TABLE 129-2 Pharmacologic Action on the Bladder

Drug
Indication
Mechanism
Cholinergic
Areflexic bladder
Muscarinic receptor
Bethanechol
agonists
Bladder has M2 and
M3 receptors; M3
receptors are
responsible for normal
detrusor contraction
Anticholinergics
Hyperreflexic bladder Mucarinic receptor
Hyoscyamine
antagonists
Oxybutynin
Tolte rodine
Trospium chloride
(quaternary amine)
Darifenacin
Solinefacin
Sympathomimetics
Open bladder neck
-Receptor
Norepinephrine
antagonists
Pseudoephedrine
Antiadrenergics
Smooth sphincter
-Receptor agonists
( blockers)
dyssynergia
Phenoxybenzamine (competent,
Phento amine
nonrelaxing bladder
Terazosin
neck)
Doxazosin
Tamsulosin
Alfuzosin
Tricyclic
Hyperreflexic bladder Anticholinergic and
antidepressants
with stress
sympathomometic
Amitriptyline
incontinence
properties
Imipramine
Benzodiazepines
Chlordiazepoxide
Baclofen

Dantrolene

Extremity spasticity
with detrusorsphincter dyssynergia
Extremity spasticity
with detrusorsphincter dyssynergia

Extremity spasticity
with detrusorsphincter dyssynergia

Side Effects and Cautions

Bronchospasm, miosis

Constipation, dry mouth,

tachycardia

Arrythmia, hypertension,
coronary, vasospasm,
excitability, tremors
Orthostatic hypotension,
dizziness, rhinitis,
retrograde ejaculation

Myocardial infarction,
tachycardia, stroke,
seizures, blood dyscrasias,
dry mouth, drowsiness,
constipation, blurred vision
GABA channel
Dizziness, drowsiness,
activator; centrally
extrapyramidal effects,
acting muscle relaxant ataxia, agranulocytosis
GABA-B channel
Central nervous system
activator (?); exact
depression, cardiovascular
mechanism unknown; collapse, respiratory failure
centrally acting
seizures, dizziness,
muscle relaxant
weakness, hypotonia
constipation, blurred vision
Direct muscle relaxant Hepatic dysfunction,
by calcium
seizures, dizziness,
sequestration in the
weakness, hypotonia
sarcoplasmic
constipation, blurred vison

Botulinum toxin

Detrusor-sphincter
dyssnergia

reticulum
Inhibits release of
acetylcholine

Repeated injection
necessery

Differential Diagnosis
The diseases listed in Table 129-1 are the most common causes of neurogenic bladder.

The sonographic correlate of detrusor sphincter dyssnergia is shown in Figure 129-4B

(nonrelaxation of the urethral sphincter is demonstrated).
TREATMENT
Initial
The priorities of bladder management relate first to preservation of renal function and abolition
of infection and second to social concerns. Overflow incontinence, ureteral reflux, or high
bladder pressures in the presence of renal insufficiency or active infection must be managed
aggressively by ensuring proper egress for urine. A source for persistent infection, such as
urinary lithiasis, must be sough and, if found, eliminated. High bladder pressure, particularly if it
is sustained (>40cm H2O), ultimately results in deterioration of renal function and should
therefore be addressed actively, even if renal function is normal.18
Patients at risk for degenerative neurogenic bladders, particularly those with (or at risk for)
sensory neuropathies (e.g., diabetic patients, phenytoin users), should have a timed voiding
schedule to prevent overdistention and progression to bladder areflexia. A 24-hour voiding diary,
including fluid intake, time and quantity voided, and postvoid residual (by catheterization or
ultrasound evaluation), should be recorded periodically. These patients should void every 6
hours, void again immediately after the first void, and adjust their fluid intake and voiding
frequency according to the voiding diary. Patients with diabetes should be careful to maintain
good glycemic control, not only for global prevention of degenerative disease but also to prevent
osmotic diuresis.
Most neurogenic bladder are associated with impaired bowel function, fecal impaction and
obstipation not only place the patients at risk for colon perforation, they may also cause
mechanical obstruction to the passage of urine. Further, many of the medications used to reduce
bladder contractility, particularly the anticholinergics, exacerbate bowel motile dysfunction. It is
therefore important that these patients be routinely prescribed high-fiber diets, stool softeners
(e.g., docusate, 100 mg orally, three times daily), laxatives (e.g., psyllium, 1 packet orally
everyday), and suppositories (e.g., bisacodyl, 10 mg per rectum every day) and undergo digital

stimulation either daily or every other day. Digital stimulation is best performed after either a
meal or coffee or tea to take advantage of the gastrocolic reflex.
The Crede method (suprapubic pressure) alone can lead to high intravesical pressure and even
vesicoureteral reflux. Such pressure, or persistent tapping of the suprapubic region for 2 minutes
at a time, should be performed only when methods to relieve bladder outlet obstruction have
been ensured. This should not be performed in patients with active detrusor-sphincter dyssenriga
because it will only exacerbate already high bladder pressures, and urine will not be completely
evacuated.

Acute Phase and Central Nervous System Shock

This phase usually lasts day to weeks but sometimes persists for months. The bladder is areflexic
during this periode, and adequate bladder drainageshould be secured to prevent the areflexic
bladder from developing overdistention and myogenic failure. Indwelling continuous Foley
catheterization (14 Fr) is the easiest way to ensure bladder drainage. Alternatively, intermittent
catheterization may be performed (after the initialphase of diuresis) and, when it is used from the
onset, reduces the incidence of infection and stone disease.19
Catheterization is performed every 4 to 6 hours and fluid is restricted to 2 liters per day, if
possible. The frequency of catheterization should be adjusted so that residuals are no more than
300 to 400 mL. for patients with hyperflexic bladder, long-term intermittent catheterization
requires mitigation of detrusor reflex with anticholinergic medication (see Tabell 129-2) to
reduce bladder pressures to safe levels (below 40 cm H2O) and to achieve continence between
catheterization.

Anticholinergic Drugs (Drugs to Increase Bladder Capacity)

In the human being, bladder (detrusor muscle) has muscarinic receptors (M2 and M3 receptors).
M3 compared with M2 are small in number but are mainly responsible for bladder contraction.
The antimuscarinic drugs oxybutynin, tolterodine, darifenacin, solifenacin, and trospium are the
five major drugs (Table 129-3) currently available to modulate detrusor hyperreflexia, to increase
bladder capacity, and to reduce baldder voiding pressures. Comparative clinical studies have
shown that oxybutynin and solifenacin may be marginally more effective than tolterodine,
although tolterodine seems to be better tolerated. Dry mouth and constipation are still major
problems for compliance of patients with all of them because of the widespread existence of M3
receptors, particulary in the salivary glands. Except for trospium chloride, most others shown in
Table 129-3 are tertiary amines and cross the blood brain barrier, enhancing anticholinergic
factor. There is evidence that they may lead to some loss memory.20

Autonomic Dysreflexia
The control of widespread sympathetic activity below the spinal lesion is the key factor in the
management of autonomic dysreflexia, and prevention is the first concern. Noxius stimuli, such
as overdistention of the bladder, should be reversed immediately by catheter drainage. Local
instillation of 25 to 50 mL of 0.3% tetracaine through the Foley catheter or suprapubic tube may
provide topical anesthesia of vesical mucosa and reduce triggering imulses to the spinal cord.
Consideration of procedures for patients at risk (spinal lesion above T6) should include spinal
anesthesia, use of ganglion blockers.
In the acute episode, if reversal of the noxius stimulus fails to control symptoms, administration
of nifedipine (30 mg orally)21 or nitropaste (about 1 inch applied on the body surface) is usually
adequate to reduce blood pressure. Note that normal blood pressure for a patient with spinal cord
injury is less than 10 mm Hg systolic. If nifedipine fails, hydralazine (10-20 mg intravenousely
or 10-50 mg intramuscularly) may be administrated. Use lower doses initially and repeat every
20-30 minutes as necessary to maintain a low blood pressure. Other useful drugs include
blockers (such as prazosin, terazosin, guanethidine, and clonidine) and anticholinergics (such as
oxybutynin and tolterodine). For long-term management of subacute autonomic dysreflexia,
clonidine (0.1 to 0.3 orally twice daily) is useful. Note that the chronic form of this syndrome is
often related to active detrusor sphincter dyssynergia, and methods aimed at control of this
phenomeno, such as transuretheral sphincterotomy, may alleviate the patient of autonomic
dysreflexia.22

Urinary Tract Infection

For those who have indwelling Foley catheter for extended period (more than several days) and
require catheter removal or exchange, antibiotics should be administrated prophylactically
before, during, and after removal of the existing catheter. Gentamicin (80 mg intramuscularly
once just before removal of the catheter) is appropriate for most patients with stable renal
function, even if function is impaired, and has both fram-positive and gram-negatve coverage.
TABLE 129-3 Summary of Anticholinergic Agents
Anticholinergic

T1/2(h)

Typical Side Effects

Comments

Oxybutynin

2-3

Dry mouth, constipation,

blury vision,headaches

Typical dose is 5 mgorally tid

Ditropan

Elderly: cognitive
impairment, hallucinations
Ditropan

13

Same as oral oxybutynin

Slower absorption with more

XL

stable blood concentration

Typical dose is 10 mg orally
daily but doses up to 40 mg
daily are generally safe

Oxytrol (oxybutynin
patch)

2-5

Same as oral oxybutynin, plus

local skin irritation

Bypasses first pass of the liver

which reduces the
concentrations of active
metabolites that are thought to
contribute to side effects
Dosed at 3.9 mg/day 1, patch,
2 times/week, alternating skin
sites

Tolterodine

2-10

Same as oral oxybutynin

Detrol

Possibly more selective to

urinary M receptors resulting
in fewer side effects
Typical dose is 2 mg orally
bid

Detrol LA

2-10

Same as oral oxybutynin

Slower absorption with more

stable blood concentration
Typical dose is 4 mg orally
daily

Danfenacin (Enablex)

13-19

Same as oral oxybutynin

Typical dose is 7.5 mg or 15

mg orally daily

Trospium

20

Same as oral oxybutynin

Quarternary amine does not

cross the blood brain barrer
well, resulting in minimal
central nervous system
anticholinergic effect, and it
may limit cognitive side
effects (particularly in the
elderly).
Typical dose is 20 mg orally
bid

Sanctura XR

36

Same as oral oxybutynin

More stable blood

consentration
Typical dose is 60 mg orally
daily
Solifenacin
(VESIcare)

45-68

Same as oral oxybutynin

Typical dose is 5 mg or 10 mg
orally daily