Term
|
Definition
the involuntary loss of urine severe enough to have social and/or hygienic consequences - not a disease, but a symptoms with many causes
10 million Americans suffer from UI
15-35% of community dwelling elderly and 50+% of nursing home residents suffer from UI
costs conservatively $16 billion annually
UI is NOT a normal consequence of aging
UI is underdiagnosed due to patient reluctance to report
prevalence rates are twice as high in women as in men |
|
|
Term
| risk factors for UI (not well defined) |
|
Definition
immobility
gender
parity
UTIs
menopause
GU surgery
lack of postpartum exercise
various medications
**NOT CHRONIC BACTERIURIA OR AGE** |
|
|
Term
| clinical, psychological, and social impact |
|
Definition
rashes
pressure sores
skin and urinary tract infections
odor
restriction of activity
embarrassment, isolation, depressive symptoms
sexual dysfunction
instituionalization |
|
|
Term
|
Definition
lower urinary tract is a high volume, low pressure system
intravesicular pressure = bladder volume
intraabdominal pressure
detrusor tone
intraurethral pressure
to maintain continence, intraurethral pressure must exceed intravesicular pressure |
|
|
Term
|
Definition
dysfunction of the bladder outlet (urethral sphincter weakness) leading to transient loss of small amounts of urine when intra-abdominal pressure increases
coughing, laughing, sneezing, bending, lifting
posterior urethrovesicular angle changes (parity, surgery)
strength or responsiveness of urethral sphincter
patients often dry at night |
|
|
Term
| detrusor instability/overactive bladder (OAB) and urge incontinence |
|
Definition
most common type (70%); unstable bladder, spastic bladder
CNS dysregulation, stroke, PD, AD, neoplasm, NPH
hyperreflexia of afferent pathways
deconditioned voiding reflexes
clinical features: urgency, frequency, nocturia, frequent small volume voiding
no characteristic features on physical exam, although CNS dysfunction may be apparent |
|
|
Term
|
Definition
occurs when intravesicular pressures exceed intraurethral pressures - ONLY at HIGH volumes
bladder outlet obstruction - BPH, neoplasm
impaired afferent sensation
diabetic neuropathy (bladder doesn't empty completely), spinal cord lesions below T-11
muscle relaxants, calcium channel blockers, anticholinergics
clinical features: palpable or percussable bladder, suprapubic tenderness, lower urinary flow rates, post-void residual urine |
|
|
Term
|
Definition
the inability of a normally continent person to reach the toilet in time to avoid an accident
musculoskeletal limitation - joint pain, arthritis, muscle weakness
unfamiliar setting, lack of conventional toilet facilities
clinical features: accidents on the way to the toilet and early morning incontinence are suggestive of this type |
|
|
Term
|
Definition
may aggravate or unmask above causes
potent fast acting diuretics - lasix
sedative hypnotics, neuroleptics
muscle relaxants
alpha1 agonists - PPA, pseudoephedrine
pinch the urethra bladder neck = overflow incontinence
alpha1 antagonists - terazosin, prazosin
in females relax the urethra sphincter; beneficial in males with BPH
anticholinergics
parasympathetic innervation = contraction of bladder
parasympathetic antagonism = relaxation of bladder
calcium channel blockers |
|
|
Term
| UI evaluation and diagnosis |
|
Definition
medial history/labs/urodynamics
urinary complaints (frequency, low flow)
MMSE, depression screening
glucose, urinalysis, urine culture
post void residual (PVR)
cystometry
volume at first contraction
maximal cystometric capacity
urinary flow measurement
urethral pressure profile
imaging studies - IVP (intravenous pyelogram) to look for physical barriers |
|
|
Term
|
Definition
amount of urine remaining in the bladder following attempt by the patient to empty the bladder
normal < 50 mL
increased > 50 mL
KNOW THE CUTOFFS
assessed by straight catheter placement post void or estimated with bladder scanner |
|
|
Term
|
Definition
abdominal, pelvic, rectal, neurological
rectal exam to rule out fecal impaction, BPH
pelvic exam - atrophic vaginitis
neurological damage (upper motor neurons)
abdominal tenderness (overflow incontinence) |
|
|
Term
| goals of urinary incontinence management |
|
Definition
goals should be individualized based on underlying disease states and disabilities
reduce wetting episodes
improve ADLs and QOL
reduce complications such as falls, pressure ulcers, and pharmacologic ADRs
reduce caregiver burden
reduce cost of direct and indirect continence care
cure or diminish UI and its symptoms, including physical discomfort from UI or comorbid conditions |
|
|
Term
| UI non pharmacologic treatments |
|
Definition
scheduling regiments/timed voiding
prompted voiding
bladder training
pelvic floor exercise/Kegel exercises
vaginal weight training
biofeedback
pessaries/bladder neck support prostheses
[image]
NOTE: you will achieve MUCH better results controlling incontinence symptoms when behavioral interventions are used in combination with medication therapies. medications alone have been shown to be of minor benefit when used alone, especially in patients in nursing home settings
CAUTION: any drug used to treat incontinence can make it worse if the diagnosis is wrong or the patient has more than 1 type of incontinence |
|
|
Term
| treatment of stress incontinence |
|
Definition
aim: increase resistance to sudden increases in intra-abdominal pressure
Kegal exercises
topical estrogens for atrophic vaginitis
pseudoephedrine 15 to 60 mg TID
pinches the neck of the bladder
ADR: dizziness, increased BP, insomnia, HA
contraindications: HTN, arrhythmias, MI/CAD, hyperthyroidism
duloxetine (Cymbalta) - dual inhibitor of serotonin and NE
FDA approved in 2004 for depression and diabetic neuropathy
not FDA approved for stress incontinence
40-80 mg/day in 1-2 doses has been shown to improve symptoms of stress incontinence in several studies
ADRs: HA, insomnia, constipation, dry mouth, dizziness, fatigue, increased BP
reserved for patients with other underlying conditions (concurrent depression or neuropathy) |
|
|
Term
| treatment of overflow incontinence |
|
Definition
aim: to improve complete bladder drainage
prazosin 1-5 mg BID to TID
terazosin 1-10 mg HS
doxazosin 1-8 mg HS
phenoxybenzamine 10 mg QD-TID
ADRs: hypotension, tachycardia, impotence
bethanechol 10 mg TID
ADRs: diarrhea, flushing, cramping
cholinergic agonist = contraction of the bladder
used for a patient with atonic bladder (long standing diabetes)
5 alpha reductase inhibitors (finasteride, dutasteride) |
|
|
Term
| acute urinary retention (AUR) |
|
Definition
painful
initial management by catheterization (often in ER setting)
refractory urinary retention may require surgical intervention |
|
|
Term
| American Urological Association - Symptom Index (AUA-SI) |
|
Definition
scale: 0 (not at all) to 5 (almost always)
symptoms:
incomplete emptying
frequency
intermittency
urgency
weak stream
straining
nocturia |
|
|
Term
|
Definition
TERAZOSIN (HYTRIN)
MOA: long acting alpha1 blocker
t1/2 = 12 hours
time to onset: days to weeks
recommended HS
non selective, will also lower BP
titration required
possible interactions with PDE5 inhibitors
DOXAZOSIN (CARDURA)
MOA: long acting alpha1 blocker
t1/2 = 22 hours
time to onset: days to weeks
non selective, will also lower BP
titration required
possible interactions with PDE5 inhibitors
TAMSULOSIN (FLOMAX)
MOA: long acting alpha1a blocker
t1/2 = 9-15 hours
time to onset: days
recommended ~30 minutes after same meal each day
selective - relaxes the urethra and prostate tissue, but does NOT lower BP
titration may or may not be required
possible interactions with PDE5 inhibitors
ALFUZOSIN (UROXATRAL)
MOA: long acting alpha1 blocker
t1/2 = 9 hours
time to onset: days
recommended with same meal each day
titration not required
should not be administered with potent 3A4 inhibitors (ketoconazole)
possible interactions with PDE5 inhibitors
SILODOSIN (RAPAFLO)
MOA: long acting alpha1a blocker
t1/2 = 13.5 hours
time to onset: days
recommended with same meal each day
selective - relaxes the urethra and prostate tissue, but does NOT lower BP
titration not required
possible interactions with PDE5 inhibitors
inhibitors of 3A4 and Pgp increase exposure
according to the AUA guidelines, the alpha blockers are "similarly effective"; however the ADRs appear slightly different |
|
|
Term
| treatment of detrusor instability (OAB) |
|
Definition
aim: eliminate or reduce uninhibited detrusor contractions
anticholinergics:
decrease detrusor contractions
increase bldder capacity
decrease symptoms of urgency
ADRs such as dry mouth, constipation, cognitive impairment are common
study variables: urgency episodes, incontinence episodes, volume voided, volume at first contraction, maximal cystometric capacity
efficacy is similar between agents, difference is with the ADRs of the different anticholinergics
M3 and M2 muscarinic receptors predominate in the bladder
M3 is responsible for the contractions (stimulate M3 = contraction)
stimulate M2 = relax the bladder
enablex and vesicare are considered M3 selective drugs; the predominant effect of these drugs are on the bladder (cause less constipation, dry mouth, and cognitive impairments)
oxybutynin (Ditropan) 2.5-5 mg BID-TID
oxybutynin XL (Ditropan XL) 5-30 mg QD
oxybutynin patch (Oxytrol) 3.9 mg 2x/week
doesn't have as many ADRs as the PO form
tolterodine (Detrol) 1-2 mg BID
metabolized by 2D6 to the active form (a portion of the population are 2D6 poor metabolizers)
tolterodine LA (Detrol LA) 2-4 mg QD
trospium chloride (Sactura) 20 mg QD-BID
solifenacin (Vesicare) 5-10 mg QD
darifenacin (Enablex) 7.5-15 mg QD
fesoterodine (Toviaz) 4-8 mg QD
prodrug that is metabolized outside the 2D6 system (serine esterases instead) |
|
|
Term
treatment of detrusor instability (OAB):
oxybutynin |
|
Definition
oral administration - DEO metabolite
DEO thought to be related to ADRs
DEO highest with oxybutynin IR
60-80% dry mouth
DEO lowest with oxybutynin patch/gel
10-15% dry mouth
bypass first pass metabolism
TRANSDERMAL OXYBUTYNIN
patch (matrix) - drug is mixed into the adhesive layer
dose delivery rate is 3.9 mg oxybutnin per day
patch placed on skin, drug passes through skin into bloodstream (bypass first pass metabolism)
administer 1 patch every 3-4 days
replaceing the patch the same 2 days each week (Sunday and Wednesday) may improve compliance
rotate application to abdomen, hip, or bottock
bathing should not affect adhesion
new oxybutynin gel product FDA approved (Gelnique) |
|
|
Term
treatment of detrusor instability (OAB):
tolterodine |
|
Definition
metabolized via 2D6 to active substance 5 hydroxy methyl tolterodine (5-HMT)
poor metabolizers may have poor response to tolterodine |
|
|
Term
treatment of detrusor instability (OAB):
Sanctura (trospium chloride) |
|
Definition
MOA: antimuscarinic
indication: OAB (urgency, frequency, UUI)
20 mg BID (20 mg QD is CrCl < 30 ml/min)
ADME:
<10% absorbed - empty stomach/1 hour before meals
mainly non-CYP450 metabolism
monitoring/side effects:
dry mouth, constipation, dyspepsia, headache
chemically it is polar so it cannot cross the BBB very well; less cognitive problems associated with Sanctura
possible interaction with drugs that may compete for renal tubular secretion: digoxin, morphine, metformin, vancomycin
cautions/contraindications: urinary retention, gastric retention, narrow angle glaucoma
FDA approval based on two 12 week trials
decrease in frequency vs. placebo
decrease in urge incontinence vs. placebo
increase in volume voided vs. placebo |
|
|
Term
treatment of detrusor instability (OAB):
Vesicare (solifenacin) |
|
Definition
MOA: antimuscarinic (M3 selective)
indication: OAB (urgency, frequency, UUI)
ADME:
well absorbed; with or without food
metabolism by 3A4 - inducers or inhibitors of 3A4 can alter kinetics
monitoring/ADRs: dry mouth, constipation, blurred vision, urinary retention, dry eyes
Vesicare can cause a lot of constipation (first studied as a drug for IBS)
cautions/contraindications: urinary retention, gastric retention, narrow angle glaucoma
3 fecal impaction/intestinal obstructions in trials
FDA approval based on four 12 week trials
decrease in frequency vs. placebo
decrease in urge incontinence vs. placebo
increase in volume voided vs. placebo |
|
|
Term
treatment of detrusor instability (OAB):
Enablex (darifenacin) |
|
Definition
MOA: antimuscarinic (M3 selective)
indication: OAB (urgency, frequency, UUI)
ADME:
bioavailability about 20% can be taken with or without food
metabolism via 2D6 and 3A4
monitoring/ADRs:
dry mouth, constipation, blurred vision, dyspepsia, abdominal pain
15 mg dose has a big jump in ADRs; 7.5 mg for older patients
cautions/contraindications: urinary retention, gastric retention, narrow-angle glaucoma
FDA approval based on four 12 week trials
decrease in frequency vs. placebo
decrease in urge incontinence vs. placebo
increase in volume voided vs. placebo
one study showed increased warning time
one study showed no effects on cognition; this study was done on patients with no cognitive problems (not studied in patients with cognitive problems or at risk for cognitive problems) |
|
|
Term
treatment of detrusor instability (OAB):
Toviaz (fesoterodine) |
|
Definition
MOA: antimuscarinic (non-selective)
indication: OAB (urgency, frequency, UUI)
dose: 4 mg QD, may increase to 8 mg QD
swallowed whole, do not crush or chew; with or without food
do not exceed 4 mg QD if taking 3A4 inhibitor or if CrCl < 30 ml/min
ADME:
metabolized by nonspecific esterases to 5-OH methyl tolterodine (active)
bioavailability 52%
active metabolite metabolized via 2D6 and 3A4 to inactive compounds
ADRs: dry mouth, constipation, blurred vision, dyspepsia, abdominal pain
no clinical advantage unless the patient is a poor metabolizer (2D6) |
|
|
Term
| effects of anticholinergic treatments for OAB |
|
Definition
reduce incontinence episodes by > 50%
reduce frequency episodes by about 20%
increase bladder storage (volume voided)
decrease urgency episodes
may decrease nocturia |
|
|
Term
| anticholinergic ADRs of OAB treatments |
|
Definition
dry mouth
dry eyes
constipation
urinary retention (if dose too high)
CNS/cognitive side effects
iris/ciliary body = blurred vision
lacrimal gland = dry eyes
salivary glands = dry mouth
heart = tachycardia
stomach = dyspepsia
colon = constipation
bladder = retention
muscarinic receptors are widely distributed throughout the body
in addition to the bladder, these receptors are located in a variety of organs of the parasympathetic nervous system, as well as in the CNS
common CNS ADRs are dizziness, somnolence, and impaired memory and cognition |
|
|
Term
| use of anticholinergic agents in patients with dementia/AD |
|
Definition
cholinergic system is damaged in dementia and AD
those with dementia/AD are sensitive to cognitive impairment induced by drugs with anticholinergic properties
ADRs related to:
total anticholinergic "load"
baseline cognitive function
individual pharmacokinetic and pharmacodynammic variability
when appropriate, the goal is to eliminate the use of anticholinergic agents or substitute with an agent that has less anticholinergic effects |
|
|
Term
| roles of muscarinic receptor subtypes in the CNS |
|
Definition
all 5 muscarinic receptor subtypes are expressed in the brain, and are located both pre and post synaptically on cholinergic neurons and on interneurons
M1
selective impairments of memory function
working memory, consolidation
M1 receptors play a critical role in modulating cognitive function
M2
learning and memory deficits; antagonists shown to enhance memory and facilitates recovery from brain injury
thought to be involved in inhibition of ACh release
M3
no major deficits in learning, memory, or cognitive function
M4
antagonists shown to enhance ACh levels in striatum
M5
no major deficits in learning, memory, or cognitive function |
|
|
Term
| passive and active efflux transport across the BBB |
|
Definition
increased lipophilicity = increased diffusion
increased charge/polarity = decreased diffusion
decreased molecular bulkiness = increased diffusion
also present in the BBB are a number of protein transport systems, which act as either active efflux systems for certain molecules (P-glycoprotein (Pgp) pump) or mediate influx of nutrients |
|
|
Term
| comparison of antimuscarinic OAB medications' ability to cross BBB |
|
Definition
unlike oxybutynin, tolterodine, and darifenacin, which are tertiary amines, trospium has a quaternary amine structure. as such, trospium has a highly positive charge, is hydrophilic in nature, and is not thought to cross the BBB under normal physiological conditions
darifenacine is selective for the M3 receptor subtype and is a known substrate for the Pgp efflux pump |
|
|
Term
| treatment of functional incontinence |
|
Definition
aim: remove underlying cause - sedative hypnotic drugs
scheduled bathroom visits
bedside commode
assist with functional disabilities (walkers) |
|
|
