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Asthma medicationsAsthma medications

3. 3

4. Asthma, irrespective of the severity, is
a chronic inflammatory disorder of the airways.
Airway inflammation is associated with:
● Airway hyperresponsiveness
● Airflow limitation
● Respiratory symptoms.
Definition of AsthmaDefinition of Asthma

5. Airway
inflammation
Airflow
obstruction
Bronchial
hyperresponsiveness
SymptomsSymptoms
Asthma Pathophysiology
The tip of the iceberg
Source: Peter J. Barnes, MDSource: Peter J. Barnes, MD

6. 6
o …… in susceptible individuals, inflammatory symptoms
are usually associated with widespread but variable
airflow obstruction and an increase in airway response
to a variety of stimuli.
o Obstruction is often reversible, either spontaneously
or with treatment.
Asthma definition

7. Airway
inflammation
Airflow
obstruction
Bronchial
hyperresponsiveness
SymptomsSymptoms
Asthma Pathophysiology
The tip of the iceberg

8. 8
• Inflammation in asthma patients can be
present during symptom-free periods:
o Symptoms resolve quickly. Inflammation, however, as
measured by airway hyperresponsiveness, takes far
longer time .
o As chronic inflammation causes an increase in airway
hyperresponsiveness, if the inflammation is not
controlled, symptoms are likely to reoccur.

9. 9
Can asthma be cured?
Asthma is an eminently controllable illness. Indeed, for
most sufferers, control is so effective that it amounts to
a virtual cure. But asthma is not curable
Asthma is a long-term disease that has no cure.
The goal of asthma treatment is to control the
disease.

10. 10
Aim of management
Aim of asthma management is to control the disease
Complete Control is defined as
1. No daytime symptoms
2. No night-time awakening due to asthma
3. No need for rescue medication
4. No asthma attacks
5. No limitations on activity including exercise
6. Normal lung function (in practical terms FEV1 and/or
PEF>80% predicted or best)
7. Minimal side effects from medication.

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Underlying principles of management
•Before initiating drug
treatment check
– Compliance with
existing treatment
– Inhaler technique
– Eliminate trigger factors

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Pharmacological management

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Smooth
muscle
dysfunction
Airway
inflammation/
remodelling
r
• Inflammatory cell infiltration/
activation
• Mucosal oedema
• Cellular proliferation
• Epithelial damage
• Basement-membrane thickening
• Bronchoconstriction
• Bronchial hyper-reactivity
• Hyperplasia
• Inflammatory-mediator
release
Symptomsexacerbations
Asthma is a two component disease

15. (ICS)

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Inhaled therapy constitutes the cornerstone
of asthma treatment .

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Not all asthma inhalers are the same

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Controllers
 Inhaled corticosteroids
 Inhaled long-acting b2-
agonists
 leukotrienes modifiers
 Sustained release
theophylline
 Systemic
glucocorticosteroids
 Anti-IgE (Omalizumab)
Relievers
 Inhaled short acting b2-agonists
 Short acting anticholinergics
 Methylxanthines
Medications for Asthma Management

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• The following medicines act as short-acting
bronchodilators:
 Inhaled short-acting β 2
agonists
 Inhaled ipratropium bromide
 β 2
agonist tablets or syrup
 Theophyllines.
• Inhaled SABA works more quickly and/or with
fewer side effects than the alternatives

25. 25

26. 26
• Prescribe an inhaled short-acting β2
agonist as
short term reliever therapy for all patients
with symptomatic asthma.

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30. 30
 Salbutamol is the commonly used inhaled bronchodilator
therapy .
 It is a short- acting ß-2 agonist, has a rapid onset of action
(within five minutes) and usually provides 4–6 hours of
bronchodilation.
 It should be used as a reliever therapy and is in the first
step of all guidelines on asthma management.

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The use of short-acting inhaled beta2-agonists
on a daily basis, or increasing use, indicates
the need for additional long term control
therapy.

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Rescue Medications

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 Oral preparations of beta2 agonists have been used
extensively in the past with children but are less
effective than inhaled preparations and have
more side-effects

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The use of albuterol syrup has fallen out of favor over
the past decade with the advent of better modalities of
targeted, inhaled delivery systems (e.g., MDI with
spacer/holding chamber, nebulizer solution).
• AAAAI Guidelines (2004, p88) prefer inhaled
beta2-agonists to oral because higher
concentrations are delivered more effectively to
the airways, the onset of action is substantially
shorter, and systemic side effects can be
avoided or minimized.
• Authors concluded lack of updated information was a possible reason that
community-based PCPs continued to prescribe syrup.
Special Consideration – Albuterol
Syrup

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 It is important that while reviewing a patient with
asthma, the practitioner establishes how often the
patient needs the reliever therapy.
 Need for frequent bronchodilator therapy, especially for
interval symptoms such as exercise intolerance or night
coughs, may indicate escalation of therapy .

36. 36
 Increasing use of SABA treatment or the use of SABA >
3 doses a week for symptom relief (not prevention of
EIB) generally indicates inadequate asthma control and
the need for initiating or intensifying anti-inflammatory
therapy.
 Regularly scheduled, daily, chronic use of SABA
is not recommended.

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38. 38
 Good asthma control is associated with little or no
need for short-acting β2
agonist.
 Anyone prescribed more than one short acting bronchodilator
inhaler device a month should be identified and have their
asthma assessed urgently and measures taken to improve
asthma control if this is poor.

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40. Beclomethasone
Budesonide
Fluticasone
Inhaled corticosteroids

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• Inhaled corticosteroids are the recommended
& most effective preventer drug for adults
and children with asthma , for achieving overall
treatment goals.

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• There is an increasing body of evidence
demonstrating that, at recommended doses, ICS are
also safe and effective in children under five with
asthma.

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Beclomethasone
Dipropionate 100 ug/dose
Beclomethasone
Dipropionate 50 ug/dose

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 In adults, a reasonable starting dose of inhaled
corticosteroids will usually be 400 micrograms
BDP per day and in children 200 micrograms
BDP per day.
 Titrate the dose of inhaled corticosteroid to the
lowest dose at which effective control of asthma is
maintained

53. 53
Is important that while considering a change of the type of
steroids or inhaler device used (e.g. Turbohaler),
equivalent doses of inhaled steroids relative to
beclometasone are given before the change is initiated to
avoid any inadvertent risk of overdosing with steroids.

54. 54
 BDP and Budesonide are approximately equivalent in clinical
practice, although there may be variations with different delivery
devices.
 At present a 1:1 ratio should be assumed when changing between
BDP and budesonide.
 Fluticasone provides equal clinical activity to BDP& budesonide
at half the dosage
 Mometasone appears to provide equal clinical activity to BDP
and budesonide at half the dosage.
COMPARISON OF INHALED
CORTICOSTEROIDS

55. 55
 Most current ICS are slightly more effective when taken
twice rather than once daily, but may be used once daily
in some patients with milder disease.
 There is little evidence of benefit for dosage frequency
more than twice daily.
 Give inhaled corticosteroids initially twice daily
(except ciclesonide which is given once daily).
Frequency of dosing of inhaled corticosteroids

56. 56
ICS usage as a preventer therapy should be
explained to the parents in simple, plain
terms.

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Pharmacokinetics of Inhaled Drugs

58. Children’s Healthcare of Atlanta
Dose, drug, &Dose, drug, &
route dependentroute dependent
Corticosteroids for Asthma: Benefits and Risks
ReducesReduces
inflammationinflammation
Most effectiveMost effective
long-term controllong-term control
medication formedication for
asthma*asthma*
DecreasesDecreases
morbidity / mortalitymorbidity / mortality
Generally knownGenerally known
and can beand can be
monitoredmonitored
BenefitsBenefits
RisksRisks

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 The safety of ICS is of crucial importance and a balance
between benefits and risks for each individual needs to
be assessed.
 Account should be taken of other topical steroid
therapy (e.g. for eczema) when assessing systemic risk
 Steroid warning cards should be issued to patients on
higher dose inhaled steroids, and at every review,signs of
systemic steroid toxicity should be actively looked for .

60. 60
 Administration of medium or high dose ICS (at or
above 400 micrograms BDP a day or equivalent)
may be associated with systemic side effects(e.g
growth failure and adrenal suppression) .
 Isolated growth failure is not a reliable indicator of adrenal
suppression and monitoring growth cannot be used as a
screening test of adrenal function .

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 Monitor growth (height and weight centile) of
children with asthma on an annual basis.
 The lowest dose of inhaled corticosteroids
compatible with maintaining disease control should be
used.

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In general,while the use of ICS may be associated with
adverse effects (including the potential to reduced bone
mineral density) with careful ICS dose adjustment this
risk is likely to be outweighed by their ability to reduce
the need for multiple bursts of oral corticosteroids .

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1. Oropharyngeal candidiasis
2. Hoarseness
3. Coughing
To reduce the potential for adverse affects:
 Use the lowest dose necessary to maintain control.
 Administer with spacers/holding chambers.
 Advise patients to (Rinse with water , gargle and
spit out) after inhalation.
Local side effects

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 In children, pMDI and spacer are the preferred method of
delivery of β2 agonists or inhaled corticosteroids.
 A face mask is required until the child can breathe
reproducibly using the spacer mouthpiece.
 Where this is ineffective a nebuliser may be required

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Without Spacer
With Spacer

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Aerochamber spacer
Aerochamber spacer with mask

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74. Choosing an inhaler device for children with asthma *
-
Age group Preferred device Alternative device
Younger than 4 years
Pressurized metered-dose
inhaler plus dedicated spacer
with face mask
Nebulizer with face mask
4-5 years
Pressurized metered-dose
inhaler plus dedicated spacer
with mouthpiece
Nebulizer with mouthpiece
Older than 6 years
Dry powder inhaler or
breath actuated pressurized
metered-dose inhaler or
pressurized metered-dose
inhaler with spacer with
Nebulizer with mouthpiece

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 Inhaled medications is a waste of money if not used properly
 Poor technique is a barrier to good control
 Check at each visit
 Don’t rely on patient’s knowledge – ask them to
demonstrate

79. 79
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53

80. 80
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
95%
5%
Schematic representation of potential dose distribution Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Fate of inhaled drugs – Poor Technique

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 Stepping down therapy once asthma is controlled is
recommended , but often not implemented leaving some
patients overtreated.
 Patients should be maintained at the lowest possible
dose of inhaled corticosteroid.
 Reduction in inhaled corticosteroid dose should be slow
as patients deteriorate at different rates.

82. 82
Stepping down therapy
 Reductions should be considered every three months,
decreasing the dose by approximately 25–50% each time.
 Regular review of patients as treatment is stepped down
is important .

83. Treatment Options for adult Patients
Not Controlled on Inhaled Steroids
Patients not controlled on inhaled steroidsPatients not controlled on inhaled steroids Patients not controlled on inhaled steroidsPatients not controlled on inhaled steroids
Increase theIncrease the
dose of inhaleddose of inhaled
steroidsteroid
Add leukotrieneAdd leukotriene
receptor receptor
antagonistsantagonists
Add long-acting
beta2-agonists
Add Add
theophyllinetheophylline

84. 84
LABA’s

85. 85
LABA’s

86. Children’s Healthcare of Atlanta
• Recent data indicating a possible increased risk of
asthma Related death associated with use of LABA in a
small group of individuals has resulted in increased
emphasis on the message that:
• LABA should not be used as monotherapy in asthma &
must only be used in combination with an appropriate
dose of ICS.

87. 87
 Long-acting inhaled β2
agonists should only be started in
patients who are already on inhaled corticosteroids, and
the inhaled corticosteroid should be continued.
 The benefits of these medicines used in conjunction with
ICS in the control of asthma symptoms outweigh any
apparent risks.
SAFETY OF LONG-ACTING Β2
AGONISTS

88. 88
 In clinical practice, however, it is generally considered that
combination inhalers (ICS and LABA) aid adherence and
also have the advantage of guaranteeing that the LABA
is not taken without the ICS

89. Combination Medications
Combination
Medications
ICS LABA
Symbicort®
Budesonide
(Pumicort®)
Formoterol
(Oxeze®)
Seretide®
Fluticasone
(Floxitide®)
Salmeterol
(Severent®)

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105. Children’s Healthcare of Atlanta

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ANTI-IgE MONOCLONAL ANTIBODY
 Omalizumab is a humanised monoclonal antibody which binds
to circulating IgE, reducing levels of free serum IgE.
 In adults and children over 6 years of age, it is licensed in
the UK with the following indication:
patients on high-dose ICS and long-acting β2
agonists
who have impaired lung function, are symptomatic
with frequent asthma attacks, and have allergy as an
important cause of their asthma.

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 Omalizumab is given as a subcutaneous injection every
two or four weeks depending on IgE level and weight.
The total IgE must be <1,300 international units
(IU)/ml for children over 6 years of age.
 In adults and children >12 years, the licensed
indication is a IgE up to 1,500 IU/ml but there is no
published data to support its efficacy and safety above
700 IU/ml.

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 Local skin reactions may occur , Anaphylaxis, presenting
as bronchospasm, hypotension, syncope, urticaria,
and/or angioedema of the throat or tongue has been
reported to occur after administration of omalizumab.
Anaphylaxis has occurred as early as the first dose, but
has also occurred after one year.
 Due to risk of anaphylaxis, omalizumab should only be
administered to patients in a healthcare setting under
direct medical supervision.

118. 118
 Omalizumab given by subcutaneous injection may be
considered in patients with a high steroid burden to
reduce the steroid burden for the patient.
 Omalizumab treatment should only be initiated in
specialist centres with experience of evaluation and
management of patients with severe and difficult
asthma.

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