1. Challenges in Managing Urge Incontinence/OAB in the Elderly Patient: Introduction and Overview of OAB

2. Demographics and Classification

3. OAB - Demographics 23 - 35 million sufferers in the US 23 - 35 million sufferers in the US - Fewer than half seek medical treatment - Prevalence increases with age - Patients often on multiple medications Over $1.1 billion in sales-2003 US Over $1.1 billion in sales-2003 US Patients over 60 years of age comprise a significant share of the OAB population Patients over 60 years of age comprise a significant share of the OAB population Treatment rates are lower than for other age groups Treatment rates are lower than for other age groups Patient population is unsatisfied with current treatment Patient population is unsatisfied with current treatment - Utilization rates of only 50% - Low refill rates among all drugs

4. Prevalence of OAB Age and Gender Stewart WF, et al. World J Urol. 2003;20:327-336. Prevalence of OAB Men: 16.0% Women: 16.9%

5. OAB Treatment Rates by Age Group Source: IMS Retail Perspective

6. Patient Persistency is Poor 35.2 million Prevalent patient pop., 2004 (NOBLE) 7.5 million 21% consult physicians 1.9 million Total patient population, 2004 1.24 million 35% dropout rate 25% consult physicians Actively treated patient population, 2004 0.83 million 33% compliance rate Persistant patient population, 2004

7. OAB Population - Considerations Data presented here may be conservative – estimates exist noting the OAB population in the U.S. is 50% larger than the data presented Data presented here may be conservative – estimates exist noting the OAB population in the U.S. is 50% larger than the data presented The elderly population will continue to increase at a greater rate than the general population The elderly population will continue to increase at a greater rate than the general population The 2006 Medicare Modernization Act may increase the availability of drugs to all Medicare patients The 2006 Medicare Modernization Act may increase the availability of drugs to all Medicare patients

8. DEFINITIONS EPIDEMIOLOGY CLASSIFICATION PHYSIOLOGY

9. OAB Symptom Definitions Urgency: a sudden compelling desire to pass urine that is difficult to defer Urgency: a sudden compelling desire to pass urine that is difficult to defer Urgency Urinary Inc. (UUI): involuntary leakage accompanied by or immediately preceded by urgency Urgency Urinary Inc. (UUI): involuntary leakage accompanied by or immediately preceded by urgency Frequency: 8 voids / day = normal Frequency: 8 voids / day = normal Nocturia: patient wakes one or more times at night to void (sleep before and after) Nocturia: patient wakes one or more times at night to void (sleep before and after) Abrams P, et al. Urology. 2003;61:37-49.

10. OAB Symptom Definitions Urinary Stress Incontinence (USI): urinary loss with effort Urinary Stress Incontinence (USI): urinary loss with effort Overflow Incontinence: urinary leakage with retention Overflow Incontinence: urinary leakage with retention OAB – WET: urgency, frequency, incontinence OAB – WET: urgency, frequency, incontinence OAB – DRY: no urinary incontinence OAB – DRY: no urinary incontinence Abrams P, et al. Urology. 2003;61:37-49.

11. Types of Incontinence/Etiology UrgeStressOverflowTransient Damage to bladder nerves Spinal cord Bladder Ca Multiple sclerosis ParkinsonsAlzheimersStrokeBPHOAB Weak pelvic floor muscle Multiple pregnancy Pelvic prolapse Weak bladder muscles Diabetes Bladder tumors Urinary stones Delirium Infection Atrophic urethritis Pharmacologic/ psychological Endocrine disorders Restricted mobility Stool impaction Steers WD, et al. In: Adult and Pediatric Urology. 4 th Ed. 2002:1115-1216. Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/uiwomen. Accessed 2/1/06.http://kidney.niddk.nih.gov/kudiseases/pubs/uiwomen.

12. What Is Overactive Bladder?

13. Symptom Spectrum of OAB

16. STORAGE

17. EMPTYING

18. STORAGEEMPTYING BLADDERBLADDER

19. STORAGEEMPTYING BLADDERBLADDER OUTLETOUTLET

20. STORAGEEMPTYING BLADDERBLADDER OUTLETOUTLET OVERACTIVE UNDERACTIVE OVERACTIVE URGE RETENTION STRESS OBSTRUCTION PRESSURE TOO MUCH PRESSURE TOO LITTLE RESISTANCE TOO LITTLE RESISTANCE TOO MUCH

21. STORAGEEMPTYING BLADDERBLADDER OUTLETOUTLET OVERACTIVE UNDERACTIVE OVERACTIVE URGE RETENTION STRESSOBSTRUCTION PRESSURE= TOO MUCHPRESSURE= TOO LITTLE RESISTANCE= TOO LITTLERESISTANCE= TOO MUCH SYMPTOMS: frequency, urge, nocturia, urge incontinence SYMPTOMS: hesitancy, nocturia, straining, overflow incontinence SYMPTOMS: cough, laugh, sneeze stress incontinence SYMPTOMS: hesitancy, straining, incomplete emptying, nocturia overflow incontinence

22. STORAGEEMPTYING BLADDERBLADDER OUTLETOUTLET OVERACTIVE UNDERACTIVE URGE RETENTION PRESSURE= TOO MUCH PRESSURE= TOO LITTLE UNDERACTIVE STRESS RESISTANCE= TOO LITTLE OVERACTIVE OBSTRUCTION RESISTANCE= TOO MUCH CAUSES: 1) idiopathic 2) neurogenic (central) 3) obstruction CAUSES: 1) medication–distention 2) neurogenic–peripheral 3) muscular CAUSES: 1) anatomic hypermobility 2) ISD CAUSES: 1) iatrogenic -surgery 2) neurogenic 3) anatomic atrophy-stenosis

23. OVERACTIVE UNDERACTIVE OVERACTIVE URGE RETENTION STRESSOBSTRUCTION PRESSURE= TOO MUCH PRESSURE= TOO LITTLE RESISTANCE= TOO LITTLERESISTANCE= TOO MUCH MEDICAL TREATMENT anticholinergics estrogens BEHAVIORAL THERAPY MEDICAL TREATMENT cholinergics(?) CIC MEDICAL TREATMENT alpha agonists estrogens MEDICAL TREATMENT alpha blockers STORAGEEMPTYING BLADDERBLADDER OUTLETOUTLET

24. OVERACTIVE UNDERACTIVE OVERACTIVE URGE RETENTION STRESSOBSTRUCTION PRESSURE= TOO MUCHPRESSURE= TOO LITTLE RESISTANCE= TOO LITTLERESISTANCE= TOO MUCH SURGICAL TREATMENT sacral nerve stimulator bladder augmentation SURGICAL TREATMENT sacral nerve stimulator SURGICAL TREATMENT pubovaginal sling bladder neck suspension collagen injection SURGICAL TREATMENT excision of lesion urethrolysis STORAGEEMPTYING BLADDERBLADDER OUTLETOUTLET

25. Storage and Voiding Symptoms StorageVoidingPostmicturition UrgencyHesitancy Terminal dribble Frequency Poor flow Postvoid dribble NocturiaIntermittency Sense of incomplete emptying Urgency incontinence Straining Stress incontinence Dysuria Symptoms Often Relate to Bladder and Prostate Abrams P et al. Neuro Urodyn. 2002;21:167-178.

26. Storage and Voiding Symptoms StorageVoidingPostmicturition UrgencyHesitancy Terminal dribble Frequency Poor flow Postvoid dribble NocturiaIntermittency Sense of incomplete emptying Urgency incontinence Straining Stress incontinence Dysuria Abrams P et al. Neuro Urodyn. 2002;21:167-178. Symptoms Often Relate to Bladder and Prostate

27. Why Do We Treat Men Differently Than Women When It Comes to Bladder Symptoms? Male Prostate OAB symptoms are the same; anatomy is different OAB symptoms are the same; anatomy is different In men, LUTS are often considered related to the prostate In men, LUTS are often considered related to the prostate

28. Wein, Exp. Opin. Invest. Drugs 10(1): 65-83, 2001 Atropa belladonna L-type Ca 2+ channel