Voiding Function

“Toddlers to Retirees”
April 6, 2006
Christopher French MD FRCSC
Adult and Pediatric Surgery
The Voiding Continuum
 Potty Training 2
 Bumps along the road 4
 Normal Voiding pattern or sometimes
established dysfunctional voiding
 Overactive Bladder
 It’s my prostate, doc. >50
 The aging bladder >70
Clinical Focus on VUR and BPH
 Vesicoureteral reflux
 Deflux “sting’ procedure

 BPH
 Identifying patients who have symptoms
related to the enlarged prostate (or is it an
aging bladder)
The Voiding Continuum
 Potty Training
 Why not start early
 Development window
 Recurring patterns
 Parenting styles
The Voiding Continuum
 Potty Training
 Chinese culture- children learn at their own time
 Much less dysfunctional voiding in china
 Is this reporting? What if asia becomes more
westernized?
 Pediatric Urologists generally don’t recommend
potty training prior to 18mo of age. There is
weak evidence that these children are more
likely to become dysfunctional voiders
The Voiding Continuum
 Bumps along the road
 Dysfunctional voiders
 Constipation
 Anxiety
 Recurring cystitis
 A toddler will hold as a response to painful voiding
 A bladder that doesn’t empty always feel full
The Voiding Continuum
 Overactive Bladder
 Typically this is urinary frequency without pain, occurs in
men and women in adultyears
 Multifactorial
 Age 30-50 typically
 Change in body habitus, pelvic fatty deposition,
abdominal girth.
 Long time dysfunctional voiders may develop autonomic
sensitivity and this may lead to conditions sometimes
described as interstitial cystitis
The Voiding Continuum
 It’s my prostate, doc.
 All voiding problems for men tend to lay blame on the
prostate
 OAB symptoms in a 40 man is rarely BPH
 But a 60 yo man with symptoms associated with slow
stream is classic for BPH
 Men over 80 are more likely to have some degree of
impaired contractility. (maybe the BPH becomes
symptomatic more at this point)
The Voiding Continuum
 The aging bladder
 The bladder muscle weakens with age
 Urodynamically impaired contractility
 Men and women in their 80’s
 Men tend to have a component of BPH and thus may
respond to treatment
 General vascular impairment ages the bladder
 Diabetics and PVD patients are more likely to have
poorly contractile bladders.
The Voiding Continuum
 Potty Training
 Bumps along the road
 Normal Voiding pattern or sometimes
established dysfunctional voiding
 Overactive Bladder
 It’s my prostate, doc.
 The aging bladder
VUR: raising the standard

An educational meeting
for
Pediatric Surgeons/Adult
Vesicoureteral Reflux
(VUR)

Introduction to VUR
Prevalence

 Affects approximately 1% of all children

 Found in 30–40% of children with recurrent
urinary tract infections
 Most children are <4 years of age
 75–80% of children diagnosed with VUR are
girls
 Some congenital anomalies of the
genitourinary tract are associated
with a high percentage of VUR

[Sargent MA. Pediatr Radiol 2000; 30: 587]

Prevalence

(percentage of the general pediatric population)

Prevalence of VUR

Average Age
[Reproduced with permission]
[American Academy of Pediatrics. Pediatrics 1999; 103: 843]
Prevalence

 Factors known to affect the risk of VUR

include:
 Age
 Gender
 Race
 Family history
 These factors likely contribute to
variations between prevalence studies
Who to screen
 Family history:
 Sibling with reflux (incidence 24–
51%)
 Many of these children have no
documented history of symptomatic
infection
 Young children are at the greatest risk

 Parent with reflux (incidence 66%)

 Screen all siblings and offspring
of patients with known VUR
[Chertin B and Puri P. J Urol 2003; 169: 1804.
Noe HN et al. J Urol 1992; 148: 1869]
Who to screen (cont’d)
 Children with other urologic
conditions:
 Antenatal hydronephrosis
 Prune belly (Eagle Barrett) syndrome
 Solitary kidney
VUR and bladder
dysfunction
 Approximately half of children with
VUR have detrusor activity and/or
voiding dysfunction
 In these patients, bladder training
is usually undertaken initially
VUR and the risk of UTI
 VUR predisposes to infection of the upper urinary
tract
 Presence of reflux facilitates spread of infected urine
towards the kidneys
 Associated likelihood of febrile illness and
pyelonephritis – increased morbidity
 Significant reduction in febrile UTI observed
among VUR patients treated with open surgery
Potential complications of
VUR
 Renal scarring
 Impaired renal growth and renal function
 Hypertension
 End stage renal disease
 Pregnancy complications
 Pre-eclampsia
Renal scarring
 Incidence of renal scars at diagnosis
of VUR: 5–30%
 Risk of new renal scars: ~2–5%/year
(with antibiotic prophylaxis)
 5.6% of children undergoing kidney
transplantation had the primary diagnosis
of reflux nephropathy (RN)
 Of patients ≥ 15 years of age with reflux
nephropathy:
 24% had impaired kidney function
 38% had hypertension

[Benfield MR et al. Pediatr Transplant 1999; 3: 152.

Zhang Y et al. N Z Med J 1995; 108: 142]
Renal scarring
 Surgical intervention for VUR reported to
have no significant effect on renal outcome
versus antibiotic prophylaxis
 Also no decrease in the incidence of
VUR-associated end-stage renal disease

Likely explanation:
 Presence of reflux prenatally, or UTI during
early infancy, may be the primary risks for
renal impairment
The need to treat VUR
 Reduce UTI-associated morbidity
 Eliminate on-going health problem
 Avoid the need for future VCUG examinations
 No evidence of improved renal prognosis but
ethical arguments in support of intervention,
particularly in high-risk cases
 Without treatment, reflux persists for at least 4–
5 years in at least half of all cases
Conclusions
 Antibiotic prophylaxis may be appropriate
in grade I VUR or in infants, but:
 Potential for development of resistance
 Issues of compliance
 Open surgery is associated with high cure
rates but carries some risk of
complications
 Endoscopic treatment provides a
minimally-invasive treatment alternative for
most VUR grades
 Patients’ parents prefer this option
 Managing Patients with
Vesicoureteral Reflux (VUR)
Management/treatment
options
 Medical
 Antibiotic prophylaxis
 Open surgery: ureteral
reimplantation
 Intravesical (Cohen, Politano–
Leadbetter)
 Extravesical (Lich–Gregoir,
detrusorrhaphy)
 Endoscopic injection
 Deflux®
Endoscopic treatment:
historical perspectives
 Technique first investigated >20
years ago
 Rationale, circa 1984:
 Open surgery entailed hospitalization
for ≥1 week
 Surgery not free from complications
 First injectable agent approved by
FDA in 2001

[O’Donnell B and Puri P. Br Med J (Clin Res Ed) 1984; 289: 7]

Endoscopic treatment:
STING
 Support under the refluxing ureteric orifice
 Improved valve mechanism
 Fixation of the distal ureter at the
ureterovesical junction
 Increased submucosal tunnel length

Bladder
Ureter mucosa
Deflux
injection

Bladder wall
Endoscopic treatment:
advantages
 Like open surgery, a curative
treatment
 Outpatient procedure
 30-minute operating room time
 Usually, no need for hospitalization
 Efficacy rates can approach those
with open surgery (depending on
reflux grade, injection technique and
experience with the procedure)
Endoscopic treatment:
disadvantages
 Cure is generally less certain than
with open surgery
 Possible need for repeat
treatments
 Poorly recognized in the present
AUA guidelines (published 1997)
 Anesthesia still required
Endoscopic treatment:
outcomes
 Overall cure rates approximately
70–80%
 Cure rates potentially affected by:
 Reflux severity (grade)
 Surgeon’s experience
 Injection technique
 Need to consider long-term
durability of treatment response
[Austin JC & Cooper CS. Urol Clin North Am 2004; 31: 543.
Läckgren G et al. AUA Update series 2003; Volume XXII, Lesson 37: 294]
Endoscopic treatment:
learning curve
Success (%)

Cases
[Reproduced with permission]
[Kirsch AJ et al. J Urol 2004; 171: 2413]
AUA guidelines for managing
VUR
 Published in 1997
 before US introduction of Deflux®
 Extensive literature review: 1965–1994
 Seven treatment modalities were examined:
 Treatment outcomes examined for each
(resolution of reflux, incidence of UTIs, renal
scarring etc)
 Treatment recommendations developed on
the basis of these data
 Stepwise decision-making process is
summarized on the following slides

[AUA treatment guidelines 1997, www.auanet.org]

AUA guidelines: infants
(<1 year old)
No renal scarring
 Grade I–V reflux: antibiotic prophylaxis
 Persistent grade I–II reflux: no consensus
 Persistent grade III–V reflux: open surgery

Renal scarring present at diagnosis

 Grade I–IV reflux: antibiotic prophylaxis
 Grade V reflux: antibiotic prophylaxis or open surgery
 Persistent grade I–II reflux: no consensus
 Persistent grade III–V reflux: open surgery

[AUA treatment guidelines 1997, www.auanet.org]

AUA guidelines: pre-school
children (1–5 years old)
No renal scarring
 Grade I–IV: antibiotic prophylaxis
 Grade V: antibiotic prophylaxis or open surgery (bilateral:
open surgery is preferred)
 Persistent grade I–II: no consensus
 Persistent grade III–V: open surgery

Renal scarring present at diagnosis

 Grade I–IV reflux: antibiotic prophylaxis (bilateral grade
III–IV: open surgery is a reasonable alternative)
 Grade V: open surgery
 Persistent grade I–II: no consensus
 Persistent grade III–V: open surgery

[AUA treatment guidelines 1997, www.auanet.org]

AUA guidelines: school
children (6–10 years old)
No renal scarring
 Grade I–II: antibiotic prophylaxis
 Grade III–IV (unilateral): antibiotic prophylaxis
 Grade III–IV (bilateral): open surgery
 Grade V: open surgery
 Persistent grade I–II: no consensus
 Persistent grade III–IV: open surgery

Renal scarring present at diagnosis

 Grade I–II: antibiotic prophylaxis
 Grade III–IV (unilateral): antibiotic prophylaxis
 Grade III–IV (bilateral): open surgery
 Grade V: open surgery
 Persistent grade I–II: no consensus
 Persistent grade III–IV: open surgery
[AUA treatment guidelines 1997, www.auanet.org]
Proposed new treatment
algorithm
 Announced in 2003
 Reconsideration of the treatment
options for VUR
 Major difference from 1997:
availability of Deflux®
 Introduction of endoscopic
treatment as a routine treatment
option

[Läckgren G et al. AUA Update Series 2003; Vol XXII, Lesson 37: 294]
Proposed new treatment
algorithm

*Deflux is approved in the USA for reflux grades II–IV and

in children over 1 year of age.
[Reproduced with permission]
[LäckgrenG et al. AUA Update Series 2003; Vol XXII, Lesson 37: 294]
Advantages of the new
algorithm
 Reduced use of antibiotics
 Reduced number of children
undergoing open surgery
 Patients’ parents prefer endoscopic
treatment over open surgery
 Reduced operating room time
Conclusions
 Antibiotic prophylaxis may be appropriate in
grade I VUR or in infants, but:
 Potential for development of resistance
 Issues of compliance

 Open surgery is associated with high cure

rates but carries some risk of complications

 Endoscopic treatment provides a

minimally-invasive treatment alternative for
most VUR grades
 Patients’ parents prefer this option
Antibiotic Use in VUR:
Issues and
Considerations
Spontaneous resolution
rate

100
90 Year 5
80 Year 4
Resolution (%)

70 Year 3
60 Year 2
50 Year 1
40
30
20
10
0
Grade I Grade II Grade IV - Grade IV -
unilateral bilateral

It takes at least 5 years for grade II

reflux to resolve in 80% of cases
[Elder JS et al. J Urol 1997; 157: 1846]
History of prophylaxis
 Antibiotic prophylaxis was first
conceptualized >40 years ago

 Based on limited data from early studies:

 75 children with VUR aged 3 weeks to 12 years
received continuous low-dose prophylaxis
 Followed for 7–15 years
 71% spontaneous resolution of VUR
 2 cases of new scarring

 Early observations of efficacy have not

been reproduced [Normand ICS and Smellie JM. BMJ 1965; 17.
Edwards D et al. BMJ 1977; 2: 285]
Antibiotic prophylaxis: renal
protection
 The International Reflux Study in Children:
12% (19/155) of medically-treated patients
developed new scars during 5 years of follow-
up

 Preliminary report of the Southwest

Pediatric Nephrology Study Group:
10% of medically-treated patients with
grade I–II VUR, and
28% of patients with grade III VUR
developed new scars during 5 years of
[Arant BS, Jr. J Urol 1992; 148: 1683.
follow-up Olbing H et al. J Urol 1992; 148: 1653]
Incidence of breakthrough
urinary tract infections
 Approximately 20–40% of patients will
develop UTIs while on antibiotic prophylaxis for 5
years

 Infections experienced during ongoing antibiotic

prophylaxis can result from:
 Lack of patient compliance with the treatment regimen
 Resistant bacterial strains

[Arant BS, Jr. J Urol 1992; 148: 1683.

Wheeler D et al. Arch Dis Child 2003; 88: 688]
Patient compliance
 Missed doses:
 Leave the patient open to UTIs
 Exacerbate the risk of antibiotic resistance

 Poor compliance is more likely:

 In younger children
 During long-term antibiotic use

[Hoppe JE et al. Pediatr Infect Dis J 1999; 18: 1085]

Patient compliance
(cont’d)
 584 children with bacterial infection requiring oral antibiotics
 Most common infections: tonsilitis, otitis media, lower respiratory tract infection, upper
respiratory tract infection and sinusitis
 Antibiotics received: amoxicillin, penicillin, clarithromycin, cefaclor, erythromycin

 Compliance measured by telephone interview and urine bioassay

 Overall compliance rate (positive urine test) of 69.5%
 Negative urine test despite claiming regular administration: 28.8%

[Hoppe JE et al. Pediatr Infect Dis J 1999; 18: 1085]

Patient compliance
(cont’d)
 54 patients underwent bone marrow transplantation
 Oral antibiotics required post-transplantation
 Retrospective review of patient records:
 Only 48% complied with the oral antibiotic regimen
 Compliance was significantly lower in preschool and school-age
children compared with adolescents (p<0.05)

[Phipps S and DeCuir-Whalley S. J Pediatr Psychol 1990; 15: 459]

Compliance with antibiotic
prophylaxis decreases over time
100
84
Compliance (%)
80
57
60
40
20
0
6 months 12 months

n=69
[Panaretto K et al. J Paediatr Child Health 1999; 35: 454]
Urine concentrations of
the antibiotic during
prophylaxis

After 12 months of prophylaxis,

the urine of only 18% of VUR
patients tested positive for the
antibiotic

[Panaretto K et al. J Paediatr Child Health 1999; 35: 454]

The increasing problem of
antibiotic resistance
1985
 Resistance to commonly-
used antibiotics was low
 Many classes of antibiotics
were effective & available
 New antibiotic classes were
still being developed
2005
 Resistance to commonly-
used antibiotics is high &
increasing
 Reduced efficacy of
commonly used antibiotic
classes as a result of
growing resistance levels
 Few new antibiotic
products & classes in
development
Antibiotics commonly used in
patients with VUR
 Trimethoprim
 Trimethoprim-sulfamethoxazole
(TMP/SMX)
 Nitrofurantoin
 Sulfisoxazole
 Amoxicillin
 Cephalosporins, e.g. cephalothin (1st
generation), cefixime (3rd generation)
 Antibiotic indications
Antibiotic Pediatric Approved
indication? for
prophylaxi
s?
Trimethoprim- Yes – for treatment No
sulfamethoxa of UTIs. Not
zole recommended in
(TMP/SMX) children under 2
months of age.

Nitrofurantoin Yes – for No

treatment of acute
Resistance rates: USA 2004
Escherichia coli
50 45.1

40
Resistance (%)

30
21.8
20 13.9

10

0
Ampicillin TMP/SMX Cephalothin

[USA antibiogram results 2004]

Resistance rates among
urinary tract pathogens
 Study performed at a tertiary referral
pediatric center in Canada

 1,636 urinary tract isolates of Escherichia

coli (E. coli) analyzed from 967 children

 Reported resistance rates (1992–94)

 Ampicillin: 45% (736 isolates)
 TMP/SMX: 31% (514 isolates)
 Both: 22%

[Allen UD et al. CMAJ 1999; 160: 1436]

Multi-drug resistance: a
global problem
 Increase in hospital and community-acquired
cases worldwide

 Affects treatment of many diseases including

 Respiratory infections
 Skin and soft tissue infections
 Urinary tract infections

 Increased risk of treatment failure, even with

the newer antibiotic classes
[Manges AR et al. N Engl J Med 2001; 345: 1007.
Sharma SK and Mohan A. Indian J Med Res 2004; 120: 354]
Multi-drug resistance in
Europe
 46,948 Escherichia coli isolates from 25 European countries
(2001–2003)

 Antibiotic groups tested:

 Aminopenicillins
 Third generation cephalosporins
 Fluoroquinolones
 Aminoglycosides

 Multi-drug resistance level (to three or more antibiotics): 4%

[EARSS annual report 2003]

Multi-drug resistance in the
USA
 38,835 urinary tract isolates of
Escherichia coli (January–September 2000)

 Multi-drug resistance level (to three or more

antibiotics): 7.1%

Most (58%) multi-drug resistant strains were

resistant to ampicillin, cephalothin and
TMP/SMX

[Sahm DF et al. Antimicrob Agents Chemother 2001; 45: 1402]

 Ciprofloxacin resistance
trends in the USA
29
Pseudomonas
25
aeruginosa
30
23
27
20.5
20
Resistance (%)

17.5
15
10
5
0
1996 1997 1998 1999 2000

Resistance rates are increasing

rapidly, even to the newer
antibiotics such as ciprofloxacin
[Reproduced with permission]
[Livermore DM. Clin Infect Dis 2002; 34: 634]
Previous exposure to
antibiotics increases the risk
of resistance

Children who had taken antibiotics

for
>4 weeks during the previous 6
months
were 23 times more likely to have
TMP/SMX-resistant strains of E.coli

[Allen UD et al. CMAJ 1999; 160: 1436]

Implications of antibiotic
resistance
 Individual resistance: there is a high risk of
breakthrough UTI

 Community-acquired resistance: resistant strains may be

passed to individuals within the community

 Multi-drug resistance: second and even third-line antibiotics

may fail to treat the infection

 Hospital-acquired resistance: resistant strains may be

transferred between patients in hospital
Exposure to sub-inhibitory
antibiotic doses
 Urine samples taken morning, noon and
night from 14 children receiving TMP/SMX

 Sub-inhibitory concentrations were

observed in almost 1/3 of patients at 1 or
more time points

 Over 1/5 of samples had dropped into the

sub-inhibitory range by the evening

Exposure to sub-inhibitory antibiotic

concentrations
encourages development
[Pomeranz Aof resistance
et al. J Urol 2000; 164: 1070]
Duration of exposure to
sub-inhibitory antibiotic
doses

 The overall bactericidal effect of

TMP/SMX was sustained for only
60% of a 24-hour period in
children with VUR
 No antibiotic coverage for at
least 40% of the day

[Pomeranz A et al. J Urol 2000; 164: 1070]

Inadequate dosing leads to
decreasing susceptibility over
time
100

80 AU C /MIC >100
Susceptible (%)

60
AU C /MIC <100

40

20

0
5 15

Days
Long-term exposure to low
concentrations of the antibiotic
encourages resistance [Reproduced with permission]
[Thomas JK et al. Antimicrob Agents Chemother 1998; 42: 521]
Association between
antibiotic prophylaxis and
resistance
Continuous antibiotic prophylaxis puts selective pressure on bacteria to mutate into drug-resistant strains


Low dosing increases the risk of exposure to sub-inhibitory concentrations



Poor compliance further reduces the dose received


prophylaxis an appropriate
management option for
VUR?

 Antibiotic resistance has become a serious

problem – in general practice and in hospitals

 A priority issue for the CDC and

WHO – classified as “epidemic”
It should be noted that antibiotic
prophylaxis does not cure the
underlying condition (VUR)
Deflux®: a natural
choice in the
treatment of VUR
The Deflux Formula
 Easily injectable, viscous gel made
from two polysaccharides
 Non-animal stabilized hyaluronic acid
(NASHA)
 Dextranomer microspheres (80–250
µ m)
NASHA

Dextranomer
microspheres
Hyaluronic acid

 Exists in all living

organisms
 Low potential for
hypersensitivity
reactions (<1%)
 Fully biodegradable
 Used extensively in eye
surgery and joint
injections
NASHA technology
 Hyaluronic acid is produced using
cultured bacteria
 Limited potential for allergic reaction

 The hyaluronic acid undergoes a

stabilization process
 Increased durability
Dextranomer
microspheres

 Polymer of glucose (cross-linked

dextran)
 Microspheres 80–250 µ m in
diameter
Deflux does not migrate
from the site of injection
Dextranomers labeled with 125 Iodine and mixed
with Deflux

Deflux injected into the submucosal space in the

bladder of 6 rabbits

Blood samples taken: Whole-body

1 hour, days 1–14, and autoradiography:
days 21 and 28 at days 1, 7 and 28

Tissue samples taken: brain, lung, liver, spleen and

bladder after 1, 7 and 28 days; urine was sampled
at the same times
[Stenberg ÅM et al. J Urol 1997; 158: 1937]
Deflux does not migrate
from the site of injection
Results

Thyroid Bladder
Thyroid Bladder

[Stenberg ÅM et al. J Urol 1997; 158: 1937]

Preclinical safety

Preclinical study: methods

Pigs (n = 9)
urinary bladder

Rats (n= 34)

subcutaneous
[Stenberg Å et al. Scand J Urol Nephrol 1999; 33: 355]
Histopathological results in
animals

Collagen
Dextranomers
fibers

Pigs Capsule

Rats Dextranomers
Blood
vessels
[Reproduced with permission]
[Stenberg Å et al. Scand J Urol Nephrol 1999; 33: 355]
Is Deflux safe in humans?
(histopathology)
Clinical study: method
 13 children aged 1–11 years, with persistent reflux grade
III–V following treatment with Deflux
 Referred for open surgery (ureteral reimplantation)
 10 patients with a similar reflux grade, but no previous
endoscopic treatment, were included as controls
 Sections of the Deflux implant were collected and
examined under the light microscope

[Stenberg A et al. J Urol 2003; 169: 1109]

Histopathological results in
humans
Dextranomer
Collagen

C
Capsule

Mast Ureter
cells

Eosinophiles
Ca precipitations

[Reproduced with permission]

[Stenberg A et al. J Urol 2003; 169: 1109]
Histopathological results:
conclusions
 The observed inflammatory reaction was a
natural and expected response to any
foreign substance being introduced into the
body

 No evidence of allergic reaction, granuloma

formation or development of tumors

 Infiltration of collagen fibers stabilizes the

implant, increasing long-term durability
The Deflux treatment procedure
Deflux: the treatment procedure
(Subureteric transurethral injection, STING)

Ureter Bladder

Positio
n of Cystoscope
the
Deflux
injectio
n Urethra
Deflux: the treatment procedu
(Subureteric transurethral injection, STIN
Items required for endoscopic
injection of Deflux
1) Cystoscope: minimum 4 Fr channel

[manufactured by Wolf]

2) Narrow metal needle

3) Pre-filled Deflux syringes
4) Video camera
5) Sodium chloride solution
 How and where Deflux is
injected

Ureter

Bladder wall Deflux is injected Deflux implant

into the bladder
submucosa,
2–3 mm below the
refluxing ureter
Technical aspects of Deflux
treatment: STING
• Semi-full bladder
• 6 o´clock position
• Inject submucosally
• Volcano shaped bulge
• Crescent-like orifice
Technical aspects of Deflux
treatment (cont’d)
Standard follow-up
procedure
 Ultrasound after 1 month
 Voiding cystourethrogram (VCUG)
after 3 months

Bulge
 Conclusion

 Both components of Deflux are biodegradable and

biocompatible (both have established medical
applications)
 Long-term persistence (post-treatment infiltration with endogenous collagen)
corresponds with a long-term clinical response (see efficacy section; long-term data
are being generated in an ongoing study in the USA)

 Low potential for allergic or immunogenic reactions

 Clinical Experience

Deflux is indicated for treatment of

children with vesicoureteral reflux
 Response to Deflux: early
data*
110 ureters with grade III–IV reflux treated
100
80 68
Ureters (%)

60
40
19
20 13

0
Resolved Improved Unchanged
(grade 0) (grade I/II) (grade III/IV)

Response to Deflux treatment

*STING technique [Stenberg A and Läckgren G . J Urol 1995; 154: 800]

Response to Deflux: recent
data*
100 89

Response rate 80 70
63
(patients, %) 60
40
20
0
II (n=35) III (n=30) IV
Ureters (n=8)
treated:
Baseline reflux grade

*STING technique [Kirsch AJ et al. J Urol 2004; 171: 2413]

Duration of response *

Study investigating Deflux* treatment

of VUR in uncomplicated cases
• Children over 12 months of age
• Persistent reflux, grade III–V†
• Contralateral reflux grade I–II also treated
• Patients with neurogenic bladder or those
who had received previous treatments for
VUR were excluded

Deflux is indicated for treatment of children with

†

vesicoureteral reflux (VUR) grades II–IV

*STING technique [Läckgren G et al. J Urol 2001; 166: 1887]
Duration of response*

 Study population: 221 patients, 1–15 years old

(72 boys, 149 girls; mean age 4.7 years)

 Followed clinically for 2–7.5 years

(mean 5 years)

 67 patients retreated (29%)

*STING technique [Läckgren G et al. J Urol 2001; 166: 1887]

Initial response rates *

VUR resolved (grade ≤ 1) in

68% of 221 patients, tested by
VCUG
3–12 months following Deflux
treatment

*STING technique [Läckgren G et al. J Urol 2001; 166: 1887]

The response to treatment
varies
100
with reflux grade*

Response rate 80 73

(patients, %) 60
59

40

20

0
III (n=149) IV (n=58)

Baseline reflux grade

Deflux is indicated for VUR grades II–IV

*STING technique [Läckgren G et al. J Urol 2001; 166: 1887]

Repeated treatments *

(if required)

60
Response rate
(patients, %)

40

20

0
1st treatment 2nd treatment
3rd treatment

*STING technique [Läckgren G et al. J Urol 2001; 166: 1887]

Long-term treatment effect *

 Lack of deterioration after initial response

 87% of ureters without reflux at
3–12 months post-treatment were
free from reflux at 2–5 years
of follow-up
 96% remained free of dilating reflux (grade III or
above)

*STING technique [Läckgren G et al. J Urol 2001; 166: 1887]

Referral to open surgery

Only 12% of patients were

referred for open surgery as a
result of persistent reflux (grade
III or above) 3–12 months
following Deflux treatment

[Läckgren G et al. J Urol 2001; 166: 1887]

Approved endoscopic
treatments
 Deflux was approved by the FDA in 2001 for the treatment of
children over 1 year of age with VUR grades II to IV

 Deflux is currently the only material approved by the FDA for this
indication

 Studies using the STING technique were fundamental to approval of

Deflux by the FDA
Standard treatment
procedure
 Implantation 2–3 mm below the
entrance to the ureter – subureteric

 Access to the bladder gained via the

urethra – transurethral

 Injection into the bladder submucosa

(Subureteric transuretral injection)

“STING”
Adaptations to the
procedure
 Pressurized steam passed into the
ureter – Hydrodistention
 Implantation into the ureteral
submucosa
 Combined into a modified Technique

(Hydrodistention-Implantation Technique)
“HIT”

The HIT is a recent adaptation and may have a

different adverse event profile from the
Results using the HIT
100 89

(patients, %) 80 71
Cure rate

60
40
20
0
ST ING HIT

(n=52) (n=70)
Procedure
[Kirsch AJ et al. J Urol 2004; 171: 2413]
Tolerability
 Deflux has been used in Europe for
over a decade
 30,000 children with VUR have been
treated worldwide

 Studies of Deflux treatment reveal:

 Low risk of complications
 No reported persistent adverse events
 No reported allergic reactions
 Risk of treatment-related
adverse events
Adverse Randomized Nonrandomized
event study (n=39) studies (n=170)

UTI 6 (15.4%)* 13 (7.6%)†

Ureteral 1 (2.6%) 6 (3.5%)
dilatation
Nausea/vomi 0 (0%) 2 (1.2%)
ting/Abdomi
nal pain
*Antibiotics continued for 1 month post-treatment.
†
Antibiotics continued for 3 months post-treatment and in cases of persistent reflux.
Risk of obstruction

The biodegradability of
Deflux allows a degree of
volume reduction after
injection, minimizing the risk
of obstruction

[Stenberg Å et al. Scand J Urol Nephrol 1999; 33: 355]

Contralateral reflux
• Contralateral reflux (de novo reflux in
the untreated ureter) is a possible
complication of both endoscopic
injection and open surgery

• De novo contralateral reflux has been

reported in between 5% and 16% of
patients following Deflux treatment in
recent studies

[Kirsch AJ et al. J Urol 2003; 170: 211]

Post-treatment options

If Deflux treatment has failed

to resolve the VUR, presence
of the implant does not
complicate subsequent
surgical procedures to correct
the reflux if required
Summary of Deflux tolerability
data
Study Tolerability information
Läckgr Free from complications in all
en 310 procedures. Post-treatment
2001 UTIs in 8% (19/221) of patients
during 5 years of follow-up.
Capozz Post-treatment UTIs in 6 of 39
a 2002 children – all successfully
treated with antibiotics.
Kirsch No hydronephrosis at 12 months
2003
[Läckgren Gof follow-up.
et al. New
J Urol 2001; 166: 1887. contralateral
Capozza N and Caione P. J Pediatr
2002; 140: reflux inet4.5%
230. Kirsch AJ al. J Urol (6/134).
2003; 170: 211. Kirsch AJ et al. J Urol
2004; 171: 2413]
Conclusion
 Most patients can expect to be cured (reflux
grade 0) following Deflux treatment*
 Low risk of complications and treatment-related
adverse events
 AUAguidelines recommend that parental preference is considered
when choosing an appropriate treatment for VUR

 Success rate is expected to rise further with increased experience and

adaptations to the technique

*Deflux is approved for reflux grades II–IV in children

over 1 year of age
Contraindications
 Non-functional kidney(s)
 Hutch diverticuli
 Duplicated ureters
 Active voiding dysfunction
 Ongoing urinary tract infection

[Deflux package insert USA]

Warnings

 Do not inject Deflux intravascularly

 Injection of Deflux into blood vessels
may cause vascular occlusion

[Deflux package insert USA]

Precautions
 DEFLUX should only be administered by qualified physicians
experienced in the use of a cystoscope and trained in
subureteral injection procedures

 The risks of infection and bleeding are associated with the

cystoscopic procedure used to inject DEFLUX. The usual
precautions associated with cystoscopy (e.g., sterile
technique, proper dilation, etc.) should be followed

 The safety and effectiveness of the use of more than 6 ml of

DEFLUX (3 ml at each ureteral orifice) at the same treatment
session have not been established

 The safety and effectiveness of DEFLUX in the treatment of

children under 1 year of age have not been established
[Deflux package insert USA]
Precautions (cont’d)
 DEFLUX is supplied prefilled in a 1 ml syringe with a luer
lock fitting, and is intended for single use only. Carefully
examine the unit to verify that neither the contents nor the
package has been damaged in shipment. DO NOT USE if
damaged. Immediately return damaged product to Q-Med
AB

 DEFLUX is supplied sterile. Do not re-sterilize, as this may

damage or alter the product

 DEFLUX is supplied in a syringe ready for use. Never mix

DEFLUX with other products

 DEFLUX is stored up to 25°C, and used prior to the

expiration date printed on its label. Do not expose DEFLUX
to either sunlight or freezing, as this may damage or alter
the product. Do not use DEFLUX after its expiration date

[Deflux package insert USA]

 Evolving Concepts in
the Treatment & Management

of Benign Prostatic
Hyperplasia
(BPH)
Table of Contents
 Epidemiology & Definitions
 Evaluation
 Treatment & Management
 BPH & Sexuality
 Conclusions
Epidemiology
& Definitions
 Prevalence of BPH
100 • USA
• England
• Denmark
80 • Austria
• India
% • Japan
Prevalence 60
Microscopic
BPH
40

20

0
15 25 35 45 55 65 75 85

(Oesterling JE. Arch Fam Med 1992;1(2):257-66) Age (years)

 Men Requiring Treatment

25%

(Jacobsen SJ, et al. J Urol 1999;162:1301-6)

 BPH Components

Static Dynamic
Increased glandular Increased
tissue & stroma muscle tone

(Lepor H. Int J Clin Pharmacol Ther Toxicol 1989;27(4):151-5;

McNeal J. Urol Clin North Am 1990;17(3):477-86)
 Lower Urinary Tract Symptoms
(LUTS)

Obstructive Irritative
(voiding) (filling)
• Weak stream • Frequency

• Hesitancy • Nocturia
• Urgency
• Sensation of
incomplete emptying • Urge incontinence
• Intermittent stream
• Prolonged urination

(Barry MJ, et al. J Urol 2000;164:1559-64; Kursh ED. Urology News; clevelandclinic.org;
Ouslander JG. Am J Med Sci 1997;314(4):214-8)
 Quality of Life Index (QoL)
Scale Urinary problems (IPSS)
Never
Terrible 6
Mild
5 4.5 Moderate
4.4 4.3
Severe
4
2.9
3 2.9
2.7

2
1.4
1 1.2 1.2

0.4 0.4
0 0.2
Delighted 50 - 59 60 - 69 70 - 79

Age (years)
(MSAM-7. Global Results.
XVIIth EAU Congress, Birmingham UK, Feb 2002, Sanofi-Synthelabo satellite)
 Consultation for Urinary Symptoms
Urinary problems (IPSS)
100 Mild
90 Moderate
80 74
Severe
70
70 63
60
% Patients50 43
40
34
30
25
20
10 15
5 9
0
50 - 59 60 - 69 70 - 79

Age (years)
(Kirby R. XVIIth EAU Congress, Birmingham UK, Feb 2002, Sanofi-Synthelabo satellite)
 Medication for Urinary Symptoms
5% of men reported having undergone surgery Urinary problems (IPSS)
100 Mild
90 Moderate
80 Severe
70
60
% Men 50 48
44
treated 40
35
30
26
20 20
10 10
0 7
2 4
50 - 59 60 - 69 70 - 79

Age (years)
(MSAM-7. Global Results.
XVIIth EAU Congress, Birmingham UK, Feb 2002, Sanofi-Synthelabo satellite)
Epidemiology & Definitions:
Conclusions

 BPH is a very common problem

 BPH impacts on Quality of Life
 Very few patients are treated
Evaluation
 Evaluation of LUTS
• History
• Physical examination
• IPSS
• Urinalysis
• PSA (highly recommended)

(Roehborn CG. Rev Urol 2001;3(3):139-145,

2001 3(3):139-145, 5th Int Consultation on BPH)
Patient History
• General health
• Dietary & fluid intake
• Urinary symptoms
• Previous surgery
• Previous urinary problems (infections, stones)
• Family history of prostate problems
• Medical review
 Evaluation of Symptoms

International Prostate Symptom

Score(IPSS)
 Internally consistent, reliable
 Easy to use

(Barry MJ. Urol 2001;58(Suppl 6A):25-32; Barry MJ et al. J Urol 1992;148(5):1549-57)

(Barry MJ. Urol 2001;58(Suppl 6A):25-32)
(Barry MJ. Urol 2001;58(Suppl 6A):25-32)
(Barry MJ. Urol 2001;58(Suppl 6A):25-32)
(Barry MJ. Urol 2001;58(Suppl 6A):25-32)
If you were to spend the rest of your life with your urinary condition
just the way they have been during the last week, how would you feel about that?

(Barry MJ. Urol 2001;58(Suppl 6A):25-32)

 Differential Diagnosis
Polyuria Bladder
dysfunction (diabetes)
Myogenic
Cystitis
Extrinsic Neurogenic
pelvic mass

Cystolithiasis
Bladder cancer
Hypertrophy or
stenosis of
BPH bladder neck

Prostate Cancer
Urethral carcinoma
Vesicosphincter Urethritis
dyssynergia Urethral
stricture
Stenosis of
urinary meatus

(Ouslander JG. Am J Med Sci 1997;314(4):214-8; Phimosis

Kasraeian A. www.dcmsonline.org; other references upon request)
 Differential Diagnosis
Bladder
dysfunction (diabetes)

Medications
• Anticholinergics
• Antidepressants
• Decongestants
BPH

Prostate Cancer

Urethral
stricture
Stenosis of
urinary meatus

(Ouslander JG. Am J Med Sci 1997;314(4):214-8;

Kasraeian A. www.dcmsonline.org; other references upon request)
Physical Examination in LUTS

 Abdominal examination
 Genital examination
 Digital rectal examination (DRE)
 Focused neurological examination
Possible Findings on DRE

Symmetrical
Normal Tenderness Enlargement (BPH)

Asymmetry Induration Nodularity

 Prostatic Specific Antigen (PSA)

% Prostate
Cancer

4 10
PSA (ng/mL)
(AUA. Oncology 2000;14(2):267-86)
 PSA Testing – Yes or No?

Pros Cons
 Increases cancer  Substantial false
detection rate positive rate
 May detect cancers  False positives triggers
earlier additional tests
 Inexpensive  False negative rate
 No patient morbidity  Not proven to prolong
survival

(AUA. Oncology 2000;14:267-86;CMQ 1998;www.cmq.org/Prostateang.pdf;CPSM 1995;

www.umanitoba.ca/academic/colleges/cps/guidelines_and_statements/317.html;
Sarkar P,et al. Int J Pharm 2002;238(1-2):1-9;Gander L (HSURC) 2000;www.hsurc.sk.ca)
 Guidelines for Early Detection of
Prostate Cancer

DRE and PSA test

 Increase the early detection of prostate cancer
 Indicated when prostate cancer is suspected

 Indicated in the management of prostate cancer

(CUA 1996;www.cua.org/guidelines/earlydetection.html; CPSM 1995;

www.umanitoba.ca/academic/colleges/cps/guidelines_and_statements/317.html;
CMQ 1998; www.cmq.org/Prostateang.pdf)
Guidelines for PSA Testing
“No Canadian organization currently recommends routine
screening of asymptomatic men for prostate cancer,
regardless of age [due to] lack of evidence that better
health outcomes result from screening.”
(Gander L (HSURC) 2000;www.hsurc.sk.ca)

“Men [considering these tests] should be made aware of

the potential benefits and risks.”
(CUA 1996;www.cua.org/guidelines/earlydetection.html)
 Interpretation of PSA Values,
with Normal DRE

PSA Value Interpretation

0.5 – 2.5 ng/mL Very low risk of cancer
2.5 – 4 ng/mL Low risk of cancer
4 – 10 ng/mL Refer: 24% chance of cancer
> 10 ng/mL Refer: 63% chance of cancer

Rise > 20%/yr Refer

(CMQ 1998, www.cmq.org/Prostateang.pdf; AUA. Oncology 2000;14(2):267-86;

Kirby RS. Prog Clin Biol Res 1994;386:333-43)
 Complications of BPH

Renal Failure

Urinary Urinary Tract

Retention Infections
Bladder Stones
Recurrent
Hematuria

(Jacobsen SJ. Urol 2001; 58(Suppl 6A):5-16;

Nouri M, et al. Ann Urol 1999;33(4):243-51)
Evaluation: Conclusions
 Evaluation is simple
 Majority of patients do not require
a urological evaluation
Treatment &
Management
 Management of BPH in Family
Medicine
Patient must be involved in all decision-
Initial Evaluation making
• History
• Examination
Abnormal
• Urinalysis baseline tests
• PSA recommended

IPSS & QOL

BPH Indications
complications for referral
7 or less 8 or more

No response to
Watchful Consider therapy
Waiting treatment
alternatives
Patients
preferance
(Roehborn CG. Rev Urol 2001;3(3):139-145, 5th Int Consultation on BPH
Gurunadha Rao Tunuguntla HS. Clin Geriat 2002;10(5):20-5)
 Indications for surgical therapy
Complications
Patient must be
involved in all
decision-making

Indications for Failure of drug

surgical therapy
intervention

Patient’s refusal to
receive pharmaco
therapy
Transurethral Resection of Prostate
(TURP)
Resectoscope

Bladder

Prostate

Removal of
Hypertrophied
Tissue
 Impotence & BPH Surgery
OPEN: open surgery
% Patients TURP: transurethral resection of prostate
With impotence 16 TUIP: transurethral incision of prostate
ILC: interstitial laser coagulation
14 TUNA: transurethral needle ablation
TUMT: transurethral microwave thermotherapy
12
10
8
6
4
2
0
OPEN TURP TUIP ILC TUNA TUMT

Surgery type
(Altwein J. XVIIth EAU Congress, Birmingham UK, Feb 2002, Sanofi-Synthelabo satellite)
 Retrograde Ejaculation & BPH
Surgery
OPEN: open surgery
% Patients with
TURP: transurethral resection of prostate
Retrograde ejaculation TUIP: transurethral incision of prostate
100 ILC: interstitial laser coagulation
90 TUNA: transurethral needle ablation
80 TUMT: transurethral microwave thermotherapy
70
60
50
40
30
20
10
0
OPEN TURP TUIP ILC TUNA TUMT

Surgery type
(Altwein J. XVIIth EAU Congress, Birmingham UK, Feb 2002, Sanofi-Synthelabo satellite)
 in Favour of Pharmacologic
Treatment

 Early 1990s:
 Surgical treatment sharply declined
 Due to the advent of medical therapy

 Selective, long-lasting α 1-blockers are

most popular

 Primary-care physicians have a very

active role

(Holtgrewe HL. Urology 1998 Apr;51(4A Suppl):1-7;

Baine WB, et al. J Urol 1998 Sep;160(3 Pt 1):816-20)
 Medical Therapy

5α -reductase α -blockers
inhibitors

Non-selective Uroselective

(Narayan P, et al. Urol 1998;51(Suppl 4A):38-45)

 5a-Reductase Inhibitors
 One agent – finasteride
 Improves LUTS in men with large prostate
(DRE, PSA, TRUS)
 Reduces risk of retention and surgery
 Has long latency period before effect
 Reduces PSA (50% at one year)
 Alters sexual function

(Gurunadha Rao Tunuguntla HS. Clin Geriat 2002;10(5):20-5; Kasraeian A. www.dcmsonline.org; Gormley GJ, et al. NEJM
1992;327:1185-91)
 Finasteride 5mg Daily, 12-months
P values are compared to placebo
22%
30

20

% Change 10
from Baseline
0

-10

-20
-19%
-30 -21%
Prostate Total Peak
Volume Symptom Urinary
P<0.001 Score Flow Rate
P<0.001 P<0.001
(Gormley GJ, et al. NEJM 1992;327(17):1185-91)
 Finasteride – Long-Term Results
 Open extension of the 12-month trial
 3-year follow-up
 Prostate volume continued to decrease
 19 - 26% below baseline at 12 months
 27% below at 36 months
 Flow rates and symptoms continued to improve
 Long-term results are based on a total of 297
men

(Stoner E. Urol 1994;43(3):284-92)

 α -Blockers in BPH
Mechanism of action
• Block
α -adrenoreceptors

• Relax smooth muscle

Ø Ø the α -adrenoreceptor = relax smooth muscle

in the prostate and bladder neck

(Gurunadha Rao Tunuguntla HS. Clin Geriat 2002;10(5):20-5;

De Mey C. Eur Urol 2000;38(Suppl 1):25-39)
α -Adrenoreceptors
α
α 1 α 2

α 1A α 1B α 1D α 2A α 2B α 2C
α 1L
 α -Blockers
 Have rapid onset of action
 Useful in large or small prostates
 Two types:
 Non-Selective
 terazosin
 doxazosin
 Selective
 Tamsulosin (α 1A subtype)
 Alfuzosin (uroselective)

(Hofner K, et al. World J Urol 2002;19:405-12; Roehborn CG. Urol 2001;58(Suppl 6A):
55-64; Gurunadha Rao Tunuguntla HS. Clin Geriat 2002;10(5):20-5)
 Effect of α -Blockers on Flow
 A meta-analysis
 Placebo-controlled studies of 6,333 patients
 Direct comparative studies of α -blockers (alfuzosin, terazosin,
doxazosin and tamsulosin)
 507 patients
 Efficacy defined as % improvement in total symptom score and
peak urinary flow (Qmax)
 All α 1-adrenoceptor antagonists seem to have similar efficacy in
improving symptoms and flow
 General improvement
 Total symptom score by 30-40%
 Qmax by 16-25%

(Djavan B, et al. Eur Urol 1999;36(1):1-13)

 Effect of α -Blockers on Flow*
* Results from 4 clinical trials; dose/regimen is not comparative
** SR = sustained-release formulation 5 mg BID

% Change from baseline Drug Placebo P value

Alfuzosin SR (n=340) +2.4 (29%) +1.1 (14%) 0.006

Terazosin (n=277) +2.2 (23%) +0.8 (8%) 0.03

Doxazosin (n=177) +2.3 +0.1 <0.05

Tamsulosin (n=281) +1.4 (13.1%) +0.4 (3.8%)0.028

(Chapple CR. Br J Urol 1998;81(Suppl 1):34-47)

 Effect of α -Blockers on
Total Symptom Score*
* Results from 4 clinical trials; dose/regimen is not comparative
** SR = sustained-release formulation 5 mg BID

% Change from baseline Drug Placebo P value

Alfuzosin SR** (n=390) -31 18 0.007

Terazosin (n=2084) -38 -18 <0.001

Doxazosin (n=156) -17 -9 <0.01

Tamsulosin (n=288) -35.8 -23.7 0.002

(Chapple CR. Br J Urol 1998;81(Suppl 1):34-47)

XATRAL® Once Daily
Alfuzosin extended-release
Three-layer GEOMATRIX® Tablet

Swelling Eroding

0 Time (h) 20

(Hofner K, et al. World J Urol 2002;19:405-12)

 XATRAL® Delivery System

1. Swelling and slow diffusing

2. Slow constant diffusing
1.
3. Eroding & final dissolution

2. 100

% Dose
50

3.
2 6 12 20

Time (hours)
(Hofner K, et al. World J Urol 2002;19:405-12;
Roehborn CG. Urol 2001;58(Suppl 6A):55-64)
 Pharmacoscintigraphic Study in
Fed vs. Fasted Conditions
14 Fasted

12 Fed

10

Alfuzosin 8
plasma
6
levels (ng/mL)
4

0
2 4 6 8 10 12 14 16 18 20 22 24

Time (hours)
(Roehborn CG. Urol 2001;58(Suppl 6A):55-64)
 XATRAL® Efficacy
IPSS Score 19
Placebo ** PP << 0.01
Alfuzosin *** 0.001
18 10mg OD

17

IPSS score 16

15 *** ***
**
14
0 28 56 84
Time (days)
(Roehborn CG, et al. Urol 2001;58:953-9)
 XATRAL® Efficacy
Peak Urinary
12
Flow Rate
*** ***
11.5

11
10.5
Qmax
(mL/s)
10

9.5 Placebo
Alfuzosin *** P < 0.001
9 10mg OD

0 28 56 84
Time (days)
(Roehborn CG, et al. Urol 2001;58:953-9)
 Occurrence of Orthostatic
Hypotension at Anytime During Treatment

* Decrease on SBP ≥ 20 mmHg, standing compared to supine position

Placebo Alfuzosin
10mg OD

Hypertensive patients
Orthostatic hypotension* 9.3% 1.7%

Overall incidence
Orthostatic hypotension* 4.3% 4.3%

(Roehborn CG, et al. Urol 2001;58:953-9)

 Uroselectivity
Tamsulosin vs. Alfuzosin:
Symptom Score
11.5
Alfuzosin
10.5
2.5mg TID
Tamsulosin
9.5
0.4 mg OD
Mean
8.5
Total
Symptom
Score 7.5

6.5

0 2 6 12
(Buzelin JM, et al. Br J Urol 1997;80:597-605) Time (weeks)
 Uroselectivity
Tamsulosin vs. Alfuzosin: Qmax
12.5

12

11.5

11 Alfuzosin
Mean Qmax 2.5mg TID
(mL/s) 10.5 Tamsulosin
0.4 mg OD
10

0 2 6 12

Time (weeks)
(Buzelin JM, et al. Br J Urol 1997;80:597-605)
 Uroselectivity – α 1A Subtype
Tamsulosin
 Receptor distribution:
 70% α 1A subtype is in prostate,
bladder neck & vas deferens
 Functional impact:
 More effect on urethral pressure
compared to vascular effect

(Roehrborn CG. Urol 2001;58(6 Suppl 1):55-63)

α 1A Uroselectivity
Tamsulosin
 Could be advantageous when considering
cardiovascular side effects
 Could also be a liability when considering
ejaculatory problems
 Uroselectivity without selectivity for α 1A
should be advantageous for ejaculatory
health
 Alfuzosin: Overview
 Alfuzosin shares some structural similarities
with doxazosin, terazosin and prazosin but
not with tamsulosin
 Alfuzosin is metabolized by the liver
 Although alfuzosin does not discriminate
between α 1-adrenoreceptors and has no
α 1-pharmacological selectivity, it has
functional and clinical uroselectivity

(Hofner K, et al. World J Urol 2002;19:405-12;

Roehborn CG. Urol 2001;58(Suppl 6A):55-64)
 Alfuzosin: Overview (cont’d)
 Alfuzosin has been shown to concentrate in the
prostate
 Alfuzosin does not penetrate the
blood/brain barrier

(Roehborn CG. Urol 2001;58(Suppl 6A):55-64;

Martin DJ, et al. Life Sci 1998;63(3):169-76)
 α -Blockers: Overview
 Similar efficacy
 The efficacy remains long-term (5-year data is
currently available)
 The difference between a1-adrenoceptor
blockers is related to the side effect profile
(uroselective agents are better tolerated)
 Alfuzosin and tamsulosin appear to be better
tolerated than doxazosin, terazosin and prazosin

(Roehborn CG. Urol 2001;58(Suppl 6A):55-64)

Treatment & Management:
Conclusions
 Some treatments can negatively impact
sexuality decreasing QoL
 Alfuzosin 10mg OD has few side effects
 Alfuzosin 10mg OD is as effective as other α -
blockers in relieving LUTS due to BPH
The Voiding Continuum
 Potty Training 2
 Bumps along the road 4
 Normal Voiding pattern or sometimes
established dysfunctional voiding
 Overactive Bladder
 It’s my prostate, doc. >50
 The aging bladder >70