Role of Mirabegron in Treating Overacting Bladder.

Its a medical educational topics.

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ROLE OF MIRABEGRON IN TREATING OAB.
Presented by
Dr. Poly Begum
Assistant Professor
Diabetic Association Medical College
Faridpur.

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ROLE OF MIRABEGRON IN TREATING OAB

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Definition
Urinary incontinence is defined as objectively
demonstrable involuntary loss of urine so as to
cause hygienic and/ or social inconvenience for
day to day activity.
An overactive bladder is defined by the
international Continence Society as “on that is
shown objectively to contract spontaneously or on
provocation during the filling phase while the
patient is attempting to inhibit micturation.”

5. Epidemiology
Among the elderly women, OAB is the
commonest cause of urinary incontinence.
Overall prevalence is 12-15% in women aged
40 years or more.
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8. Impact on quality of life
significantly impaired
■Social
–Reduction in social interaction/increased social
isolation
–Cessation of some hobbies
■Physical
–Limitations or cessation of physical activities
■Sexual
–Avoidance of sexual contact
■Psychological
–Guilt/depression
–Fear of:
» Being a burdenOr Having urine odor


Occupational
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9. Physical Problems
Limitations or cessation of
physical activities.
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10. Psychological Problems
Guilt/ depression Fear of:
Being a burden Or
Having urine odor.
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11. Social Problems
Reduction in social
interaction/increased
social isolation.
Cessation of some
hobbies.
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12. Sexual Problems
•Avoidance of
sexual contact.
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13. Occupational/Financial
Problems
•Absence from work
•Job loss
•Change of job
•Poor relationship with
employers/ employee
•Financial loss
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14. Vicious Circle of
Bladder Control Problems
Isolation
Deppression
Guilt
Social, domestic,
physical, sexual
and psychological
problems
Absence
from work
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15. Causes
1.Majority: Idiopathic unknown.
2.Psychosomatic
3. Some:±neurological deficit.
•Multiple sclerosis
•Stroke
1.Parkinson’s Disease
2.Spina Bifida
3.Spinal cord damage
4. Following surgery for incontinence
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The patho-physiology is obscure.
There may be increased alpha-adrenergic activities causing
increased detrusor contraction.
The identical situation occurs in initiating an event of normal
micturation- relaxation of urethral sphincter mechanism followed
by contraction of detrusor muscle.
There is inappropriate detrusor contraction results when there is
passage of urine into the proximal urethra due to incompetence of
the bladder neck. Due to detrusor activity incontinence occur.
Pathophysiology

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This occurs despite the effort of the individual
to inhibit them.
Other explanation is change in the detrusor
smooth muscle property (due to Atherosclerosis
or Neuropathy) that leads to inappropriate
detrusor overactivity.
The involuntery contraction occurs at any
bladder volume.

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19. Diagnosis
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20. * Survey conducted by Gallup Group (European Study).
A Hidden Condition*
■Many:
Self-manage:
voiding frequently, reducing fluid intake, wearing
pads
■Two-thirds:
symptomatic for 2 ys before seeking treatment
■30% who seek treatment: receive no
assessment
80% not examined
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21. Urge Incontinence
•Sudden & involuntary
loss of urine
FFrreqequuenencycy
88 oorr momorree vviissiittss tto tthhee
ttoiillett//2244 hh UUririnnaattiionn aatt nniighhtt
•• 22 orr momorere vviissiittss tto ttoiillett
dduuririnng sslleeeeppiinngg hhoouursrs
Frequency
•8 or more visits to the toilet/24 h
Nocturia Urination at night
•2 or more visits to toilet
during sleeping hours
Symptoms
UUrrggenncy
SSuuddddenn,
ssttroronng
ddessiirere tto
uuririnnaattee
Urgency
•Sudden, strong
desire to urinate
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OAB

22. Diagnosis of OAB
A.History and symptom assessment for exclusion of stress
incontinence
B.Physical Examination
Perform general, abdominal ( Including bladder palpation) and
neurological examination look for -
Perineal sensation
Pelvic muscle tone & bulbocavernous to reflex to known the integrity of
sacral reflex (S
2-9
)
Perform Pelvic Examination
Cranial nerve examination
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23. Diagnosis of OAB
C.Investigation
Urine R/M/E and C/S-
Before urodynamic procedure due to avoid flure up to infection
To rule out hematuria , Pyuria, Bacteriuria, Glycosuria, Proteinuria
USG of L/A
To exclude any pelvic mass
Maintenance of frequency volume chart.
Urodynamic-
* Uroflowmetary - In idiopathic- flow rate high and the voiding time
short.
* Cystometry - Urge to pass urine is provocated at a much lower bladder
filling of 100-175ml of water.
-True detrusor pressure increase.
* Cystourethroscopy - To exclude local associated pathology
Findings are usually normal bladder capacity reduced.
* Vediocystourethregraply - May reveal bladder trabeculation
diverticulac, vesicoureteric reflex.
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24. Differential Diagnosis :
OAB and Stress Incontinence
Medical History and Physical Examination
Symptom Assessment
Symptoms
Urgency (strong, sudden desire to void)
Frequency with urgency (>8 times/24 h)
Leaking during physical activity; eg,
coughing, sneezing, lifting
Waking to pass urine at night



Overactive
bladder
Stress incontinence
Yes No
Yes

No


No

Yes



Large

(if present)

Small


Often no Yes

Usually

Seldom

Ability to reach the toilet in time
following an urge to void
Amount of urinary leakage with
each episode of incontinence
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25. Management
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General Management
Conservative Management
Surgical Management

26. Barriers to Treatment
■Patient misconceptions and fears:
“Part of normal aging or everyday life” “Not
severe or frequent enough to treat” “Too
embarrassing to discuss” “Treatment won't
help”
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27. Treatment Options
I.Life style changes
II.Behavioral therapy
III. Medication
IV. Minimally invasive
therapies Botulinum A-toxin
Neuromodulation
V.Surgery
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28. I. Lifestyle changes
Moderate fluid intake
Reduce or eliminate caffeine
Avoid fluids before bed
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29. II. Behavioral Therapy
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30. Bladder Training:
•Helps patients regain control of their bladder by
teaching them to resist the urge to pass urine
•Helps to increase bladder capacity and reduce
the number of episodes of incontinence.
-delayed/timed voiding
-urge suppression exercises
•Effective but requires a high degree of
motivation and commitment from patients.
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31. Pelvic Floor Exercises
Repeat, as
recommended
by physician
1. Locate pelvic floor
muscles
Squeeze pelvic floor
muscles as tightly
as possible for a few
seconds (maximum
of 10 sec)
Relax completely for
at least 10 seconds
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33. III. Medications
■Anticholinergic Agents
1.Trospium chloride (Spasmex)
2.Oxybutynin (Ditropan)
Oxybutynin transdermal (Oxytrol)
•Tolterodine (Detrol)
1.Solifenacin (Vesicare)
2.Darifenacin (Enablex)
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34. Spasmex
l asr
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36. Onset of action
Rudy D. BJU International. 2006;97:540-546.
Week 2 Week 4 Week 6 Week 8 Week 10 Week 12
Trospium chlpride has looked to onset of action in the first week
OXYBUTININ VS. TOLTERODINE
SOLIFENACIN
DARIFENACIN
TOLDERODINE
Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7
TROSPIUM
TROSPIUM
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37. Side Effects
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38. 1. Trospium Chloride
■Quaternary amine as opposed to
tertiary amine
■20 mg BID dose
■No pass through blood/brain barrier
with less side effects
■Rapid onset
■Not metabolized by liver
■60% excreted in the urine unchanged
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39. 2. Oxybutynin
Previous standard of treatment for urge
incontinence
Effectively reduces symptoms
High incidence of dry mouth severe enough to
cause discontinuation
Reported to cause CNS adverse events and
cognitive dysfunction
Katz IR et al. Am J Geriatr Soc. 1998;46:8-13.
Donnellon CA et al. BMJ. 1997;315:1363-1364.
Yarker YE et al. Drugs and Aging. 1995;6:243-262.10/14/17 Dr. Poly Begum 39

40. 3. Tolterodine
■Immediate: 2 mg.
long acting LA 4 mg dosing
■Side effects: similar to oxybutynin
■Develop a potent and pure muscarinic
receptor antagonist
■Equipotent to oxybutynin on the bladder
■Less potent than oxybutynin on
glands/salivation
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41. 4. Solifenacin)
■5 – 10 mg daily dose
■Side effects: dry mouth, constipation
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42. 5. Darifenacin
■M
3 selective anticholinergic
■7.5 mg or 15 mg once a day
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43. Side Effects of Anti-muscarinic
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Anti-muscarinic block the muscarinic receptors in
the bladder wall and therefore inhibit abnormal
detrusor contraction in the bladder.
The effect of these agents are not selective for the
bladder but also affect the salivary gland, intestine
and eye.

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Discontinuation rates of OAB therapyDiscontinuation rates of OAB therapy

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Newer agent for OAB


β
3
adrenergic agonist
MIRABEGRON
Pharmacology
β
3
adrenergic agonist - Agonizes β
3
receptor of the
bladder detrussor muscle leading to relaxation.

46. •Mirabegron is now available in Bangladesh
Newer agent for OAB
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47. Mode of action of Mirabegron
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48. Dosage Administration of Mirabegron
The recommended starting dose is 25 mg once daily, with or
without food 25 mg is effective within 8 week. Based on
individual efficacy and tolerability, may increase dose to 50
mg once daily.
•Patients with Severe Renal Impairment or Patients with
Moderate Hepatic Impairment : Maximum dose is 25 mg once
daily
•Patients with End Stage Renal Disease (ESRD) or Patients with
Severe Hepatic Impairment : Not recommended
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Increase blood pressure
Common cold symptoms
Dry mouth
UTI
Urinary retention
Costipation
Headache
Fatigue or drowsiness
Side Effect of
Mirabegron

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Benefits of Mirabegron-
Convenient once daily dosing.
It has better side effects profile.
Significantly reduced number of nocturia
episodes.
Significantly reduces number of incontinence
episodes.
Significantly reduces urinary frequency
number.

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52. IV. Minimally invasive therapies
1. Botox
®
injection
•100 units diluted in 10ml saline in 30 injection sites,
sparing the trigone
•Under local anesthesia (xylocaine 2% in 20ml, 20
minutes)
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53. 2. Sacral
Retention.
Neuromodulation
Implantation of programmable
stimulator SC which delivers
low amplitude electrical
stimulation via a lead to the
sacral nerve, usually accessed
via the S3 foramen.
FDA has approved InterStim
Therapy, by Medtronic, as a
safe sacral nerve stimulator for
treatment of Urinary Urge
Incontinence, Urinary
Frequency, and Urinary
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54. V. Surgery
 All measures: failed.
 Cystoplasty
a portion of the bowel is attached to the
bladder to increase its capacity
A
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