1. Urine for a treat (sorry)
Jamie McCarrell, Pharm.D., BCPS, BCGP

2. URINARY INCONTINENCE

3. Learning Objectives
Given a patient case, create an appropriate treatment plan for a patient with each of the following:
Urge urinary incontinence (UUI)
Stress urinary incontinence (SUI)
Overflow incontinence (OI)
Identify common side effects of the medications used to treat incontinence

4. UI Prevalence Under-reported Documented Rates of Incontinence
59% of affected delay reporting for 1 year or more
25% delay reporting for over 5 years
Documented Rates of Incontinence
43-60% in nursing homes
35% in the acute care setting
8-34% in the community
Increasing rates with increasing age
M=F for overactive bladder (OAB) – 16%
Higher rates of OAB with incontinence in women

5. Impact of UI Quality of Life Health Utilities Index (HUI) scoring*
Health-related Quality of Life (HRQL)**
 healthcare seeking behaviors
 HRQL, mental health, work productivity
Overwhelmingly negative
ALZ UI
0.0
1.0
Dead
Perfect Health
Stroke
*Bartoli S, et al. Urology. 2010;75:
**Coyne KS, et al. BJU Int. 2011;108:

6. Urinary Incontinence Classification
Overactive bladder (OAB)
Detrusor contracts during filling phase
Urge Urinary Incontinence
Urethra or urethral sphincters cannot sufficiently impede urine flow
Stress Urinary Incontinence
Combination of UUI and SUI
Mixed
Bladder underactivity
Bladder outlet obstruction (BOO)
Overflow Incontinence
Unrelated to urethral or bladder capability
Functional

7. Urinary Incontinence Classification

8. Causes and Precipitating Factors
UUI
(Myogenic versus neurogenic)
Idiopathic
Increasing age
Neurologic disorders
BOO
Hysterectomy
Recurrent UTIs
SUI
Pregnancy
Childbirth (vaginal delivery)
Menopause
Cognitive impairment
Obesity OI
Bladder underactivity
Functional
Many, but not intrinsic damage to or malfunction of the urinary tract
Myogenic – the overactive bladder and UUI result from changes within the smooth muscle of the bladder wall itself
Neurogenic – ascribes the condition to disease related changes within the central or peripheral nervous systems.

9. Urge Urinary Incontinence
Overactive bladder (OAB)
Symptoms
Urinary frequency (more then 8 times/day) and urgency (sudden compelling desire to urinate that is difficult to delay)
Nocturia (>1 micturition/night) and/or enuresis (nocturnal incontinence)
Volume usually large due to complete emptying of the bladder

10. Stress Urinary Incontinence
Urethral/internal sphincter underactivity
Symptoms:
UI during activities that increase the intraabdominal pressure
Running, coughing, sneezing, lifting
Usually small volume, proportional to the level of activity

11. Overflow Incontinence
Bladder is filled to capacity, but unable to empty
Bladder underactivity
Loss of function of the detrusor muscle
Bladder outlet obstruction
BPH, prostate cancer, diabetes, denervation
Symptoms
Difficulty initiating stream
Dribbling
Small amounts of urine leaking constantly

12. Nonpharmacologic Management
Lifestyle modifications
Weight loss improved mixed UI in obese women
Scheduling regimens – bladder training, etc.
Low quality evidence showed improvement in UUI
Dementia
Social implications
Pelvic floor muscle rehabilitation
>5 times as effective as no active treatment in improving SUI
Anti-incontinence devices/agents
Incontinence supplies
Surgery

13. Incontinence Supplies
Briefs, pads, various undergarments
Tons to choose from, combine, etc for optimal protection
Note – most Rx therapy will NOT restore continence, so these may be needed along with therapy
Two things to cause Dr. McCarrell to become angry:
“Diapers”
Skin Integrity
lose his

14. Summary of ACP Recommendations Non-Pharm
UUI
Bladder Training
Weight Loss if Obese
Pharmacologic Treatment
Drug choice patient-specific
SUI
Pelvic Floor Muscle Training
No Systemic Pharmacologic Therapy
Potentially topical estrogens
Mixed UI
WITH

15. Pharmacologic Options for UI
UUI
Solifenacin
Festerodine
Trospium chloride
Oxybutynin
Tolterodine
Darifenacin
Mirabegron
SUI
Duloxetine
Pseudoephedrine
Ephedrine
Estrogen (topical OI
Bladder underactivity
Self-catheterization
Bladder outlet obstruction (BOO)
Relieve the Obstruction

16. UUI Treatment Target
Muscarinic Control
Diagram:

17. Urge Urinary Incontinence
Treatment
Anticholinergic agents/antispasmodics
Mechanism of action
Antagonize muscarinic cholinergic receptors
Decrease parasympathetic nerve impulses to the detrusor muscle
First-line pharmacotherapy – improved quality of life
Agent within class chosen based on side effects and cost (as well as other considerations).
Most effective agents for suppression of premature detrusor contractions, enhancing bladder storage, and relieving symptoms
Adverse Effects: orthostatic hypotension, sedation, weight gain, dry mouth, constipation, confusion, hallucinations, tachycardia

18. Urge Urinary Incontinence
Treatment
Beta3 Agonist
Mechanism of action
Increases bladder storage capacity by activating beta-3 receptors and causing relaxation of the detrusor muscle
Newest class of medications for UUI
Consider for use in those intolerant of anticholinergic effects
Adverse effects: high blood pressure, tachycardia

19. Urge Urinary Incontinence Medications
Source: Lexi-Comp
Medication
MOA
Dosing
Comments
Toviaz®
Fesoterodine
Antimuscarinic
4 mg PO daily (can ↑ to 8 mg)
M3 preferred, $$$
Vesicare®
Solifenacin
5 mg PO daily (can ↑ to 10 mg)
Enablex®
Darifenacin
7.5 mg PO daily (can ↑ to 15 mg)
M3 specific, $$$
Sactura®
Trospium
IR: 20 mg BID
ER: 60 mg daily
1st semi-specific to be generic
Detrol®
Tolterodine
IR: 2 mg BID
ER: 4 mg daily
Can reduce dose if SEs
Ditropan®
Oxybutynin
IR: 5 mg 2-3x/d
ER: 5-10mg daily
TD: 3.9 mg Q3-4d
Gel: 3 pumps daily
Most SEs, many formulations, less cost
Myrbetriq®
Mirabegron
Beta-3 agonist
25 mg PO daily (can ↑ to 50 mg)
Potential for less SEs, $$$, still really new

20. Oxytrol® For Women Median episodes of daily UI episodes
Baseline: Transdermal oxybutynin 3.9 mg/day—4.0, placebo—4.0; 

Week 12: Transdermal oxybutynin 3.9mg/day—1.0, placebo—2.0.
39% of women with OAB don’t want to discuss their condition with anyone
33% have not discussed their condition with a healthcare professional (HCP)
Women typically have OAB for 4 years before talking to an HCP about it

21. Urge Urinary Incontinence
Treatment
Tricyclic antidepressants
Reserved for those with a concurrent indication
Peripheral neuropathy, depression
No more effective than oxybutynin IR
Adverse effects: orthostatic hypotension, cardiac conduction abnormalities, confusion
Overdose – potentially life-threatening
Desipramine and nortriptyline preferred due to ↓ side effects

22. Pharmacologic Options for UI
UUI
Solifenacin
Festerodine
Trospium chloride
Oxybutynin
Tolterodine
Darifenacin
Mirabegron
SUI
Duloxetine
Pseudoephedrine
Ephedrine
Estrogen (topical) OI
Bladder underactivity
Self-catheterization
Bladder outlet obstruction (BOO)
Relieve the Obstruction

23. SUI Treatment Target Adrenergic Control Non-Pharm Control
Diagram:

24. Stress Urinary Incontinence
Treatment
ACP guidelines recommend against treatment with pharmacologic therapy
Strong recommendation, low-quality evidence
Duloxetine (Cymbalta)
First-line therapy in EAU guidelines, with moderate benefit
Serotonin and norepinephrine have positive effects neuronal pathways of the micturition reflex
Dosing: 40 mg PO BID
Adverse effects: nausea, headache, insomnia
Diminish with time

25. Stress Urinary Incontinence
Treatment
Alpha-adrenergic agonists
Pseudoephedrine mg TID
Phenylephrine 10 mg four times daily
Benefit in mild or moderate SUI
Adverse effects: hypertension, headache, insomnia
Topical Estrogens
SUI in combination with urethritis or vaginitis due to estrogen deficiency

26. Pharmacologic Options for UI
UUI
Solifenacin
Festerodine
Trospium chloride
Oxybutynin
Tolterodine
Darifenacin
Mirabegron
SUI
Duloxetine
Pseudoephedrine
Ephedrine
Phenylpropanolamine
Estrogen (topical OI
Bladder underactivity
Self-catheterization
Bladder outlet obstruction (BOO)
Relieve the Obstruction

27. OI Treatment Target Muscarinic Overload Physical Block (Prostate?)
Diagram:

28. Overflow Incontinence
Bladder underactivity
Intermittent self-catheterization 3-4 times daily
Bethanechol mg PO 3-4 times/day
Cholinergic agonist
Short term use only
Avoid in asthma or heart disease
Remove anticholinergic agents
Bladder outlet obstruction (BOO)
Relief of the obstruction
Can be pharmacological – see treatment of benign prostatic hyperplasia

29. As you treat, prevent these:
Pendulum of Pee
Teeter Totter of Tinkle
Boomerang Bladder

30. Patient Case
TT is an 92 yo female who presents with complaints of urinary frequency (12x/24 h), urgency, and incontinence. She reports incontinence to occur 1-3 x/24 h, and is now wearing absorbent briefs.
What questions do you have for her?

31. Patient Case Continued
Leakage is not worsened by laughing, coughing, sneezing, or carrying heavy objects.
She denies feelings of incomplete voiding.
She is embarrassed, and has decreased her social activities significantly.
Non-pharmacological approaches have failed.

32. Asymptomatic Bacteriuria

33. Asymptomatic Bacteriuria
> 70 y.o.
15-20% prevalence for community,
25-50% prevalence for nursing home
Diagnosis:
WOMEN: 2 consec (+) cultures with ≥ 105 cfu/mL
MEN: Single, clean catch specimen with ≥ 105 cfu/mL
CATH: Single specimen with ≥ 105 cfu/mL
Potentially 102 if “in and out” and not biofilm
Should not be treated (unless UTI symptoms)

34. Asymptomatic Bacteriuria
2019 IDSA Guidelines
Screening for or treatment of asymptomatic bacteriuria is not recommended for the following persons.
Healthy, non-pregnant women
Pediatrics
Older persons living in the community
Older persons in LTCFs
Diabetic men and women
Solid organ (including renal) transplant
Spinal cord injury
Indwelling urinary catheter
Non-urologic surgery

35. Determination of UTI 2019 Guidelines – No help with biomarkers
McGeer Criteria for NH residents (developed 1991)
Supported by: Association for Professionals in Infection Control (APIC) and the Society for Healthcare Epidemiology of America (SHEA)
Also supported by CMS and DHHS
30% sensitive, 82% specific
Loeb Criteria for NH residents (developed 2001)
No “official” support
19% sensitive, 89% specific

36. Determination of UTI No Catheter Yes Catheter McGeer Criteria
3 Must Be Present
Yes Catheter
2 Must Be Present
Fever > 100 F or chills
New or increased burning w/urine
New flank pain
Changes to urine properties
Mental function decline

37. Determination of UTI Loeb Criteria
Must have fever > 100 F or > 2.4 F above baseline AND one of the following (new or worsening):
Urgency
Frequency
Suprapubic pain
Gross hematuria
Costovertebral angle tenderness
Urinary incontinence

38. Cortes-Penfield, et al (2017)

39. Urine for a treat (still sorry)
Jamie McCarrell, Pharm.D., BCPS, BCGP