Treatment of Urinary Incontinence Flashcards
Urinary Incontinence
- Involuntary loss of urine at inappropriate times and places
- Involuntary loss of urine to a degree sufficient to be a problem
Detrusor
- Muscular layer of the bladder
- Parasympathetic cholinergic receptors
- Stimulation by acetylcholine causes detrusor CONTRACTION
- Beta-3 stimulation causes RELAXATION
Internal sphincter
- Located at bladder base at the proximal end of the urethra
- Alpha adrenergic receptors
- Stimulation causes CONTRACTION (closing) of the bladder outlet
- Sympathetic nervous system
External sphincter
- Located at the distal end of the urethra
- Composed of striated muscle, under VOLUNTARY CONTROL
- Somatic nervous system
What are the risk factors for urinary incontinence?
- Immobility
- Impaired cognition/delirium
- Medications
- Morbid obesity
- Smoking
- Environmental barriers
- High-impact physical activities
- Diabetes (polyuria could increase risk of having UI)
- Stroke
- Estrogen depletion
- Pelvic muscle weakness
- Pregnancy
What are the causes of transient/iatrogenic urinary incontinence?
- D = Delirium
- I = Infection
- A = Atrophic vaginitis/urethritis (after menopause)
- P = Pharmaceuticals
- P = Psychological dysfunction
- E = Endocrine (hypercalcemia the body tries to get rid of calcium [polyuria])
- R = Restricted mobility
- S = Stool impaction
What drug category causes sensory issues in urinary incontinence?
CNS acting drugs
(ex: Benzos–> being confused and not being able to interpret cues to avoid)
What drug category causes polyuria?
- Diuretics
- Lithium
What drug categories INCREASES bladder contractility (of the detrusor muscles)?
- Beta blockers
- Cholinergic
What drug categories DECREASE outlet resistance (of internal sphincter)?
Alpha blockers
What drug categories DECREASE bladder contractility (of the detrusor muscle)?
- Anticholinergics
- Beta agonist
- NSAID
- Calcium channel blockers
What drug categories INCREASE outlet resistance (of the internal sphincter)?
- Alpha agonist
- Narcotic analgesics
- Estrogens
What is the first line for the treatment of urinary incontinence?
- Non-surgical, non-pharmacological intervention
- Bladder diary
- Scheduled voiding
- Pelvic floor exercises
- Caffeine and alcohol reduction
- Weight loss
- Fluid management
What is the third line of treatment of urinary incontinence?
- Intradetrusor onabotulinumtoxin A
- Peripheral tibial nerve stimulation
- Sacral neuromodulation
What is the 4th line of treatment of urinary incontinence?
- Augmentation cystoplasty
- Urinary diversion
What are some non-pharmacologic options?
- Bladder-retraining
- Catheterization
- “Kegel” exercises–> pelvic floor exercises
- Surgery
- Hygiene
- Undergarments and shields
What are some therapies/devices that could be used in treatment?
- Device to support the bladder neck (pessary)
- Urethral occlusive devices (plugs or shields)
- External collection systems (condom caths)
- Catheterization (indwelling, intermittent, suprapubic)
- Surgical treatment
What are the different types of incontinence?
- Functional
- Urge
- Stress
- Overflow
- Mixed
What is functional incontinence?
Involuntary loss of urine due to inability to use toilet or toilet substitute
What are the causes of involuntary incontinence?
- Physical–> broken hip
- Cognitive–> advanced dementia
- Environmental factors–> bathroom location
- Limited mobility (common cause)
- Change in mental status (common cause)
What are the treatments of involuntary incontinence?
- Eliminate causes
- Scheduled voiding
- Assistive devices
- Behavioral therapy
- Undergarments, pads
- External collection devices
What are some complications from absorbent products?
- Skin irritation and maceration
- Urine odor
How do you treat skin irritation and maceration from absorbent products?
- Change every 2-4 hours
- Use skin protectants (barrier creams and ointments)
- Pressure ulcers–need to contact PCP
How do you mitigate urine odor from absorbent?
Nonprescription chlorophyll tablets (Derifil, Pals, Nullo), available but rarely used
What is urge urinary incontinence (UUI)
- Inability to delay voiding
- Sudden loss of moderate to large amounts of urine, usually accompanies with a strong desire to void, known as urgency
What is the treatment of urge urinary incontinence?
- Behavioral therapy
- Pharmacological options
Anticholinergic/antispasmodics
- DOC
- MOA: Antagonize muscarinic cholinergic receptors
What are the side effects of immediate-release oxybutynin?
- Dry mouth cited as major reason patients discontinue therapy
- Constipation
- Vision impairment
- Confusion
- Tachycardia
- Orthostatic hypotension
However no clinically relevant DDIs
Transdermal Oxybutynin
- Apply twice weekly; every 3-4 days
- Apply to abdomen, hip, or buttock area that is clean and dry
- Bypasses first pass metabolism (less side effects)
What are the side effects of transdermal oxybutynin?
Most common:
* Pruritis
* Erythema at the application site
- Dry mouth, constipation, dizziness (occur less freqeuntly than IR)
Oxybutynin chloride 10% gel
- Apply contents of one sachet once daily to dry, intact skin on the abdomen, upper arms/shoulders or thighs
- Rotate application sites, avoid use of same site on consecutive days
What are some patient counseling points of Oxybutynin chloride 10% gel?
- Should NOT be applied to recently shaved skin
- Avoid smoking until gel has dried (EtOH based)
- Wash hands IMMEDIATELY after application
- To avoid potential transfer to another person, cover application site with clothing after gel has dried if skin-to-skin contact is anticipated
- Can apply sunscreen 30 min before or after application
- Showering 1 hour after application does NOT affect absorption
Tolterodine (Detrol, Detrol LA)
- MOA: Acts by muscarinic receptor blockade in the bladder wall and detrusor muscle
- Can be considered as first line therapy
What is the metabolism of tolterodine (Detrol, Detrol LA)?
- Extensive first pass hepatic metabolism
- Polymorphic metabolism:
- Extensive metabolizers primary pathway involves the cytochrome 2D6 isozyme
- Poor metabolizers primary pathway involves the cytochrome 3A4 isozyme (elimination may be inhibited by fluoxetine, macrolides, azoles, and grapefruit juice)
What are the some patient counseling points of tolterodine (Detrol, Detrol LA)?
- Recommened dose 1 mg BID (IR) or 2 mg (LA) QD for patients with REDUCED hepatic function and those receiving CYP3A4 and CYP2D6 inhibiting drugs
- No renal dosage adjustment
- LA product should be taken less than 2 hours before or 4 hours after antacid administration
What is the side effects of tolterodine (Detrol, Detrol LA)?
- Dry mouth
- Dyspepsia
- Headache
- Constipation
- Dry eyes
What are side effects of Imipramine (Tofranil)?
- Above plus ortho hypotension and EKG effects
- Reserved for patients with additional indication (depression)
Trospium chloride (Sanctura)
- Poorly absorbed
- Food reduces bioavailability by 70-80%
- Cleared renally
- Dose reduction to 50% if CrCl < 30 ml/min
What is the patient counseling points of Trospium Chloride (Sanctura)?
- Expected anticholinergic effects
- Increased in patients > 75 yo, so reduce frequency to daily instead of BID
- Administer 1 hour BEFORE meals or on an empty stomach
Solifenacin succinate (Vesicare)
- An antagnoist at M1, M2, and M3 muscarinic cholinergic receptors
- “Uroselective”
- If ECrCl < 30 ml/min or moderate hepatic impairment–> should NOT exceed 5 mg
- Do NOT use in severe hepatic impairment
- Do NOT exceed 5 mg if coadministered with potent CYP3A4 inhibitors
What are the side effects of Solifenacin succinate (Vesicare)?
- Dry mouth
- Constipation
- Blurred vision
- Similar extent as tolterodine and oxybutynin
Darifenacin ER (Enablex)
- An antagnoist at M1, M2, and M3 muscarinic cholinergic receptors
- Extensively metabolized by 2D6 and 3A4
What are the side effects of Darifenacine ER (Enablex)?
- Dry mouth
- Constipation
- And other anticholinergic effects
What are the side effects of Fesoterodine fumarate (Toviaz)?
- Dry mouth
- Constipation
Fesoterodine fumarate (Toviaz)
Starting dose is 4 mg once daily and could be increased to 8 mg except for severe renal insufficiency (ECrCl < 30 ml/min) and patients taking potent CYP3A4 inhibitors such as ketoconazole, itraconazole, and clarithromycin
What are the anticholinergic/antispasmodics?
- Oxybutynin
- Tolterodine
- Imipramine
- Trospium chloride
- Solifenacin
- Darifenacin ER
- Festerodine fumarate
What is the MOA of Mirabegron (Myrbetriq)?
Activates beta-3 adrenergic receptors in bladder
What are the side effects of Mirabegron (Myrbetriq)?
- Elevations in BP
- Nasopharyngitis
- UTI
- Constipation
- Fatigue
- Tachycardia
- Abdominal pain
What are some patient counseling points in Mirabegron (Myrbetriq)?
-Because of its hypertensive properties, mirabegron should NOT be used in patients with severe uncontrolled hypertension (systolic blood pressure of 180 mmHg or more and/or diastolic blood pressure of 110 mmHg or more)
-A moderate cytochrome P450 (CYP)2D6 inhibitor, may interact with drugs that are CYP2D6 substrates
* Dosage adjustments of drugs are metabolized by this enzyme may be needed
-NEED PERIODIC MONITORING OF BP
-Can be used for Alzheimer’s patients
-Some cardiovascular protective properties (not proven)
What is the MOA of Vibegron (Gemtesa)?
Activates beta-3 adrenergic receptors in bladder
What are the side effects of Vibegron (Gemtesa)?
- Headache
- UTI
- Nasopharyngitis
- Diarrhea
- Nausea
- URTI
Post-void residual urinary incontinence
- Normal–> < 50 mL
- If no post-void residual—> urge incontinence
- Anticholinergics is the best treatment
Stress Urinary Incontinence
- SMALL amount of urine loss upon coughing, sneezing, laughing, straining (due to INCREASED intraabdominal pressure)
- Weakness of sphincter and pelvic floor muscles
- Urethral hypermobility
What is the treatment of stress urinary incontinence (SUI)?
- Pelvic floor exercises (Kegel)
- Behavioral therapy
- Devices (Pessaries)
- Pharmacological options
Estrogen (topical)
- For peri – or postmenopausal women with vaginal atrophy due to genitourinary syndrome of menopause (GSM)
- Pharmacological option for stress urinary incontinence (NOT FDA approved)
What is the MOA of estrogens (topical)?
Enhancement of urethral epithelium, local circulation, and numbers and/or sensitivity of urogenital alpha-adrenergic receptors in sphincter
Duloxetine (Cymbalta)
- Dual inhibitor of serotonin and norepinephrine reuptake
- Serotoninergic and noradrenergic regions are involved in control of urethral smooth muscle and in the external urethral sphincter
- Used in Europe, NOT US FDA APPROVED for stress urinary incontinence
What are the side effects of Duloxetine (Cymbalta)?
- Nausea (up to 46%)
- HA
- Insomnia
- Constipation
- Dry mouth
- Small increase in BP
- Withdrawal symptoms (sleep disturbances)
- If drug is to be stopped, it should be reduced by 50% for two weeks before d/c
Alpha-agonist
- Use of nonprescription medications for incontinence is considered an off-label indications and should be prescribed by a physician
- MOA: Affect urethral closure pressure and functional urethral length
- No longer recommended because they are only MILDLY efficacious and have a high rate of AEs
What are the side effects of Pseudo-ephedrine (Sudafed)?
- HTN
- HA (increased BP)
- Dry mouth
- Nausea
- Anxiety
- Insomnia
- Restlessness
What are some contraindications of alpha agonist?
- HTN
- Tachyarrhythmias
- CAD
- MI
- Coronary pulmonale
Overflow Incontinence (OFI)
- Constant loss of SMALL volume of urine
- Large volume of residual urine
- Large, distended bladder
- Symptoms include dribbling, sense of incomplete voiding, reduced force of stream, and urgency
What are the treatments for Overflow incontinence (OFI)?
- Relieve obstruction
- Intermittent catherization
- Pharmacologic options:
- Alpha-1 adrenergic antagonist
- Cholinergic agents (rarely used)
What are some side effects of alpha-1 adrenergic antagonist?
- Dizziness
- Syncope
- Orthostatic hypotension
- HA
- CNS effects
