Asthma

yitayih kefale

(B.pharm, MSC, clinical pharmacist)

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 Definitions
• Asthma is a chronic inflammatory
disorder of the airways in which many
cells and cellular elements play a role: in
particular;
 mast cells, eosinophil's, T lymphocytes,
macrophages, neutrophils, and epithelial cells.

• This causes obstructive airway disease

which is known as bronchial asthma.
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• Physiologic manifestation: Air Way
narrowing which is usually reversible
• Relieved spontaneously or with
Bronchodilator ± Corticosteroids.
• Clinical manifestations: a triad of
paroxysms of cough, dyspnea and
wheezing

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 Disease pattern

• Episodic --- acute exacerbations

interspersed with symptom free periods.

• Chronic --- daily Airway obstruction

which may be mild, moderate or severe ±
superimposed acute exacerbations

• Life-threatening--- slow-onset or fast-

onset (fatal within 2 hours)
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Airflow limitation in asthma is because of
• Broncho constriction: airway narrowing and a
subsequent interference with airflow
• Airway edema: mucus hypersecretion and leakage of
some vascular contents
• Airway hyper responsiveness: an exaggerated
broncho constrictor response to a wide variety of
stimuli
• Airway remodeling: Permanent structural changes
can occur in the airway
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 Triggers of acute asthmatic
episodes
• Allergens • Drugs
• Occupational – Aspirin
exposures – NSAIDS
– Cyclooxygenase-2
• Viral respiratory
inhibitors (in aspirin-
tract infections sensitive asthma
• Exercise patients)
• Emotions – Antiadrenergic and
cholingeric drugs
• Exposure to
• Preservatives
irritants
– Tartazine, Sulfites,
• Environmental benzalkonium chloride
exposures

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 Clinical presentations
Wheezing Symptoms occur or
History of any of the worsen in the
following: presences of:
Coughing (worse Exercise
particularly at nights) Viral infection
Recurrent wheeze Inhalant allergen
Recurrent difficultly
Irritants
breathing
Changes in weather
Recurrent chest tightness
Strong emotional
Symptoms occur or
expression
worsen at night, Stress
awakening the patient Menstrual cycles
and seasonal

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 Diagnosis
• Detail medical history, Signs and symptoms

• Pulmonary function tests using Spirometry

– Demonstrate obstruction and assess reversibility in patients ≥ 5
years
– Forced vital capacity(FVC), forced expiratory volume in 1
second(FEV1), FEV1/FVC and peak expiratory flow rate(PEFR)
– Ratio of the forced expiratory volume in 1 second (FEV1) over
forced vital capacity is reviewed to determine if obstruction is
present.

• Biomarkers of inflammation

• Peak flow meter

– used mostly for monitoring of asthma treatment effectiveness
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– Not reliable test for diagnosis because of high patients variability14
 Goals of therapy
• Reduce impairment
– Prevent chronic and troublesome symptoms (e.g., coughing
or breathlessness in the daytime, in the night, or after
exertion).
– Require infrequent use (≤2 days a week) of inhaled SABA
for quick relief of symptoms (not including prevention of
exercise-induced bronchospasm [EIB]).
– Maintain (near) normal pulmonary function.
– Maintain normal activity levels (including exercise and
other physical activity and attendance at school or work).
– Meet patients’ and families’ expectations of and satisfaction
with asthma care.
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 Goals of therapy
• Reduce risk
– Prevent recurrent exacerbations of asthma
and minimize the need for ED visits or
hospitalizations.
– Prevent loss of lung function; for children,
prevent reduced lung growth.
– Provide optimal pharmacotherapy with
minimal or no adverse effects of therapy.

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 Asthma management
• Asthma is incurable but highly manageable
condition
• 4 components of asthma management
 Routine assessment and monitoring
 Patient education to create a partnership between
clinician and patient
 Controlling environmental factors (trigger factors)
and co morbid conditions that contribute to
asthma severity
 Pharmacologic therapy

• Management is guided by levels of asthma

severity
– Determines regimen selection
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 Classifications of asthma severity

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 Classification of Severity
CLASSIFY SEVERITY
Clinical Features Before Treatment

Symptoms Nocturnal FEV1 or PEF

Symptoms
STEP 4 Continuous <60% predicted
Severe Limited physical Frequent
Persistent activity

STEP 3 Daily 60 - 80% predicted

Attacks affect activity > 1 time week
Moderate
Persistent
STEP 2 >80% predicted
> 1 time a week > 2 times a month
Mild
Persistent but < 1 time a day

< 1 time a week >80% predicted

STEP 1
Asymptomatic and < 2 times a month
Mild normal PEF
Intermittent between attacks

The presence of one feature of severity is

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Asthma in that category. 19
 Nonpharmacologic
management
• Humidified oxygen
• Intravenous fluids
• Environmental control
• Asthma education
• Vaccines (influenza virus, polyvalent
pneumococcals)

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 Stepwise Approach for Managing Asthma in
Children 0 – 4 years

SABA: inhaled short-acting beta2-agonist; ICS: inhaled corticosteroid; LABA: inhaled long-
acting beta2-agonist
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 Stepwise Approach for Managing Asthma in
Children 5 – 11 years

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 Stepwise Approach for Managing Asthma in
ages ≥ 12 years and Adults

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 Asthma treatment ladder

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• Regimen selection is based on severity

• After this, the levels of control should be assessed

and step down and step up therapy should be
done
– Adequately controlled
Step down treatment

– Partially controlled and uncontrolled

Step up therapy

• The goals of therapy are to achieve and maintain

adequate control
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 Levels of asthma control:
should done every clinic visits and preferably for every 4
weeks
helps for stepping up or dawn the treatment to achieve the
control

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 Asthma medications
• Long-term
• Quick-relief
asthma
asthma medications
medications – Oral and
– Systemic inhalational
corticosteroids
corticosteroids – Inhaled long-acting
– Short-acting beta2 beta2 agonist
– Cromolyn/
agonist Nedocromil
– Anticholinergics – Leukotriene
modulators
– Methylxanthine
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 1. Corticosteroids
• MOA: corticosteroids block late reaction to allergen
and reduce airway hyper-responsiveness.
• They inhibit cytokine production, adhesion protein
activation and inflammatory cell migration and
activation.
• Route of administration (systemic, intravenous, oral or
inhaled) is determined by the condition of the patient.
• S/e: facial flushing, appetite stimulation, GI irritation,
headache, mood changes, acne exacerbation, weight
gain, hyperglycemia, leukocytosis, hypokalemia

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 Systemic Corticosteroids
• Used for rapid response during an exacerbation

• Improves pulmonary function within 1-3 hr

• Maximum effect is not achieved until 6 -9 hours or

longer after administration.
• Patients should receive regular ophthalmological
evaluations and osteoporosis screening and
preventative therapy (Ca2+, Vitamin D) if indicated.
• Caution: in patients who have diabetes, hypertension,
adrenal suppression, congestive heart failure, PUD,
osteoporosis, candidiasis and glaucoma.
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 Inhaled corticosteroids

• Indicated for chronic treatment of asthma

• Local AEs: hoarseness and fungal
infection of the mouth and throat.
 Can be decreased through mouth
rinsing, use of a spacer, and use of
certain inhaled steroid products
(Pulmicort Flexhaler® and
beclomethasone (Qvar®)
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 2. Beta2-adrenergic agonists
Relieve bronchoconstriction during acute asthma
exacerbations as well as during chronic therapy and
prevent exacerbations from occurring during
exercise.

MOA: stimulate beta2 receptors, activating adenyl

cyclase, which increase intracellular production of

cAMP resulting in bronchodilation.
AEs: tremor, palpitations, tachycardia, nervousness,
headache, hypokalemia and tachyphylaxis
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 Beta2-adrenergic agonists
• Short-acting beta2 agonist
– Albuterol, levalbuterol, pirbuterol
– Reserved for worsening symptoms, treatment
of acute exacerbations and prophylaxis of
exercise-induced bronchospasm (EIB).
• Long-acting beta2 agonist
– Salmeterol, formoterol
– Used for maintenance treatment of moderate
and severe persistent asthma in combination
with inhaled corticosteriods, prophylaxis of EIB
and in patients with concurrent COPD
– Regimens must include a short-acting agent for
the treatment of acute symptoms and also
include a ICS unless when used to prevent EIB

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 Beta2-adrenergic agonists

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 3. Leukotriene Modifiers
• Used in the prevention of • Zileuton
allergen induced – MOA: blocks the effect of
bronchoconstriction 5-lipo-oxygenase and
• Montelukast, Zafirlukast ultimately blocks
– MOA: leukotriene receptor leukotriene production.
antagonists that prevent – AEs: headache, abdominal
pain, asthenia, nausea,
leukotrienes from
dyspepsia and myalgia
interacting with their – Precaution: hepatic
receptors impairment, alcoholism
– Monitor: liver dysfunction,
– AEs: headache, dizziness, if ALT > 5 times upper
dyspepsia, nausea, limit of normal:
discontinue
diarrhea
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 4. Mast cell stabilizers
 Cromolyn sodium (Intal®) and nedocromil sodium (Tilade®)

 Used to prevent the early and late response of asthma and as

maintenance therapy to suppress nonspecific airway reactivity.
 MOA: act locally by stabilizing mast cells and thereby
inhibiting mast cell degranulation
 Dose
Cromolyn sodium: MDI (0.8mg/puff): 2 puffs QID; nebulizer
(20mg/ampule): 1 ampule QID
Nedocromil sodium: MDI (1.75mg/puff): 2 puffs QID

 Not effective during an acute asthma exacerbation

 AEs: wheezing, coughing, nasal congestion and irritation or

dryness of the throat.
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 5. Methylxanthines
• Theophylline (Uniphyl®)
• Considered when beta-agonists and
corticosteroids fail to control acute asthma
exacerbations and as an alternative to LABA in
persistent asthma
• MOA: inhibits phosdiesterase resulting in increased
levels of cAMP
• Dose: 10mg/kg/day up to 300 mg maximum

• AEs: nausea, vomiting, diarrhea, anorexia,

palpitations, insomnia, seizures and reduced control
of GERD
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 Theophylline: Therapeutic Drug
Monitoring

Theophylline is a narrow therapeutic

window drug.
Therapeutic effect is achieved and toxicity
is minimized by keeping drug
concentrations at 5 – 15 mcg/mL
Signs of toxicity: Tachycardia, headache,
vomiting, seizures, arrhythmias
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 6. Anticholinergics
Ipratropium bromide (Atrovent®), Ipratropium + albuterol
(Combivent®)
MOA: block postganglionic muscarinic receptors in the airway
leading to reduced intrinsic vagal tone to the airways
Dose:
Atrovent: 2 puffs of the MDI every 6 hours; 0.25 mg nebulizer
solution every 6 hours
Combivent: 2 puffs of the MDI every 6 hours; 3 mL nebulizer
solution every 6 hours

AEs: Drying of mouth and respiratory secretions, increased

wheezing in some individuals, blurred vision if sprayed in eyes.

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 7. Immunomodulators
• Omalizumab (Xolair®)
• Used in moderate and severe asthma in patients who
are poorly controlled with conventional therapy
• MOA: attaches to free circulating IgE to prevent it
from binding to mast cells thus inhibiting part of the
inflammatory process.
• Dose: 150-375 mg SC every 2 – 4 weeks
• AEs: injection site reaction
• Black Box Warning(BBW): Anaphylaxis
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 Special Populations

• Exercise-Induced Bronchospasm (EIB)

– Warm-up period may be helpful in preventing
EIB
– Can be prevented with one of the following
options:
• SABA: at least 15 minutes before exercise may be helpful for 2 – 3
hours; drug of choice
• LABA: 30 – 60 minutes before exercise
• Cromolyn sodium and nedocromil: at least 10 minutes
before exercise, duration 1-2 hours
• Montelukast: ≥ 2 hours before exercise
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• Pregnancy

– Monitor the level of asthma control and

lung function during prenatal visits.
– Albuterol is the preferred SABA.

– Inhaled corticosteroids are the preferred

long-term control medication. Budesonide
is the preferred ICS and has pregnancy
category B designation
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 Types of asthma devices
• Inhalers are small, handheld devices that
deliver a puff of medicine into the airways
• Two basic types: metered-dose inhalers
(MDIs) and dry powder inhalers (DPIs).
– MDIs contain a liquid medication delivered as
an aerosol spray. You can place the
mouthpiece 1 to 2 inches from your mouth and
breathe in slowly as you press down on the
inhaler.
– use a spacer (a hollow plastic tube between
the mouthpiece and the canister of medicine)
– The medication is release by propellant
– Shaking is required before use
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 Inhaler devices

STANDARD INHALER DEVICE (SPACER WITH MASK)

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 These are the general steps for using a
metered dose inhaler
1. Remove the cap from the metered dose inhaler.

2. Shake the inhaler for a few seconds.

3. Place your index finger on top of the canister and thumb on the bottom of
the mouthpiece.
4. Tilt your head back slightly and breathe out.

5. Hold the inhaler upright about the width of two fingers from your mouth.

6. Breathe in and out slowly through your mouth one time.

7. Press down on the inhaler as you breathe in as slowly and deeply as you can
- about 3 to 5 seconds.
8. If possible, hold your breath for at least 10 seconds.

9. If more than one puff is required, wait about 1 minute and repeat steps 2-8.

10.Replace the cap on the metered dose inhaler.

11.Gargle and rinse your mouth with water or mouthwash (usually advised only
for steroid-type inhalers)
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 A DPI is similar, but it releases a puff of dry
powder instead of a liquid mist.
 a spacer is not required
 Instead, close your mouth tightly around the
mouthpiece of the DPI inhaler and inhale rapidly
 Never shake and breathing to the medication
will remove some of the medication
 Deep breath is required to release the
medication
 Nebulizers are machines that convert a liquid
medicine into a mist that you inhale into your
lungs.
 Not portable
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 Suggested steps for using Diskus DPI
1) Check dose counter
2) Open using thumb grip
3) Holding horizontally, load dose by sliding lever
until it clicks
4) Breathe out gently away from mouthpiece
5) Place mouthpiece in mouth and seal lips
6) Breathe in steadily and deeply
7) Hold breath for about 10 seconds or as long as
comfortable
8) While holding breath, remove inhaler from
mouth
9) Breathe out gently away from mouthpiece
10)If an extra dose is needed, repeat steps 3 to 9
11)Close
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cover to click shut
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 Summary

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