Well Mans Lecture Urinary Incontinence Benign Prostatic Hyperplasia

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Well Mans LectureUrinary Incontinence Benign
Prostatic Hyperplasia

• Crystal Obering, Pharm.D., MBA
• Clinical Assistant Professor
• VA Medical Center
• Kansas City, MO

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Urinary Incontinence
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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence

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Epidemiology of Incontinence

• Involuntary loss of urine that is a social or
  hygienic problem
• Women 15-64 10-30
• Men 15-64 1.5-5
• Women gt 60 yo (ambulatory) 38 report
• Men 9 report
• Prevalence increasing with age
• One of the most common reasons for
  institutionalization
• 50 of LTC residents
• Children ..refer to specialist

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Physiology of Continence

• Motor nervous system
• Both parasympathetic and sympathetic innervate
• Sympathetic
• ß body of bladder (detrusor)
• a base of bladder and proximal urethra
• Activate to hold urine
• Parasympathetic
• Cholinergic throughout bladder
• Activate to release urine
• Sensory nervous system
• External sphincter allows voluntary control

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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence

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Types of Incontinence

• Urge Incontinence
• Stress Incontinence
• Overflow Incontinence
• Obstruction
• Mixed Incontinence
• Stress with urge
• Urge with overflow
• Functional Incontinence

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Symptoms of Stress Incontinence

• Small amounts of urine lost
• Involuntary loss of urine during activities that
  increase abdominal pressure
• Coughing, sneezing, laughing, lifting
• What happens
• Urethral UNDER activity
• Brief pressure exceeds urethral pressure
  resistance and allows leakage of urine

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Symptoms of Urge Incontinence

• Large amounts of urine lost
• Short warning time
• Gotta go!
• What happens
• Bladder OVER activity
• Uninhibited contractions in the absence (detrusor
  instability) or presence of neurologic deficits
  (detrusor hyperreflexia)

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Symptoms of Overflow Incontinence

• Continual leakage of small amounts of urine
• Hesitancy
• Diminished/interrupted stream
• Straining to void
• Sense of incomplete emptying
• What happens
• Urethral OVER activity and/or Bladder UNDER
  activity
• Over-distension of bladder secondary to outlet
  obstruction
• Underactive, acontractile detrusor

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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence

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Case Study

• A 42 year old WF in for routine visit complains
  of urine leakage with coughing and sneezing.
  This first started 3 years ago during her last of
  4 pregnancies, but has gotten worse over the past
  year. Although the amount of urine lost is small
  and controlled with panty liners, she is
  self-conscious about the odor and potential
  visible urine leakage, particularly when standing
  at the chalkboard in front of her 4th grade
  students.

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Diagnosis

• Often under-diagnosed
• Conceal it due to embarrassment
• Ask about
• wearing pads
• Frequency of changing bed
• Voiding diary to access severity
• Assess effect on activities and relationships
• Major presenting symptom(s)
• Differential diagnosis

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Overall Goal in Treating Incontinence

• Minimize signs/symptoms most bothersome to
  patient
• Return patient to normal bladder and UT
  functioning

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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence

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Causes of Incontinence

• Delirium
• Infection
• Atrophic vaginitis
• Pharmaceuticals
• Pregnancy
• Psychological disorders
• Excess fluid intake
• Restricted mobility
• Stool

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Medications that Contribute

• Anticholinergics
• Sedatives
• Loop diuretics
• Adrenergic agents (a and ß)
• ACE Inhibitors
• Calcium channel blockers
• Alcohol
• Caffeine

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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence

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Non-Pharmacologic Treatments

• Bladder retraining
• Scheduled toileting/Prompted voiding
• Pelvic floor exercises (female)
• Biofeedback/electrical stimulation
• H2O Consumption
• Limit caffeine intake
• Absorbent products
• Catheterization
• Surgical

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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence

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Pharmacologic Treatment Goals

• Urge
• ? uninhibited bladder contractions
• Stress
• ? intraurethral pressure
• Overflow
• facilitating bladder emptying and ? residual urine

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Case Study

• The 42 year old patient agrees to implement
  many of the recommended non-pharmacological
  options, but was wondering if there is something
  she can take to help in the interim. As the
  clinical pharmacist in this clinic the physician
  relies on you as his drug information source,
  what would you recommend to him?

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Stress Incontinence

• a1-adrenergic agonists
• Phenylpropanolamine
• Removed 2000 hemorrhagic stroke
• Pseudoephedrine
• Estrogen
• Imipramine

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Choice of Therapy

• Pseudoephedrine
• First line
• 15-30mg TID
• Only agent available on US market
• Estrogen
• Second line agent urethritis or vaginitis
• Only topical estrogen formulations
• 0.5g 3 times week x 8 months
• Somewhat more effective if combined with
  a1-adrenergic agonists

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Contraindications and Side Effects

• Pseudoephedrine
• CARDIAC!!
• Insomnia
• Anxiety
• Headaches
• Estrogen
• Breast cancer
• Endometrial cancer
• Heart disease
• Nausea, vomiting, headache

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Case Study

• The 42 year old patient agrees to implement
  many of the recommended non-pharmacological
  options, but was wondering if there is something
  she can take to help in the interim. As the
  clinical pharmacist in this clinic the physician
  relies on you as his drug information source,
  what would you recommend to him?

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Case Study

• A 78 year old female, accompanied by her
  daughter, returns for a routine visit after being
  discharged from a 3-mo inpatient stroke
  rehabilitation program. She has some residual
  weakness in her left lower extremity that
  requires her to have assistance with many ADLs.
  Since the stroke she has also experienced urgency
  and associated urinary incontinence. This
  unexpected loss of urine is embarrassing and her
  daughter feels it adds burden to caregiving.

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Urge Incontinence

• Anticholinergic/antispasmodic drugs
• Non-selective M antagonist
• Oxybutynin (Ditropan)
• Immediate release
• Extended release
• Patch
• Tolterodine (Detrol)
• Extended release
• Immediate release

• M3/M1 antagonist
• Trospium (Sanctura)
• M3 antagoinist
• Solifenacin (Vesicare)
• Darifenacin (Eneblex)
• Propantheline

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Urge Incontinence

• Other agents
• TCAs
• Dicyclomine
• Estrogen

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Anticholinergic/Antispasmodic Drugs

• First line drug therapy
• Oxybutynin or tolterodine preferred
• Site of action
• Oxybutynin
• Muscarinic blocker M3gtM2
• Histamine1-receptor blocker
• a1-receptor blocker
• Tolterodine
• Muscarinic blocker M2gtM3
• Trospium
• Muscarinic M3/M1 blocker
• Solifenacin/Darifenacin
• Muscarinic M3 blocker

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Anticholinergic/Antispasmodic Dosing

• Oxybutynin IR
• Starting 2mg BID
• Maximum 5mg QID
• Oxybutynin XL
• Starting 5mg QD
• Maximum 30mg QD
• Oxybutynin TD Patch
• 39 cm2 patch 2 x /week (3.9mg/day)

• Tolterodine IR
• Start 1mg BID
• Maximum 2mg BID
• Toterodine LA
• Start 2mg QD
• Maximum 4mg QD

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Anticholinergic/Antispasmodic Dosing

• Trospium
• Start 20mg BID
• Elderly 20mg QHS

• Sulifenacin
• Start 5mg qday
• Max 10mg qday
• Elderly 5mg qday
• Darifenacin
• Start 7.5mg qday
• Max 15mg qday
• Elderly 7.5mg qday

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Dosing Adjustments Maximum Doses

• Darifenacin
• Hepatic Impairment/ potent 3A4 7.5mg/day
• Oxybutynin
• Start at lowest dose and increase by 5 mg / week
• Solifenacin
• Hepatic/Renal Impairment/Potent 3A4 5mg/day
• Tolterodine
• Hepatic/Renal Impairment or potent 3A4
• IR 1mg BID
• ER 2mg Qday
• Trospium
• Renal Impairment Max dose 20mg qhs
• gt75 yo titrated down to 20mg qday

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Anticholinergic/Antispasmodic Dosing

• Takes 8-10 weeks to see clinical improvement
• Modest improvement seen
• All PO formulations are equally effective
• Extended release formulations produce fewer side
  effects, are better tolerated
• TD cause less ACh side effects, less effective,
  and more skin irritation than PO formulations
• Trospium absorption is significantly affected by
  food

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Anticholinergic/Antispasmodic Side Effects

• Anticholinergic
• Anti-SLUDGE
• Confusion
• Sedation
• Worsening narrow angle glaucoma
• Tachycardia
• Dyspepsia
• Worsening of incontinence

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Anticholinergic/Antispasmodic Interactions

• Digoxin
• Procainamide
• Morphine
• Metformin
• 3A4 Inhibitors

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Other Urge Incontinence Therapies

• TCAs
• Limited to nocturnal incontinence refractory to
  other therapies
• Those with additional medical indications (e.g.
  neuropathy, depression)
• Dicyclomine
• Lacks sufficient evidence for use
• Topical Estrogen
• Limited to atrophic vaginitis and urethritis

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Case Study

• A 78 year old female, accompanied by her
  daughter, returns for a routine visit after being
  discharged from a 3-mo inpatient stroke
  rehabilitation program. She has some residual
  weakness in her left lower extremity that
  requires her to have assistance with many ADLs.
  Since the stroke she has also experienced urgency
  and associated urinary incontinence. This
  unexpected loss of urine is embarrassing and her
  daughter feels it adds burden to caregiving.

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Overflow Incontinence

• Medication induced
• Women
• Generally managed by non-pharmacological
  procedures
• Small sub-group with prostatism-like symptoms
• Men
• Primary cause is BPH

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Benign Prostatic Hyperplasia
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BPH Objectives

• Discuss the epidemiology and pathophysiology of
  benign prostatic hyperplasia (BPH)
• Discuss the diagnosis of BPH
• Compare the pharmacologic treatment strategies
  for BPH
• Describe the non-pharmacologic options for BPH

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Epidemiology of BPH

• Risk factors
• Age gt 40 years old, rarely occurs before age 50
• Normal testicular function not seen if castrated
  before puberty
• 80 develop microscopic changes characteristic of
  BPH by age 80
• 50 develop symptomatic BPH

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The Prostate Gland

• Healthy Adult Male
• Soft
• Nontender
• Symmetrical
• Mobile/Elastic
• 4-20 g
• No nodules
• PSA0-4

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Etiology of BPH

• Second prostate growth spurt at age 40 until age
  80-90
• Can grow to 50-80 g or larger
• Dihydrotestosterone (DHT) and 5-a reductase
  levels constant in stromal tissues vs. decline in
  epithelial tissue

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Hyperplasia vs. Hypertrophy

• Hyperplasia
• Increased number of cells
• Hypertrophy
• Cells get larger

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Pathophysiology of BPH

• Static Factors
• Related to enlargement of prostate gland
• Requires presence of DHT
• Blocks bladder neck and obstructs urinary flow
• Dynamic Factors
• Related to smooth muscle tone of prostate gland
• Related to a-adrenergic tone of prostate
• Contracts around urethra and obstructs urinary
  flow

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BPH Objectives

• Discuss the epidemiology and pathophysiology of
  benign prostatic hyperplasia (BPH)
• Discuss the diagnosis of BPH
• Compare the pharmacologic treatment strategies
  for BPH
• Describe the non-pharmacologic options for BPH

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Case Study

• A 52 year old WM presents to the clinic with
  complaints of urinary hesitancy and nocturia. He
  is also complaining of his seasonal allergies,
  but has been able to control these during the
  daytime with diphenhydramine 25mg q 6 hrs prn.

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Clinical Symptoms

• Obstructive (early)
• Force of urine stream
• Hesitancy
• Abdominal straining on urination
• Terminal dribbling
• Incomplete emptying
• Intermittency

• Irritative (late)
• Nocturia
• Frequency of urination
• Urgency
• Dysuria
• Urge incontinence

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Diagnosis

• Medical Exam
• Hematuria, UTI, DM, CNS, urinary retention
• Medication History
• Physical Exam
• Digital rectal exam (DRE) size, shape,
  consistency, nodularity
• Postvoid residual urine volume
• Pressure flow studies

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Diagnosis

• Symptom-based patient self-assessment
• American Urological Association (0-35 pts)
• 0-7 Mildly symptomatic
• 8-19 Moderately symptomatic
• 20-35 Severely symptomatic
• Objective measures
• Lab tests UA, SCr, PSA
• Post-void residual urine, peak flow rate,
  pressure flow study
• Differential diagnosis

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Diagnostic Tests

• Post-void residual urine
• Ultra sound
• Catheter into bladder and volume of urine
  obtained measured
• Normal 12-28mL
• Usually gt200mL in incontinent pts

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Diagnostic Tests

• Peak flow urine rates
• Measures how fast urine is passed
• Pressure flow study
• Urodynamic catheter in bladder
• Allows measurement of pressure and urine flow
  during voiding

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Goal for BPH Treatment

• Reduce symptoms of BPH
• Decrease bladder outlet obstruction
• Decrease residual urine volume
• Reduce incidence of urinary retention and renal
  insufficiency
• Improve QOL

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BPH Objectives

• Discuss the epidemiology and pathophysiology of
  benign prostatic hyperplasia (BPH)
• Discuss the diagnosis of BPH
• Describe the non-pharmacologic options for BPH
• Compare the pharmacologic treatment strategies
  for BPH

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Treatment Options

• Patient ultimate decision
• Watchful waiting
• Surgical
• Pharmacological

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Watchful Waiting

• Option for mild to moderate symptoms (AUA lt7)
• If symptoms progress/worsen, drug treatment
  should be considered
• Counsel patient on
• Medications that worsen symptoms
• Behavior modifications
• Medications

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Medications that Worsen Symptoms

• a-Adrenergic agonists
• Cold remedies topical and oral
• Anticholinergics
• Antihistamines
• TCA
• Antispasmodics
• PD therapies
• Testoterone replacement
• Diuretics

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Behavior Modifications

• Late day/evening water consumption
• Limit alcohol intake
• Limit coffee or other caffeine containing products

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Surgical Intervention

• Transurethral resection of the prostate (TURP)
• Transurethral incision of the prostate (TUIP)
• Open prostatectomy
• Risk of impotence and incontinence

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BPH Objectives

• Discuss the epidemiology and pathophysiology of
  benign prostatic hyperplasia (BPH)
• Discuss the diagnosis of BPH
• Describe the non-pharmacologic options for BPH
• Compare the pharmacologic treatment strategies
  for BPH

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Case Study

• After a short discussion, he decides to try
  behavior modifications and use of a NS for
  allergies. 6 months pass. He returns to clinic
  reporting increased difficulty initiating and
  maintaining a stream of urine. He also reports
  having to extensively use his abdominal muscles
  to help him empty more completely. AUA score 12.
• PE PVR 500cc
• PSA 3.0
• DRE enlarged, firm, rubbery

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Pharmacologic Treatment for BPH

• a-Adrenergic antagonists
• 5-a Reductase inhibitors

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a-Adrenergic Antagonists

• Dynamic component
• Relaxation of musculature of prostatic stroma,
  capsule, and bladder neck
• 1st Generation
• Unacceptable SE, not recommended
• Selective to 1a receptors of prostate
• 2nd Generation
• Doxazosin
• Terazosin
• 3rd Generation
• Tamsulosin
• Alfuzosin

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Dosing a-Adrenergic Antagonists

• 2nd Generation
• Start low, titrate up
• Initial doses
• Terazosin/Doxazosin 1mg QHS
• Benefits seen after titration of dose (2-4 wks)
• Terazosin 4mg QHS
• Doxazosin 5mg QHS
• 3rd Generation
• Tamsulosin 0.4mg QHS
• Afluzosin 10mg QHS
• No titration needed

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a-Adrenergic Antagonists Side Effects

• Hypotension
• Syncope
• Weakness
• Nausea/Vomiting

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a-Adrenergic Antagonists Drug-Drug Interactions

• Other Blood pressure lowering medications

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a-Adrenergic Antagonists Monitoring

• PSA
• BP
• Resolution of BPH symptoms (AUA symptom index)
• Can take 4-6 weeks to see improvement
• ALLHAT concerns

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Case Study

• The next patient you see in urology clinic is a
  75 year old male. He has been on tamsulosin
  0.8mg QHS for 3 years and is reporting worsening
  over the past year of his target symptoms,
  particularly increased nocturia (4-6 times) and
  the sensation of always needing to urinate but
  many times not able to produce any urine.
• PE DRE 65g, soft, and smooth
• PSA 5.0
• Glucose 120

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5-a Reductase Inhibitors

• Static component
• Decrease size of prostate gland
• Finasteride
• Dutasteride
• Type 1 isoenzyme 5-a Reductase inhibitor (70)
• Similar clinical effectiveness
• Delayed onset of improvement (6 mo)
• More useful in larger prostate size

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5-a Reductase Inhibitors Side Effects

• Sexual dysfunction
• Breast enlargement
• Rash
• ? Breast cancer
• ? Bone fractures
• Category X finasteride
• No significant drug-drug interactions

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5-a Reductase Inhibitors Monitoring

• PSA serum values doubled to compare to baseline
  for possibility of cancer
• BPH symptoms (AUA symptom index)
• Side effects

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Combination Therapy

• a-Adrenergic antagonists and 5-a reductase
  inhibitors
• Prostate Size 50 g
• Relief of dynamic symptoms
• Long-term benefits of 5-a reductase inhibitors
• Decreased need for surgical intervention

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Alternative therapies

• Saw Palmetto
• Improvement of urinary symptoms
• Similar to results with finasteride
• Increased sexual dysfunction with Saw Palmetto
• Consistency of product
• Small uncontrolled studies
• Alternative if no response to pharmacologic agents

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BPH Follow Up

• Effect seen after initiation of.
• a-Adrenergic antagonist 4-6 weeks
• 5- Reductase inhibitor 4-6 months
• Routine Labs
• AUA symptom index
• Baseline, q 3 mo, Q 6 mo
• UA, PCr
• Baseline, Q 6 mo
• PSA, DRE
• Baseline, Q 6 mo, annual
• Pressure flow, residual urine volume
• Baseline, Q 6 mo PRN

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BPH Objectives

• Discuss the epidemiology and pathophysiology of
  benign prostatic hyperplasia (BPH)
• Discuss the diagnosis of BPH
• Describe the non-pharmacologic options for BPH
• Compare the pharmacologic treatment strategies
  for BPH

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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence

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Mixed Incontinence

• Choice of therapy
• Depends on predominate symptoms and etiology

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Future Therapies

• Stress Incontinence
• 5-HT and NE reuptake inhibitors in urethral
  sphincter
• Duloxetine (Yentreve)
• Benign Prostatic Hyperplasia
• Sildosin
• Ionidamine

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Urinary Incontinence Therapy Monitoring

• Resolution of symptoms
• Appearance of side effects
• Adherence to medication and non-pharmacologic
  interventions
• Development of contraindications

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Urinary Incontinence Objectives

• Discuss the epidemiology of incontinence and
  physiology of continence
• Describe the different types of incontinence and
  associated symptoms
• Understand the diagnosis of urinary incontinence
• Identify causes/aggravating factors of
  incontinence (including medications)
• Describe the non-pharmacologic treatment options
  for incontinence
• Discuss the pharmacologic treatment strategies
  for the different types of incontinence