3/20/10. Prevalence of OAB Men: 16.0% Women: 16.9% Prevalence of OAB with incontinence (OAB wet) Men: 2.6% Women: 9.3% Dry. Population (millions) Wet

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2 Prevalence of OAB Men: 16.0% Women: 16.9% Stewart WF, et al. World J Urol. 2003;20: Prevalence of OAB with incontinence (OAB wet) Men: 2.6% Women: 9.3% Stewart WF, et al. World J Urol. 2003;20: Population (millions) Dry 10 5 Wet 0 Arthritis* Chronic sinusitis* Overactive bladder Hypertension* Hay fever/ allergic rhinitis* Heart disease* Diabetes* Chronic bronchitis* Asthma* Ulcer* *Adams PF, et al. Vital Health Statistics ; No 200: Stewart WF, et al. World J Urol. 2003;20:

3 3

4 69 not processed before end of study Processed N=10,161 1,326 of unknown eligibility -unable to contact ( n=407) -contacted but refused screening ( n=919) Screened N=8,835 6, 018 Ineligible Eligible N= 2, Refused Type II DM 4

5 40% 35% 30% 25% 20% 15% 10% 5% 0% 40% 35% 21% 4% > 20 % with DM Voiding Dysfunction (IPSS) 8% 42% 50% Mild (IPSS >7) Moderate (8-19) Severe (> 20) 5

6 Frequency of Urinary Incontinence 15% 23% 19% 17% Never < Months Monthly Weekly Daily 26% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 81% 13% 6% < 100mL ml > 250mL % of patients 60% 60% 50% 40% 30% 20% 16% 24% First urge 10% 0% <100 ml ml >250mL 6

7 5% < 550 ml > 550 ml 95% 7

8 Milsom I, et al. BJU Int. 2001;87: Symptom Assessment Symptoms Urge incontinence Stress incontinence Mixed Urgency (strong, sudden desire to void) Yes No Yes Frequency with urgency (>8 times/24 h) Yes No Yes Leakage during physical activity (eg, coughing, sneezing, lifting, etc). Amou nt of urinary leakage with each episode of incontinence Ability to reach the toilet in time following an urge to void No Yes Yes May be large (if present) Small Variable Variable Yes Variable Waking to pass urine at night Usually Seldom Maybe Abrams P, et al. Urology. 2003;61: Guerrero P, Sinert R. Available at: Steers WD, et al. In: Adult and Pediatric Urology. 4 th Ed. 2002: Available at: Accessed 2/1/06. 8

9 SUI Mixed Symptoms Mixed Incontinence OAB Symptoms UUI SUI = stress urinary incontinence UUI = urge urinary incontinence Wein A, Rackley, R. J of Urol Suppl;175:S5-S10. 9

10 Lateral hypothalamic projections A-δ Sympathetic: Detrusor relaxed Urethra closed Hypogastric nerve sympathetic ON T 11 - L 2 S 2-4 Storage B 3 Pudendal nerve Image used with permission of Karl Luber, MD. de Groat WC. Urology. 1997;50(Suppl 6A): Parasympathetic: Detrusor contracts Urethra opens T 11 - L 2 Micturition S 2-4 Image used with permission of Karl Luber, MD. de Groat WC. Urology. 1997;50(Suppl 6A):

11 Forebrain (Cortex/Hypothalamus) Cerebral vascular accidents Changes in processing Dysfunction at a variety of levels and through a number of mechanisms can disrupt the neuromuscular axis in favor of incontinence T 11 - L 2 S 2-4 Image used with permission of Karl Luber, MD. de Groat WC. Urology. 1997;50(Suppl 6A): Midbrain: Pontine Parkinson s disease T 11 - L 2 S 2-4 Image used with permission of Karl Luber, MD. de Groat WC. Urology. 1997;50(Suppl 6A): Segmental (Cord) Spinal cord injury T 11 - L 2 S 2-4 Image used with permission of Karl Luber, MD. de Groat WC. Urology. 1997;50(Suppl 6A):

12 T 11 - L 2 Bladder Detrusor muscle changes Receptor changes (atropine resistant) Calcium overload Changes in electrical conductivity β-adrenergic receptor dysfunction S 2-4 de Groat WC. Urology. 1997;50(Suppl 6A): Image used with permission of Karl Luber, MD. Activation of the bladder Excitation of the micturition reflex Sahai A, et al. Expert Opin Pharmacother. 2006;7(5): Pharmacologic Treatment 12

13 Contraction of the Bladder Release of ACh from cholinergic nerves Stimulation of muscarinic receptors of bladder muscle INHIBIT Contraction of the Bladder ACh from cholinergic nerves stimulate muscarinic receptors BLOCK stimulation of muscarinic receptors 13

14 Clinical Efficacy * * Percent of patients *Last 3- or 7-day diary Dose escalation Transdermal: no 3- or 7-day data Diokno AC, et al. Mayo Clin Proc. 2003;78: Dmochowski RR, et al. Urology. 2003;62: Zinner N, et al. J Urol. 2004;171: Haab F, et al. ICS Annual Congress Poster 272. Cardozo L, et al. ICI Annual Meeting Poster 141. Le TH, et al. Curr Opin Obstet Gynecol. 2005;17: Important Distribution Sites for Antimuscarinic Effects CNS Iris/ciliary body Lacrimal gland Salivary glands Heart Gallbladder Stomach Colon Bladder (detrusor muscle) Abrams P, Wein AJ. The Overactive Bladder A Widespread and Treatable Condition

15 M 1 : Brain (cortex, hippocampus), salivary glands, sympathetic ganglia M 2 : Heart, hindbrain, smooth muscle (human detrusor, 80%) M 3 : Smooth muscle (human detrusor, 20%), salivary glands, brain, eye (lens, iris) M 4 : Brain (forebrain, striatum) M 5 : Brain (substantia nigra), eye Percent incidence *12-week study Dose escalation Diokno AC, et al. Mayo Clin Proc. 2003;78: Dmochowski RR, et al. Urology. 2003;62: Zinner N, et al. J Urol. 2004;171: Halaska M, et al. World J Urol. 2003;20: Hill S, et al. J Pelvic Med Surg. 2004;10(Supp 1):S36. Haab F, et al. Eur Urol. 2005;47: Chapple C, et al. ICS Annual Congress Abstract 276. Le TH, et al. Curr Opin Obstet Gynecol. 2005;17:

16 * * *12-week study Percent incidence Diokno AC, et al. Mayo Clin Proc. 2003;78: Dmochowski RR, et al. Urology. 2003;62: Zinner N, et al. J Urol. 2004;171: Hill S, et al. J Pelvic Med Surg. 2004;10(Supp 1):S36. Steers W, et al. BJU Int. 2005:95: Chapple C, et al. ICS Annual Congress Abstract 276. Le TH, et al. Curr Opin Obstet Gynecol. 2005;17: Chapple CR, et al. Eur Urol. 2005;48: * * Percent incidence *12-week study Transdermal: no data Diokno AC, et al. Mayo Clin Proc. 2003;78: Halaska M, et al. World J Urol. 2003;20: Chapple C, et al. ICS Annual Congress Abstract 276. Le TH, et al. Curr Opin Obstet Gynecol. 2005;17: Chapple CR, et al. Eur Urol. 2005;48:

17 Bladder Basis of urge control: Normal reflex arc inhibits detrusor by voluntary contraction of distal urethral sphincter Pelvic floor muscles Andersson KE, et al. Pharmacol Rev. 2004;56:

18 * Reduction (%) n = 63 n = 65 n = 62 *P < 0.04 vs. drug, P < vs. control P = vs. control Burgio KL, et al. JAMA. 1998;280: Mean reduction in UI (%) Behavioral modifications Enhanced therapeutic effects Combined therapy Drug therapy Combined therapy P = P = UI: urge incontinence Burgio KL, et al. J Am Geriatr Soc. 2000;48:

19 Govier FE, et al. J Urol. 2001;165: Vandoninck V, et al. Neurourol Urodyn. 2003;22: Sacral Neurostimulation (InterStim ) 19

20 Brain Bladder-bladder reflex (-) (+) Bladder (+) Sacral nerve stimulation (+) (+) (+) Bladder-urethral reflex (+) (+) Andersson KE. Lancet Neurol. 2004;3:

21 Neurostimulation Device Abrams P, et al. BJU Int. 2003;91:

22 3 years 2 years 1.5 years Percent of patients n = 41 n = 29 n = 42 P < > 50% symptom reduction Siegel SW, et al. Urology. 2000;56:

23 Botox Presynaptic Nerve Terminal ACh ACh ACh Vesicles BT SNAP-25 Blocks ACh Fusion & Release Schulte-Baukloh H, Schobert J, Stolze T, et al. Neurourol Urodyn. 2006;25(2):

24 24

25 Diabetic ED 55 y/o man with 10 year history of type 2 diabetes complained of gradual onset of ED and worsening in the past 6 months. On Lipitor and Diovan Smoke 1 PPD for 20 years Tried Viagra 50 mg for 6 times without success 25

26 Classification of ED Organic Vasculogenic Hormonal Neurogenic Cavernosal (venogenic) Drug-induced Psychogenic Generalized unresponsiveness lack of arousability inhibition Situational Partner related Central inhibition Performance related Psychological disorder Diagnosis of ED PE Lab 26

27 Contribution of risk factors to ED Intensive Lifestyle Changes Improves ED 58 Effects of Intensive Lifestyle Changes on Erectile Dysfunction in Men. Esposito K et al. Journal of Sexual Medicine 2009 Jan; 6(1):

28 Treatments for ED Lifestyle Change!! Medications (PDE 5 inhibitors or MUSE) Vacuum Erectile Device Penile Injections Inflatable Penile Prosthesis Injection to my what? Rita Yee 28

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