenital exam • Neurologic exam - mental status - mobility - lumbar and sacral sensory and motor eg, BC reflex, anal wink, knee and ankle DTR’s

16. Ancillary Tests • Voiding and intake diary - Extremely important especially in cases of overactive bladder • Incontinence diary • Urine analysis - urine culture and cytology when indicated • Post void residual • Pad test

17. Role of Cystometry • Defining underlying pathophysiology - bladder filling - involuntary detrusor contractions - low bladder compliance - urethral obstruction - impaired detrusor contractility • Directing treatment

18. Pharmacologic Treatment of Bladder Overactivity • Decrease detrusor activity - abolish involuntary detrusor contractions - increase volume at which they occur - increase compliance • Increase bladder capacity • Commonly used agents focus on inhibition at the end organ level

19. Pharmacologic Agents Bladder Overactivity • Antimuscarinics • Muscle relaxants • Mixed action drugs • Tricyclic antidepressants • Alpha blockers • Beta agonists • Vasopressin analogues

20. Antimuscarinics • Antimuscarinics (anticholinergic) drugs have been the mainstay of medical therapy for bladder overactivity • Have been somewhat limited by the high incidence of side effects and lack of selectivity

21. Mechanism of Action of Antimuscarinics • Inhibit bladder contraction - ACh from cholinergic nerves stimulate muscarinic receptors - block stimulation of muscarinic receptors

22. Antimuscarinic Agents of Common Side Effects • Dry mouth • Constipation • Drowsiness/somnolence • Blurred vision/dry eyes

23. Antimuscarinics 2007 • Oxybutynin IR BID-TID • Oxybutynin ER QD • Oxybutynin TDS BIW • Tolterodine IR/ER BID/QD • Tropsium BID • Solifenacin QD • Darifenacin QD

24. What is the Difference? • Efficacy - no great differences - dose-dependent • Tolerability • Safety • Clinical effectiveness–different for different patients depending on expectations

25. Imipramine • Prominent systemic anticholinergic effects • Weak antimuscarinic effects on the bladder • Strong direct inhibitory effect on bladder smooth muscle which is not anticholinergic or adrenergic • Decreases contractility/increases outlet resistance • Effects on lower urinary tract are additive to those of atropine-like agents; useful in combo with other anticholinergics • Most common side effects - anticholinergic effects, weakness, fatigue, sedation

26. Combination Pharmacotherapy • Combination therapy–combining 2 drugs that have different actions, eg, anticholinergic and tricyclic • Intravesical instillation of Oxybutynin - works best in cases where oral form is effective but patients can’t tolerate side effects - requires self-catheterization

27. Evaluation of Refractory Overactive Bladder • Post void residual • Comprehensive urodynamic testing • Cystoscopy • Urine cytology • Upper tract study - renal ultrasound - CT/MRI - IVP • Neurological evaluation, if necessary

28. Refractory Detrusor Overactivity • Intravesical instillations–Capsaicin • Botulinum-A Toxin • Neuromodulation - efficacy in neurogenic overactivity not universally accepted • Urinary reconstruction - augmentation - diversion

29. Conclusion • Improved understanding of pathophysiology • Contribution of alternate neural receptors • Better understanding of receptor action and interaction • Mechanism of action of antimuscarinics and side effects