Faculty Disclosure. Objectives. Spectrum of Voiding Dysfunction. Types of Incontinence/Etiology. Urinary Incontinence Symptom Definitions

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1 Faculty Disclosure Strategies to Improve Adherence and Clinical Management of Overactive Bladder: Prevalence of OAB and Impact on Quality of Life Dr. Saffel has no actual or potential conflicts of interest in relation to this presentation. Dana Saffel, PharmD, CGP PharmaCare Strategies, Inc. Santa Rosa Beach, FL Objectives Spectrum of Voiding Dysfunction Recognize the prevalence of OAB and the impact of symptoms on quality of life. Develop effective treatment plans for older adults with overactive bladder. Evaluate the efficacy and safety of current and emerging therapies for adults with overactive bladder. Address the current long term care regulations for the evaluation and management of urinary incontinence. Minimize medication side effects in treatment plans for older adults with overactive bladder. SUI SUI stress urinary incontinence UUI urge urinary incontinence OAB overactive bladder Overactive Bladder z Mixed (UUI+SUI) UUI Urgency Frequency cturia Urinary Incontinence Symptom Definitions Urinary Stress Incontinence (USI): urinary loss with effort Overflow Incontinence: urinary leakage with retention Urge Urinary Incontinence: involuntary leakage of urine with or immediately preceded by urgency Transient or Functional Incontinence : inability to reach toilet due to mental or physical condition Overactive Bladder (OAB) - Urgency, with or without urge incontinence, usually with frequency and nocturia Abrams P, et al. Urology. 2003;61: Types of Incontinence/Etiology Urge Damage to bladder nerves Spinal cord Bladder Cancer Multiple sclerosis Parkinson s Alzheimer s Stroke BPH OAB Stress Multiple pregnancy Pelvic prolapse Overflow Weak pelvic floor Weak bladder muscle muscles Diabetes Bladder tumors Urinary stones Delirium Infection Transient Atrophic urethritis Pharmacologic/ psychological Endocrine disorders Restricted mobility Stool impaction Steers WD, et al. In: Adult and Pediatric Urology. 4 th Ed. 2002: Available at: Accessed 2/1/06. Page 1

2 Differential Diagnosis: Overactive Bladder, Stress Incontinence, and Mixed Symptoms Common Geriatric Diseases that Affect Continence Medical History and Physical Examination Symptom Assessment Symptoms OAB SUI Abrams P, Wein AJ. The Overactive Bladder A Widespread and Treatable Condition Mixed Symptom s Urgency (strong, sudden desire to void) Frequency with urgency (> 8 times/24 h) Leaking during physical activity (eg, coughing, sneezing, lifting) Amount of urinary leakage with each episode of incontinence Large (if present) Small Variable Ability to reach the toilet in time following an urge to void Often no Variable Waking to pass urine at night Usually Seldo m Maybe Vaginal atrophy NF Prevalence: >90% Effect: inflammation, tenderness, friability of vaginal & urinary tract tissues causing frequency & urgency Diabetes NF Prevalence: 32% Effect: osmotic diuresis, neuropathy CHF NF Prevalence: 22% Effect: diuresis BPH NF Prevalence: >90% Effect: bladder spasms resulting from obstruction & incomplete bladder emptying UTI NF Prevalence: 10% Effect: bladder irritation with frequency & urgency Incidence Under-reported Which of the following descriptions best describes OAB? A. Urine leakage during stressful activities (i.e., laughing, sneezing, jumping, bending) B. Urine leakage occurring during or immediately after a strong urge to void C. Urgency and frequency without urine loss D. A & B E. A & C Increasing incidence in an aging population but < 50% with bladder control problems report it to their health care provider Due to: Embarrassment Low expectation for therapy Belief it s normal part of aging Availability of absorbent products/pads Fear of having to move from ALF Impact of Urinary Incontinence on Quality of Life Neural Control of the Lower Urinary Tract Occupational Absence from work Decreased productivity Domestic Requirements for specialized underwear, bedding Sexual Avoidance of sexual contact and intimacy Ko y. Am J Manag Care Jul;11(4 Suppl):S Quality of Life Physical Limitations or cessation of physical activities Social Reduction in social interaction Alteration of travel plans Increased risk of institutionalization of frail older persons Psychological Guilt/depression Loss of self-respect and dignity Fear of: being a burden lack of bladder control urine odor Apathy/denial Β-3 receptors NE M3 receptors M2 receptors M2 receptors ACh NE ACh α receptors ACh = acetylcholine. N receptors Andersson K-E, Hedlund P. Urology. 2002;60(suppl 5A): Page 2

3 Distribution and Function of Muscarinic Receptors Throughout the Body* M 1 M 2 M 3 Location Cerebral cortex, hippocampus, salivary glands, eye Smooth muscle, hippocampus, hindbrain, cardiac muscle, eye, bladder Smooth muscle, salivary glands, eye, brain, bladder M 4 Basal forebrain striatum, salivary glands Unknown Function Memory and cognitive function, saliva and tear secretion Heart rate, tear secretion Bladder contraction, bowel motility, saliva and tear secretion, visual accommodation M 5 Substantia nigra, eye Visual accommodation What receptor(s) that are involved with relaxing the bladder wall to allow for urine storage? A. M2 B. M3 C. β3 D. A& B E. All of the above *Muscarinic receptors are expressed in all tissues. Andersson K-E. Lancet Neurology. 2004;3:46-53; Andersson K-E, Yoshida M. Eur Urol. 2003;43:1-5; Chapple CR et al. Urology. 2002;60(suppl 5A):82-89; Choppin A, Eglen RM. Br J Pharmacol. 2001;132: ; Collison DJ et al. Invest Opthalmol Vis Sci. 2000;41: ; Dean B et al. CurrMol Med. 2003;3: ; Kanno H et al. Am J Physiol Cell Physiol. 2003;284:C988 C998; Igawa Y. Urology. 2000;55(suppl 5A):47-49; Seeger T et al. J Neurosci. 2004;24: ; Gautam G et al. Mol Pharmacol. 2004;66: ; Anagnostaras S et al. Nature Neurosci. 2002;6:51-58; Wess J. Annu Rev Pharmacol Toxicol. 2004;44: Effective Methods of Treating OAB Treatment for OAB Pads Behavioral therapy Medications Neuromodulation Surgery Combined pharmacologic and behavioral therapy provides improved outcomes 1,2 1. Mattiasson A. Neuro Urodyn. 2001;20: Burgio et al. JAGS. 2000;48: Behavioral Modification Diet Modification Pelvic floor exercises Education/Log Behavioral Modification Timed voiding Delayed voiding Avoid food/beverages irritating to the bladder (coffee, caffeine, etc.) Manage fluid intake Stop evening fluids Avoid constipation Diet Sandip P. Urinary Incontinence Managemeng & Treatment. emedicine.medscape.com/article/ treatment Sandip P. Urinary Incontinence Managemeng & Treatment. emedicine.medscape.com/article/ treatment Page 3

4 Bladder Training Behavioral Modification Modify bladder function Methods bladder diary gradually increase void interval teach coping strategies Strengthen pelvic floor muscles and improving bladder stability 197 women with urge incontinence Modified crossover design Initially on monotherapy of either Behavioral therapy Drug therapy (oxybutinin mg/d) Combined therapy offered after 8 weeks if not content with monotherapy alone Sandip P. Urinary Incontinence Managemeng & Treatment. emedicine.medscape.com/article/ treatment Burgio et al. JAGS. 2000;48: Behavioral Modification Behavioral therapy 57.5% reduction in incontinence 8 patients crossed over 88.5% reduction in incontinence when meds added (p=0.034) Medical therapy 72.7% reduction in incontinence 27 patients crossed over 84.3% reduction in incontinence when meds added (p=0.001) Conclusion: combining drug & behavioral therapy in a stepped program can produce added benefit for patients with UUI Behavior modification for the management of urinary incontinence includes which of the following? A. Clothes with elastic waist for quick & easy removal B. Pelvic floor muscle strengthening C. Delayed voiding D. A & B E. B & C Burgio et al. JAGS. 2000;48: Medication Modification Medication Modification (cont) Alcohol Medication Class α-receptor agonists α-receptor antagonists ACE inhibitors Anticholinergics Antidepressants, tricyclic Medications Effecting Lower Urinary Tract Function Polyuria, frequency, UUI Effect on LUT Urethral constriction and urinary retention (males), OFI Urethral relaxation, SUI Cough SUI Urinary retention, fecal impaction, OFI Anticholinergic effect, OFI -α-receptor antagonist effect,sui Medications Effecting Lower Urinary Tract Function Medication Class Effect on LUT β-receptor agonists Urinary retention, OFI Calcium channel blockers Urinary retention, fecal impaction, OFI Opioids Urinary retention, fecal impaction, OFI Sedative-hypnotics Sedation, delirium, muscle relaxation, UUI Diuretics Polyuria, frequency, urgency, UUI Methylxanthines Polyuria, bladder irritation, UUI Neuroleptics Anticholinergic effect, sedation, OFI LUT lower urinary tract UUI urge urinary incontinence LUT lower urinary tract UUI urge urinary incontinence OFI overflow incontinence SUI stress urinary incontinence OFI overflow incontinence SUI stress urinary incontinence Page 4

5 Pharmacologic Therapy for the Treatment of OAB Antimuscarinic agents have been the mainstay for treating OAB Treatment can be limited by side effects such as dry mouth, GI effects (eg, constipation), and CNS effects (cognitive impairment) Newest OAB agent is first-in-class Beta-3 agonist Avoids anticholinergic side effects OAB symptoms relieved by Inhibition of involuntary bladder contractions Increased bladder capacity M1 Muscarinic Receptor Distribution Dizziness Somnolence Impaired memory and cognition CNS M2 Iris/ciliary body Lacrimal gland Salivary glands Heart Stomach and esophagus Colon Dry mouth Constipation Blurred vision Dry eyes M1,M2, M3&M5 Tachycardia Dyspepsia M3 M1&M3 M2 M3 Abrams P, Wein AJ. The Overactive Bladder A Widespread and Treatable Condition Bladder (detrusor muscle) M2&M3 Ideal Muscarinic Receptor Antagonist Efficacious inhibits involuntary bladder contractions does not adversely affect volitional detrusor activity Organ selective preferentially affects the bladder over other organs results in minimal side effects and improved tolerability Durable effects improves compliance and/or persistency Provides clinical effectiveness the optimal balance of efficacy, tolerability, and compliance/persistency Drug Darifenacin (Enablex) 7., 1 ER Fesoterodine (Toviaz) 4mg, 8mg ER Oxybutynin (Ditropan) tab Oxybutynin LA (Diitropan XL), 10mg, 1 Oxybutynin gel (Gelnique) 3%, 10% Oxybutynin Patch (Oxytrol Rx) (Oxytrol for Women - OTC) 3.9mg Antimuscarinic Agents for OAB Receptor Specificity M3 selective Initial 7. 4mg - TID 84mg 3.9mg twice weekly Max 1 8mg QID 30mg 84mg 3.9mg twice weekly Generic? Month Cost for Initial $150 $150 $20 (generic) $75 (generic) $175 $225 (Rx) $15 (OTC) Medications for Overactive Bladder. Pharmacist s Letter. PL Document # October Side Effects (max % prevalence) Dry mouth (35%), constipation (21%), dizziness(2%) abnormal vision (<2%) Dry mouth(35%), constipation(6%), fatigue, dizziness, blurred vision(<1%) Dry mouth(71%), constipation(13%), dizziness(16%), somnolence(13%), blurred vision(9%) Dry mouth(61%), constipation(13%), somnolence(12%), dizziness(6%), blurred vision(8%) Dry mouth(12%), application site reactions (5%), blurred vision, constipation, pruritus (<2%) Application pruritus (14%), dry mouth (4%), constipation(3%), abnormal vision(2.5%), fatigue, somnolence, headache (<2%) Antimuscarinic Agents for OAB (con t) Beta-3 Agonist Agent for OAB (con t) Drug Solifenacin (Vesicare), 10mg tab Tolterodine (Detrol) 1mg, 2mg tab Tolterodine LA (Detrol LA) 2mg, 4mg, ER cap Trospium (Sanctura) 20mg tab Trospium LA (Sanctura XR) 60mg ER cap Receptor Specificity Initial 1mg 2mg 20mg 60mg Max 10mg 2mg 4mg 20mg 60mg Generic? Month Cost for Initial $190 $120 (generic) $174 $100 $190 Side Effects (max % prevalence) Drug mouth(28%), constipation(13%), blurred vision(5%), fatigue(2%) Dry mouth(35%), constipation(7%), fatigue(4%), dizziness(5%) Dry mouth(23%), constipation(6%), somnolence (3%), fatigue(2%), dizziness(2%), abnormal vision(1%) Dry mouth(20%), constipation(10%), blurred vision(<1%) Dry mouth(10%), constipation(9%), blurred vision, somnolence (<1%) Drug Mirabegron (Myrbetriq) 2, 50mg ER tab Receptor Specificity Beta-3 agonist Initial 2 Max 50mg Generic? Month Cost for Initial $210 Side Effects (max % prevalence) Hypertension(7.5%), headache(3.2%), constipation, arthralgia, diarrhea, tachycardia, abdominal pain, fatigue (all <2%) Medications for Overactive Bladder. Pharmacist s Letter. PL Document # October Medications for Overactive Bladder. Pharmacist s Letter. PL Document # October Page 5

6 Choosing OAB Therapy Choosing OAB Therapy All antimuscarinic agents have Level 1 evidence; Grade A recommendation Choice depends on cost, availability, efficacy, tolerability, side effects Extended release versions of oxybutynin and tolterodine are marginally more efficacious than the immediate release but have fewer adverse events Trospium, theoretically, does not cross the blood-brain barrier and thus may be advantageous in the elderly and those who operate machinery Oxybutynin patch is transdermal and is advantageous in those on oral polypharmacy or those who do not like taking tablets or cannot tolerate them. A version is available OTC Mirabegron avoids common anticholinergic side effects and may be a good alternative for patients with cognitive impairment or chronic constipation Which of the following OAB products causes the fewest anticholinergic side effects? A. Oxybutynin B. Fesoterodine C. Mirabegron D. Tolterodine E. Trospium Which OAB treatment is available as an OTC product? A. Oxybutynin gel B. Oxybutynin patch C. Mirabegron tab D. Solifenacin tab E. Trospium tab What If Oral Pharmacotherapy Fails? If one antimuscarinic fails, for any reason, then it is advisable to try a different one after about 6-8 weeks of therapy. Some would recommend trying three and others would recommend trying all available OAB medications before urodynamics. If the above fails then a specialist opinion should be sought to perform urodynamics and provide further treatment. Page 6