Transcript ICS

‫ ميريانا البيضة‬.‫د‬
Pharmacologic Treatment Of
Asthma
1
There are both short-term
and long-term therapeutic
objectives
for every asthmatic patient
2
short-term objectives
are the control of
immediate symptoms
3
Long-term objectives
are those directed at disease
prevention to avoid serious
exacerbations
4
5
Reliever Medications
Shor t-Acting inhaled
β2-Agonists(SABA)
Anticholinergics
6
• Controller Medications
 Inhaled gluCocor ticoSter oids (ICS)
 Leukotriene Modifier s (LM)
 Theophylline (THEO)
 Long-Acting inhaled β2-Agonists
(LABA)
 Systemic GlucoCor ticoSter oids
(SGCS)
7
Pharmacologic
Therapy
(Staging)
Routine Monitoring
(Symptoms & Lung
Function)
Successful Asthma
Management
Prevention
(Trigger factors comorbid conditions)
Patient education
(create a partnership
Between Clinician &
patient)
8
Pharmacologic
Therapy
(Staging)
Routine Monitoring
(Symptoms & Lung
Function)
Successful Asthma
Management
Prevention
(Trigger factors comorbid conditions)
Patient education
(create a partnership
Between Clinician &
patient)
9
Initial Evaluation to classify Asthma Severity
Treating for 4-6 weeks to achieve control
Total evaluation after treatment to identify the
Level of Control
Treatment Modification : Step up or Step down
10
Initial Evaluation to
classify Asthma Severity
Assessment of asthma severity using
symptoms and PEF in
patients presenting for the First Time on No Treatment
11
Classification of Severity
12
CLASSIFY SEVERITY
Clinical Features Before Treatment
Symptoms
STEP 4
Continuous
Severe
Persistent
Limited physical
activity
STEP 3
Moderate
Daily
Attacks affect activity
Nocturnal
Symptoms
Frequent
> 1 time week
FEV1 or PEF
 60% predicted
Variability > 30%
60 - 80% predicted
Variability > 30%
Persistent
STEP 2
Mild
Persistent
> 1 time a week
but < 1 time a day
> 2 times a
month
< 1 time a week
STEP 1
Intermittent
Asymptomatic and
normal PEF between
attacks
 2 times a
month
 80% predicted
Variability 20 30%
 80% predicted
Variability < 20%
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Treating for 4-6 weeks to
achieve control
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TREATMENT STEPS
REDUCE
INCREASE
STEP
STEP
STEP
STEP
STEP
1
2
3
4
5
• Asthma Education
• Environmental Control
• As needed rapid-acting inhaled
B2-agonist
15
16
REDUCE
INCREASE
Treatment steps
Step 1
Step 2
Step 3
Asthma education
As-needed rapid-acting B2agonist
Select one
Controller
options
Low-dose
inhaled ICS
Leukotriene
modifier
Step 4
Step 5
Environmental control
As-needed rapid-acting B2-agonist
Select one
Add one or
more
Add one or
both
Low-dose ICS
plus long-acting
B2-agonist
Medium-or highdose ICS plus
long-acting B2agonist
Oral
glucocorticoste
roid (lowest
dose)
Medium-or
high-dose ICS
Leukotrien
Low-dose ICS plus e modifier
leukotriene
modifier
Low-dose ICS plus
sustained release
theophylline
Sustained
release
theophylline
Anti-IgE
treatment
REDUCE
INCREASE
Treatment steps
Step 1
Step 2
Step 3
Step 4
Step 5
Asthma education
Environmental control
As-needed rapid-acting
2-agonist
Controller options
As-needed rapid-acting 2-agonist
Select one
Select one
Low-dose inhaled ICS
Low-dose ICS plus
long-acting
2-agonist
Leukotriene modifier
Medium-or high-dose
ICS
Leukotriene modifier
Low-dose ICS plus
leukotriene modifier
Sustained release
theophylline
Low-dose ICS plus
sustained release
theophylline
Add one or more
Add one or both
Medium-or high-dose
Oral glucocorticosteroid
ICS plus long-acting 2(lowest dose)
agonist
Anti-IgE treatment
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As needed Short-acting inhaled
B2-agonist (SABA)
Indicated in all age groups
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Preferred
Low-dose ICS
Alternative
Montelukast
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Low-dose ICS
Preferred
LABA
+
Or
Montelukast
Or
SR-Theo
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Medium- dose ICS
OR
High – dose ICS
Step 3
Moderate & Severe Asthma
children 0- 4 years of age
Medium-dose ICS
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Step 4
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Moderate & Severe
Asthma
Medium -dose ICS plus LABA
High-dose ICS plus LABA
Montelukast
+/-
SR-Theo
Step 4
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Moderate & Severe
Asthma
• children 0- 4 years of age
Medium-dose ICS
+
Montelukast
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Step 5
Severe Asthma
Medium dose ICS plus LABA
High-dose ICS plus LABA
+
Montelukast
SR-Theo
+/Oral
Glucocorticosteroids
low dose
Anti-IgE
26
Total evaluation after treatment
to identify the Level of Control
Total Asthma control
Normal Lung Function
Better Quality of life
Non Exacerbation
27
Better Quality of life
28
Better Quality of life
29
Better Quality of life
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Better Quality of life
31
Better Quality of life
32
Levels of Asthma Control
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Characteristic
Controlled
Partly controlled
(All of the following)
(Any present in any
week)
Daytime symptoms
None (2 or less /
week)
More than
twice / week
Limitations of
activities
None
Any
Nocturnal symptoms
/ awakening
None
Any
Need for rescue /
“reliever” treatment
None (2 or less /
week)
More than
twice / week
Lung function
(PEF or FEV1)
Normal
< 80% predicted or
personal best (if
known) on any day
Exacerbation
None
One or more / year
Uncontrolled
3 or more features of
partly controlled
asthma present in any
week
1 in any week
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Treatment Modification :
Step up or Step down
5
4
3
of Treatment
Step up after
4-6 weeks
2
3-6 months
1
Step down After
STEPSTEP STEP STEP STEP
36
Of Treatment
LEVEL OF CONTROL
TREATMENT ACTION
Controlled
Maintain and find lowest
controlling step
Partly controlled
Consider stepping up to
gain control
Uncontrolled
Step up until controlled
Exacerbation
Treat as exacerbation
REDUCE
INCREASE
Treatment steps
Step 1
Step 2
Step 3
Step 4
Step 5
Stepping Down
Treatment When
Asthma Is
Controlled
Regular use of treatment in practice:
stepping down
Treatment steps
Step 1
Step 2
Step 3
Step 4
Select one
Select one
Add one or more
Medium-or high-dose
Low-dose ICS plus ICS plus long-acting 2Low-dose inhaled ICS long-acting 2-agonist
agonist
Controller options
Leukotriene modifier
Medium-or high-dose
ICS
Leukotriene modifier
Low-dose ICS plus
leukotriene modifier
Sustained release
theophylline
Low-dose ICS plus
sustained release
theophylline
Step 5
Add one or both
Oral
glucocorticosteroid
(lowest dose)
Anti-IgE treatment
LABA + ICS (H)
LABA + ICS (M)
LABA + ICS (L)
Stop LABA / ICS (L) once daily
Controllers
(Leukotriene
modifier
or SR Theophylline)
+
ICS (H)
Controllers + ICS (M)
Controllers + ICS (L)
Stop Controllers / ICS (L) once daily
Medications
Airway
Inflammation
ICS
Systemic
Steroids
Leukotriene
modifiers
Cromolyn and
nedocromil
Airway
Obstruction
LABA
Anticholinergic
SABA
Airway
Remodelling
ICS
Theophylline
Corticosteroids
Corticosteroids are the most useful
antiinflammatory agents
Corticosteroids are available for
Oral
Parenteral
and inhaled use
Inhaled gluCocorticoSteroids (ICS)
Inhaled glucocorticosteroids are the most
effective controller therapy in all ages
Evidence A
in Long Term asthma Management
ICS
are safe and effective treatment for
moderate- to-severe asthma
The longterm use of ICS has been associated
with a good safety profile
Side Effects
Hypophyseal
Pituitary
adrenal axis
suppression
Local adverse
effects
Hoarseness
Dysphonia
Cough
oral candidiasis
• High doses ICS (eg, 1,000
μg/d)
• can usually be avoided by the
use of a spacer or holding
chamber and by rinsing the
mouth after each use
Oral preparations (prednisone)
are useful for the treatment of acute
exacerbations of asthma
that are unresponsive to bronchodilator
therapy
Doses of 40 to 60 mg/d are administered
until the patient responds
and then the dosage can be slowly tapered
down
IV corticosteroids
(methylprednisolone, 60 to 80 mg every 6 to 8
h for 1 or 2 days)
preventing further progression of the
severe asthma exacerbation
That
requires hospitalization
Side Effects
Osteoporosis
Cataracts
diabetes mellitus
depression of
immunity to infection
Leukotriene Modifiers (LM)
LT pathway modifiers (LPMs)
are also medications that are considered to be
asthma controllers
Evidence A
in Long Term asthma Management
These agents have been shown to be effective
in preventing allergic rhinitis
Prevention of exercise-induced
bronchospasm
• Adolescents 15 years and Adults: 10 mg at least 2 hours
prior to exercise
• Additional doses should not be administered within 24
hours
Montelukast
DOSING
6 months to 5 years
4 mg/day
6-14 years
5 mg/day
Adolescents >14
years and Adults
10 mg/day
Short-Acting inhaled β2-Agonists
(SABA)
Evidence A
Relief bronchospasm during acute
exacerbations of asthma
Pretreatment of exercise-induced
bronchoconstriction
Short-Acting inhaled β2-Agonists
(SABA)
Treatment should be taken as needed in
controlled asthma
Regular SABA Increased risk of:
• Exacerbation
• Hospital admission in children
Short-Acting inhaled β2-Agonists
(SABA)
The need for regularly scheduled doses of
SABAs
should alert the physician to
the need for more intense
antiinflammatory medication
Long-Acting inhaled β2-Agonists
(LABA)
Evidence A
in Long Term asthma Management in children,
adolescents and adults:
• Control of chronic symptoms
• Prevent nocturnal symptoms
• Exercise-induced bronchoconstriction
Long-Acting inhaled β2-Agonists
(LABA)
The effect of (LABA) has not yet been
adequately studied in infants 5 years and
younger
Long-Acting inhaled β2-Agonists LABA
Salmeterol
Formoterol
> 4 years
old
Inhalation
50 mcg / 12
hours
> 5 years
old
Inhalation
12 mcg / 12
hours
Formoterol (Pharmacodynamics)
Onset
Peak effect
Duration
Within 3 minutes
80% of peak effect within 15
minutes
Improvement in FEV1
observed for 12 hours in
most patients
ombination Strategy Rational
Better control
Synergy
ICS
+
LABA
Better lung
function
Better QOL
Anticholinergics
produce bronchodilatation by
reducing vagal tone
Anticholinergics
In Acute Asthma
Reliever medication but less effective than
SABA
substitute bronchodilator when side effects
preclude the use of β2-agonist
Not recommended for long-term
management of asthma in children
Anticholinergics
The combination between
SABA & Anticholinergics
• Significant Improvement in pulmonary
function
• Significantly reduces the risk of hospital
admission
Medications
Airway
Inflammation
ICS
Systemic
Steroids
Leukotriene
modifiers
Cromolyn and
nedocromil
Airway
Obstruction
LABA
Anticholinergic
SABA
Airway
Remodelling
ICS
Theophylline
Theophylline
Theophylline is an effective bronchodilator
and has antiinflammatory properties
Evidence B
in Long Term asthma Management in
children, adolescents and adults
Theophylline
The side effects are more pronounced
20 to 30 μg/mL
GI side effects
8 to 15 μg/Ml
therapeutic
blood levels in excess of
this range
Serious cardiac
arrhythmias and
seizures
Anti-IgE therapy in Allergic Diseases
IMMUNOMODULATORY AGENTS
(Anti IgE )
Omalizumab Xolair® is a:
IgG monoclonal antibody (recombinant
DNA-derived)
Xolair® FDA approved
for subcutaneous use in severe asthmatics
incomplete symptom control with inhaled
corticosteroid treatment
• Subcutaneous
injection under
medical supervision
• 150 mg – 375 mg
every 2- 4 weeks
Side Effects
Anaphylaxis
• one in 1000 patients
urticarial skin
rash
• 1 % of patients
Mild injection
site reactions
• occur in 44 %
ANTI-IgE THERAPY IN OTHER
DISEASES
•
•
•
•
•
Allergic Rhinitis
Atopic Dermatitis
Food Allergy
Chronic Urticaria
Churg-strauss
Syndrome
Important limits of clinical use
• Individuals must be
12 years of age or
older
Omalizumab in allergic asthma
 Exacerbations 
 Symptoms 
 On-demand medication 
 Steroid-sparing
 Quality of life 
 Lung function ()
 Side effects 