Uro gynacology- botox

1. Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1

2. Moderators:
Professors:
 Prof. Dr. G. Sivasankar, M.S., M.Ch.,
 Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
 Dr. J. Sivabalan, M.S., M.Ch.,
 Dr. R. Bhargavi, M.S., M.Ch.,
 Dr. S. Raju, M.S., M.Ch.,
 Dr. K. Muthurathinam, M.S., M.Ch.,
 Dr. D. Tamilselvan, M.S., M.Ch.,
 Dr. K. Senthilkumar, M.S., M.Ch.
Dept Of Urology, KMC and GRH, Chennai 2

3. BOTULINUM TOXIN
 Botulinum toxin - produced by bacterium
clostridium botulinum
 Causative agent - Botulism
 Gram positive bacillus, noncapsulated, fastidious,
produce subterminal spores
 Seven antigenically distinct botulinum toxins
- A to G
Dept Of Urology, KMC and GRH, Chennai 3

4.  BoNT - synthesized as single chain POLYPEPTIDE
M.W -150 KD
 Cleaved to form the dichain molecule ( light and
heavy chain) with a disulfide bridge
Dept Of Urology, KMC and GRH, Chennai 4

5.  Light chain - acts as a zinc
endopeptidase with proteolytic activity
located at the N-terminal end
 Heavy chain - provides cholinergic
specificity and responsible for binding the
toxin to presynaptic receptors
 Promotes light-chain translocation
across the endosomal membrane.
Dept Of Urology, KMC and GRH, Chennai 5

6. MECHANISM OF ACTION
 Inhibit acetyl choline release at presynaptic
cholinergic nerve terminal , there by inhibit striated
& smooth muscle contractions
 Ach release from bladder parasympathetic efferent
terminals – primary target of BoNT
 Four steps - Required for toxin induced paralysis
Dept Of Urology, KMC and GRH, Chennai 6

7. Dept Of Urology, KMC and GRH, Chennai 7

8. BINDING OF TOXIN HEAVY CHAIN
TO NERVE TERMINAL RECEPTOR
 Heavy chain of the toxin
- particularly important
for targeting the toxin to
specific types of axon
terminals
 Toxin must get inside
the axon terminals to
cause paralysis
Dept Of Urology, KMC and GRH, Chennai 8

9. Dept Of Urology, KMC and GRH, Chennai 9

10. INTERNALIZATION OF TOXIN
WITHIN NERVE TERMINAL
 Following attachment of
the toxin heavy chain to
proteins on the surface
of axon terminals, the
toxin can be taken into
neurons by endocytosis
Dept Of Urology, KMC and GRH, Chennai 10

11. TRANSLOCATION OF LIGHT CHAIN
INTO CYTOSOL
 Light chain able to cleave endocytotic vesicles and
reach the cytoplasm
 Light chain of the toxin - protease activity.
 Type A toxin proteolytically degrades the SNAP 25
protein a type of SNARE protein
 SNAP-25 protein is required for vesicle fusion that
releases neurotransmitters from the axon endings .
Dept Of Urology, KMC and GRH, Chennai 11

12. Dept Of Urology, KMC and GRH, Chennai 12

13. INHIBIT RELEASE OF NEURO
TRANSMITTER
 Botulinum toxin cleaves SNAREs, prevents
neurosecretory vesicles fusing with the nerve synapse
plasma membrane and releasing their
neurotransmitters
Dept Of Urology, KMC and GRH, Chennai 13

14.  BTX reduce type Ia /II intrafusal muscle fiber afferent
conduction ,
 Affecting spinal stretch reflex
 Decrease muscle tone & contractility without affecting
muscle strength
 Direct effect on detrusor motor innervations
Dept Of Urology, KMC and GRH, Chennai 14

15.  Affect afferent nervous transmission via inhibition
of Ach , ATP, glutamate, nerve growth factor &
substance P
 Modulates intrinsic bladder reflexes, results in
central desensitation, decrease in urgency.
Dept Of Urology, KMC and GRH, Chennai 15

16. SEROTYPES
 Seven serotypes have been isolated
 Antigenically and serologically distinct but structurally
similar.
 Subtype BoTX A and B – most clinically relevant
Dept Of Urology, KMC and GRH, Chennai 16

17. SIDE EFFECTS
 Dysphagia
 Muscle weakness
 Allergic reactions
 Flu like syndrome
 Ptosis
 Injection site reactions
 Respiratory compromise
Dept Of Urology, KMC and GRH, Chennai 17

18. Commercial Preparations
 Botox - onabotulinumtoxinA
(Allergan, Irvine, CA, USA)
 Dysport - abobotulinumtoxinA
(Ipsen Biopharm Ltd,Slough, UK)
 Xeomin - incobotulinumtoxinA
(Merz Pharmaceuticals UK Ltd, Herts, UK)
 Prosigne - Lanzhou Biological Products,
Lanzhou, China
 PurTox - (Mentor Corporation, Madison, WI, USA)
Dept Of Urology, KMC and GRH, Chennai 18

19. USES IN UROLOGY
 Over active bladder
 Detrusor overactivity
 Detrusor sphincter dyssynergia
 Interstitial cystitis
 Benign prostatic hyperplasia
Dept Of Urology, KMC and GRH, Chennai 19

20.  Intrasphincter injection in suprasacral spinal cord
injury
 Chronic abacterial prostatitis
 Children with NDO , urinary incontinence & disorders
refractory to antimuscarnic therapy
Dept Of Urology, KMC and GRH, Chennai 20

21. Overactive bladder
 Symptom complex characterised by urinary
urgency with or without urge urinary incontinence
 Neurogenic OAB– OAB occurs in association with a
known underlying neurogenic pathology ( spinal cord
injury, multiple sclerosis)
 Idiopathic OAB – NO evidence of any identifable
neurologic disorder
Dept Of Urology, KMC and GRH, Chennai 21

22. DOSAGE and CONCENTRATION
 Commonly BTX-A -- 300U
(Range 100- 400u)
 Injected in 30 sites of 10U/ml
( Range – 6.7 -25U/ml)
Dept Of Urology, KMC and GRH, Chennai 22

23. INJECTION TECHNIQUE
 Performed under intravenous sedation or local
anaesthesia
 Prophylatic antibiotic
 Lithotomy position
 21F rigid cystoscope and- collagen injection needle -
create submuscosal bleb under vision
Dept Of Urology, KMC and GRH, Chennai 23

24.  Endoscopic guidance – toxin injected into 15-30 sites
evenly distributed intramural injection including
bladder base and posterolateral walls
 Bladder dome – excluded due to intraperitoneal
perforation & bowel injury
 Trigone – spared to avoid inducing vesicoureteral
reflex
Dept Of Urology, KMC and GRH, Chennai 24

25. Dept Of Urology, KMC and GRH, Chennai 25

26. Evaluation
 Before injecting botulinum Toxin
UTI and other obvious pathology - to be
excluded
 Complete urological evaluation
 Medical history, physical examination
 Bladder diary, urine analysis
 Urine culture, urinary tract ultrasonography
 Urethro-cystoscopy, bladder washing cytology
 Urodynamic investigation
Dept Of Urology, KMC and GRH, Chennai 26

27. INDICATIONS
 Refractory OAB( failure to respond to behavioural
treatment )
 Failed pharmacotherapy with more than one
antimuscarinic for at least 4 weeks
Dept Of Urology, KMC and GRH, Chennai 27

28. PATIENT PREPARATION
 UTI - to be excluded , adequately treated according to
the antibiotic sensitivity
 Avoid aminoglycosides- may potentiate the
neuromuscular blocking effects
 Local anaesthesia - lidocaine gel instilled into the
urethra , exposed for 10 min.
 Lithotomy or supine position - depending on
cystoscope used
Dept Of Urology, KMC and GRH, Chennai 28

29. Surgical Steps  Performed through a rigid
or flexible cystoscope
 Injection needle is
inserted into the working
channel usually after
overview urethro-
cystoscopy.
 Avoids potential urethral
lesions during pushing of
the cystoscope through
the urethra into the
bladder by an injection
needle accidentally
protruding out of the
working channel
Dept Of Urology, KMC and GRH, Chennai 29

30.  Urethro-cystoscopy done –
exclude pathological findings
such as urethral stricture,
bladder neck sclerosis,
urethral,bladder stones, and
bladder tumours
 Addition routinely perform a
bladder washing cytology to
exclude a carcinoma in situ
Dept Of Urology, KMC and GRH, Chennai 30

31.  Urethrocystoscopy-
injection needle is
inserted into the
working channel and
pushed forward upon
appearance in the visual
field
Dept Of Urology, KMC and GRH, Chennai 31

32.  Injecting into
suburothelial layer, a
typical bubble occurs.
Dept Of Urology, KMC and GRH, Chennai 32

33.  Botulinum toxin -usually
injected at 10 – 30
different sites depending
on the dilution and dose
used
 Trigone is traditionally
spared
Dept Of Urology, KMC and GRH, Chennai 33

34.  After the procedure,
relevant bleeding -
excluded by final
cystoscopy.
 Bladder is emptied and
the patient is discharged
home without an
indwelling catheter
Dept Of Urology, KMC and GRH, Chennai 34

35. OUTCOMES
 Provide clinically significant benefit in adults with
neurogenic detrusor overactivity and incontinence
refractory to antimuscarnics
 Improved incontinence episodes
 Antimuscarnic agents could be discontinued in 28%
to 58 %
 Quality of life
Dept Of Urology, KMC and GRH, Chennai 35

36. Urodynamic outcomes
 Significant improvements
Mean cystometric bladder capacity
Mean voiding pressure
Reflex volume
Bladder compliance
Maximum detrusor pressure
Dept Of Urology, KMC and GRH, Chennai 36

37.  Significant response to BoTX seen early as 1week
after treatment
 Maximum effect seen between 1 to 4 week
 Efficacy appears persists - at least 3 -4 months &
upto 1 year
 Repeated injections required for continued
therapeutic effect
Dept Of Urology, KMC and GRH, Chennai 37

38. Neurogenic DO in children
 Most common pathology –
meningomyelocele, spinal cord tumous &
trauma
 BTX – emerged as alternative treatment to bladder
augumentation, NDO refractory to antimuscarnic
treatment
Dept Of Urology, KMC and GRH, Chennai 38

39.  Injection protocol – 30 to 50 inj of 5 to 12 U/kg
 Performed under GA
 similar procedure
 Follow up to 4 to 12 weeks
 Beneficial effects – clinical and urodynamic
parameters in children refractory to conservative
therapies
Dept Of Urology, KMC and GRH, Chennai 39

40. DETRUSOR EXTERNAL SPHINCTER
DYSSYNERGIA (DESD)
 Involuntary contraction of striated external
sphincter during detrusor contractions
 BTX – Urethralsphincteric injection
minimally invasive , decrease sustained high
voiding pressure
 Urethal BTX injections – reduces maximum urethral
pressure , maximum detrusor voiding pressure
Dept Of Urology, KMC and GRH, Chennai 40

41.  Chronic prostatitis/ CPPS –
injections of BoTX directly into prostate
Dept Of Urology, KMC and GRH, Chennai 41

42. Bladder Pain Syndrome
Interstitial cystitis
 As intravesicaL &
intradetrusor
 BoTX - useful in
refractory BPS
Dept Of Urology, KMC and GRH, Chennai 42

43.  BENIGN PROSTATIC HYPERPLASIA - BoNT-A
injection into prostate induced
 atrophy of the prostate by inducing apoptosis
 inhibiting proliferation
 downregulating α1A-adrenergic receptors
Dept Of Urology, KMC and GRH, Chennai 43

44. Suprasacral Spinal Cord Injury
 Complete lesion above the sacral spinal cord
associated
detrusor overactivity,
smooth sphincter synergia and
striated sphincter dyssynergia
 Neurologic examination - show spasticity of
skeletal muscle distal to the lesion,
hyperreflexic deep tendon reflexes
abnormal plantar responses
impairment of superficial and deep sensation
Dept Of Urology, KMC and GRH, Chennai 44

45.  Striated sphincter dyssynergia causes a
functional obstruction with poor emptying and
high detrusor pressure
Rx
Intrasphincteric injection of botulinum toxin
- lower the detrusor leak point
Dept Of Urology, KMC and GRH, Chennai 45

46. THANK YOU
THANK YOU
Dept Of Urology, KMC and GRH, Chennai 46