consideringsurgicalinterventionorinunchanged

frequency and nocturia.3 Treatment of OAB is

or worsened incontinence following treatment.

based on diagnosis after excluding other pathol-

They are useful in providing insight into blad-

ogies, i.e., urinary tract infection, bladder stone,

der pathophysiology. Urodynamics are strongly

diabetes. Options include conservative manage-

encouraged before proceeding with an invasive

ment, pharmacotherapy, and invasive/surgical

therapy. In patients with SUI,Valsalva leak point

measures. The principles of treatment are to

pressure (VLPP) is utilized. This is usually

increase voided volumes (thereby reducing fre-

assessed with bladder volumes greater than

quency and nocturia), decrease urgency, and

150 mL, and repeated every 50 mL until the

reduce UUI episodes.34

maximum cystometric capacity is reached.

A methodology for performing VLPP has not

Conservative Treatments

been standardized. There can be discrepancies

in pressure measurements due to catheter size,

A combination of lifestyle interventions, pelvic

floor muscle exercises (Kegel exercises), and

maneuvers.45 Some feel that VLPP is a measure

bladder

training

are the initial

management

of the severity of incontinence and can differen-

options

for OAB

sufferers. Lifestyle interven-

tiate ISD from urethral hypermobility.46

In a

tions include reduction of fluid intake, avoiding

study of 424 women, no association was found

fluid intake prior to bedtime, emptying bladder

between VLPP and a Q-tip test to assess urethral

before

leaving home and

prior

to

bedtime,

hypermobility.47 A majority of men with PPI

tobacco

cessation,

weight

loss,

and

caffeine

suffer from ISD, but only 25–50% will have ISD

avoidance. Bladder

training

and

pelvic floor

Urodynamics

are

muscle

exercises

are usually

complementary.

essential in these cases to identify detrusor over-

Bladder training aims to regain bladder control

activity, poor compliance, or bladder dysfunc-

by suppressing involuntary

detrusor

contrac-

tion prior to planning surgery.

tions through negative feedback. This in turn

There are conflicting opinions on use of pre-

increases voided

volumes

and time

interval

operative urodynamics in patients with MUI.

between voids, which improves voiding pattern.

There is a wide range of variability in bladder

Patients are taught to tighten their pelvic floor

sensation of a patient with urgency observed

during an involuntary contraction and when

during urodynamic investigation. For example,

going from a lying down to sitting or sitting to

some patients with detrusor overactivity (DO)

standing position.34,51

demonstrate high-pressure contractions with

very little sensation, while others have debilitat-

ing urgency with minimal rise in detrusor pres-

Pharmacotherapy

sure.41 In the Stress Incontinence Surgical

Treatment Efficacy Trial, including 655 women

Stimulation of muscarinic receptors in the blad-

randomized to either a Burch suspension or

der by acetylcholine leads to the contraction of

autologous sling, there was no difference in out-

the detrusor muscle. Therefore, anticholinergic

comes between those with or without detrusor

(antimuscarinic) drugs are the pharmacologic

overactivity.49 Yet, in a series of 144 women with

choice for OAB. These drugs were believed to act

symptomatic MUI undergoing tension-free vag-

primarily on parasympathetic efferents to the

inal tape (TVT), transobturator tape (TOT), or

bladder, but there is increasing evidence that

suprapubic arc (SPARC), DO was associated

there are also important afferent pathways.52

with a threeto fourfold increase in treatment

Additional focus is on sacral reflexes that poten-

tiate detrusor activity. This may help patients

with nocturia, many of whom have been largely

unresponsive to the mostly efferent changes

associated with anticholinergic agents. A major

goal with pharmacotherapy is to minimize the

side effects associated with anticholinergics in

The International Continence Society (ICS)

order to avoid the historic, seemingly insoluble

defines overactive bladder (OAB) as urgency,

problem of noncompliance. New transdermal

with or without UUI, usually associated with

delivery systems based on patch therapy and

442

PRaCtiCal URology: ESSEntial PRinCiPlES and PRaCtiCE

depot platforms are being developed and have

there were significant reductions at 7.5 mg

the major advantage of being long-acting. The

(67.7%) and 15 mg (72.8%) compared to placebo

transdermal system bypasses first-pass metabo-

(55.9%) in UUI episodes per week, voiding fre-

lism in the liver and gut, reducing the amount of

quency, urgency, and number of UUI episodes

the metabolite N-desethyloxybutynin (oxybu-

leading to a change in clothing.

tynin metabolite) in the blood. In 2004, the USA

Recent interest has focused on resiniferatoxin,

Food and Drug Administration approved four

a naturally occurring capsaicin-like agent

new drugs for the treatment of OAB in men and

derived from the plant Euphorbia resinifera.

women: darifenacin, solifenacin, tolterodine,

Capsaicin is a potent neurotoxin that desensi-

and trospium.

tizes the bladder’s afferent C-fibers when

The interaction of widely dispersed muscar-

instilled intravesically. Resiniferatoxin is 1,000

inic receptors is poorly understood. The M1

times more potent than capsaicin.56 In neuro-

receptors in the brain and salivary glands have a

logically intact patients, reflex voiding is initi-

role in the cognition and production of mucous

ated normally via capsaicin-resistant myelinated

saliva. The M2 receptors in the cardiovascular

A-dbladder afferent fibers,57 while in spinal cord

system are involved in heart rate and cardiac

injuries, voiding involves stimulation of unmy-

output and the M5 receptors in the eye influence

elinated C-fiber afferents, which are sensitive to

ciliary muscle contraction. The binding of some

neurotoxin.58,59 Fowler et al.60 found that intra-

or all of the antimuscarinics listed with these

vesical capsaicin caused symptomatic and uro-

different receptors leads to the side-effect pro-

dynamic improvement in 60–100% of patients

file: cognitive impairment, tachycardia, dry

with detrusor hyperreflexia and intractable UUI,

mouth, or blurred vision. The classic drug oxy-

lasting up to 1–9 months. No systemic toxic

butynin has a high affinity for the M1 and M3

effects were seen. There was a temporary neu-

receptor subtypes. Darifenacin and solifenacin

ronal excitation phase of the primary afferent

both are M3-selective antagonists, with selectiv-

neurons (temporary acute pain and bladder

ity for the bladder over the salivary glands, thus

hyperactivity) following initial capsaicin instil-

reducing the characteristic dry mouth seen with

lation. Resiniferatoxin is not associated with this

oxybutynin. Tolterodine is a specific and potent

initial excitation. In 20 neurologically impaired

competitive antagonist of muscarinic receptors,

patients with detrusor hyperreflexia, sequen-

but has no significant selectivity for receptor

tially increasing intravesical doses of resinifera-

subtypes. Trospium chloride is a quaternary

toxin were given. Bladder capacity increased

ammonium compound which does not cross the

and UUI improved in 8 of 13 patients. Bladder

blood-brain barrier, ideally preventing cogni-

discomfort was well tolerated.61

tive effects4 associated with antimuscarinics.

Invasive/ Surgical Therapies

The Overactive Bladder: Performance of

Extended Release Agents (OPERA) Study53 com-

Botulinum toxin (BTX) is a potent neurotoxin

pared the efficacy and tolerability of extended-

release oxybutynin (OER) and extended-release

that inhibits acetylcholine release at the presyn-

tolterodine (TER). OER was found to be superior

aptic cholinergic junction, inducing detrusor

in reduction of micturition frequency, while TER

muscle relaxation and potentially affecting

was associated with a lower rate of dry mouth.

afferent sensory receptors in the urothelium.62

The Solifenacin and Tolterodine as an Active

Recent evidence supports additional action of

comparator in a Randomized Trial (STAR)

BTX on neurotransmitters other than acetyl-

Study54 was a prospective, double-blind, two-arm

choline as cause of sensory effects. BTX-A (sero-

study comparing the safety and efficacy of solif-

type A toxin) was first investigated 20 years ago

enacin and TER. There was no difference in

for urological indications, i.e., treating detrusor

reduction in mean number of micturition epi-

external sphincter dyssynergia following spinal

sodes per 24 h, yet solifenacin was more effective

cord injury. Use of BTX-A for neurogenic detru-

in decreasing daily episodes of urgency, UUI, and

sor overactivity was first described in 1999. All

incontinence. Haab et al.55 reported on data from

studies to date demonstrating idiopathic detru-

the European trial of darifenacin with 561

sor overactivity showed improvement in urody-

patients randomized to once-daily controlled-

namic parameters and symptoms with BTX.

release darifenacin tablets or placebo.At 12weeks,

There were symptomatic improvements in