Asthma

Paroxysmal attacks of Dyspnoea

.,accompanied by wheezing
Asthma
 Asthma
• Triggers
– Allergens
– Exercise
– Respiratory infections
– Drugs and food additives
– Nose and sinus problems
– GERD
– Emotional stress
 Asthma
• Reversible inflammation & obstruction
• Intermittent attacks
• Sudden onset
• Varies from person to person
• Severity can vary from shortness of breath to
death
 Asthma: Pathophysiology
 Swelling of mucus membranes
(edema)
 Spasm of smooth muscle in
bronchioles
Increased airway resistance
 Increased mucus gland secretion
 Asthma: Pathophysiology
Early phase response: 30 – 60 minutes 
Allergen or irritant activates mast cells 
Inflammatory mediators are released 
histamine, bradykinin, leukotrienes, prostaglandins, platelet- 
activating-factor, chemotactic factors, cytokines
Intense inflammation occurs 
Bronchial smooth muscle constricts 
Increased vasodilation and permeability 
Epithelial damage
Bronchospasm 
Increased mucus secretion
Edema
 Asthma: Early Clinical Manifestations
• Wheezing
• Chest tightness
• Dyspnea
• Cough
• Prolonged expiratory phase
 Asthma: Pathophysiology
 Late phase response: 5 – 6 hours
Characterized by inflammation
Eosinophils and neutrophils infiltrate
Mediators are released mast cells release
histamine and additional mediators
Self-perpetuating cycle
Lymphocytes and monocytes invade as well
Future attacks may be worse because of increased
airway reactivity that results from late phase response
Individual becomes hyperresponsive to specific allergens and
non-specific irritants such as cold air and dust
Specific triggers can be difficult to identify and less stimulation
is required to produce a reaction
Asthma: Early Clinical Manifestations

 Expiratory & inspiratory wheezing

 Dry or moist non-productive cough
 Chest tightness
 Dyspnea
 Anxious &Agitated
 Prolonged expiratory phase
 Increased respiratory & heart rate
 Decreased PEFR
Asthma: Severe Clinical Manifestations
 Hypoxia
 Confusion
 Increased heart rate & blood pressure
 Respiratory rate up to 40/minute & pursed lip
breathing
 Use of accessory muscles
 Diaphoresis & pallor
 Cyanotic nail beds
 Flaring nostrils
 Classifications of Asthma
• Mild intermittent
• Mild persistent
• Moderate persistent
• Severe persistent
 Treatment of Asthma
• Drugs which are used for the
treatment of Asthma include:
– Bronchodilators
– Corticosteroids
– Cromoglycates
– Leukotriene receptor antagonists
– Antihistamines
– Expectorants

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 Bronchodilators
• Drugs used to relieve bronchospasms
associated with respiratory disorders
• Includes:
– Adrenoceptor agonists
• Selective β2-agonists & other adrenoceptor agonists
– Antimuscarinic bronchodilators
– Xanthine derivatives

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 Bronchodilators (Cont’d)

• Adrenoceptor agonists
– (i) Selective beta2 agonists(Salbutamol,Terbutaline,Formoterol,Salmeterol)
• Stimulate beta2 receptors in smooth muscle of the
lung, promoting bronchodilation, and thereby
relieving bronchospasms

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 Bronchodilators (Cont’d)

• Adverse effects
– Tachycardia
and
palpitations
– Headache
– Tremor

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 Bronchodilators (Cont’d)
– (ii) Other adrenoceptor agonists
• Less suitable & less safe for use as bronchodilators
because they are more likely to cause arrhythmias &
other side effects
– Ephedrine

• Adrenaline (epinephrine) injection is used in the

emergency treatment of acute allergic and anaphylactic
reactions

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 Bronchodilators (Cont’d)
• Antimuscarinic
bronchodilators(Ipratropium
,Tiotropium):
– Blocks the action of acetylcholine in
bronchial smooth muscle, this reduces
intracellular GMP, a bronchoconstrictive
substance
– Used for maintenance therapy of
bronchoconstriction associated with chronic
bronchitis & emphysema

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 Bronchodilators (Cont’d)

• Adverse effects:
– Dry mouth
– Nausea
– Constipation
– Headache

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 Bronchodilators (Cont’d)
• Xanthine
Derivatives(Theophylline,Aminophylline)
– Main xanthine used clinically is theophylline
– Theophylline is a bronchodilator which relaxes smooth
muscle of the bronchi, it is used for reversible airway
obstruction
– One proposed mechanism of action is that it acts by
inhibiting phosphodiesterase, thereby increasing cAMP,
leading to bronchodialtion

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 Bronchodilators (Cont’d)
– Adverse effects:
• Toxicity is related to theophyline levels (usually 5-15
µg/ml)
• 20-25 µg/ml : Nausea, vomiting, diarrhea, insomnia,
restlessness
• >30 µg/ml : Serious adverse effects including
dysrhythmias, convulsions, cardiovascular collapse
which may result in death

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 Corticosteroids
(Beclomethasone, Budesonide,
Fluticasone)
 Used for prophylaxis of chronic asthma
 Suppressing inflammation
 Decrease synthesis & release of inflammatory mediators
 Decrease infiltration & activity of inflammatory cells
 Decrease edema of the airway mucosa
 Decrease airway mucus production
 Increase the number of bronchial beta2 receptors &
their responsiveness to beta2 agonists

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 Corticosteroids (Cont’d)
• Adverse effects
– Inhaled corticosteroids:
• Candidiasis of the mouth or throat
• Hoarseness
• Can slow growth in children
• Adrenal suppression may occur in long-term, high dose
therapy
• Increases the risk of cataracts

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 Cromoglycates
• Stabilise mast cells & prevent the release of
bronchoconstrictive & inflammatory
substances when mast cells are confronted
with allergens & other stimuli
• Only for prophylaxis of acute asthma attacks

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 Leukotriene receptor antagonists
• Act by suppressing the effects of leukotrienes,
compounds that promote bronchoconstriction
as well as eosinophil infiltration, mucus
productions, & airway edema
• Help to prevent acute asthma attacks induced
by allergens & other stimuli
• Indicated for long-term treatment of asthma

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 Leukotriene receptor antagonists
(Cont’d)
• Adverse effects:
– GI disturbances
– Hypersensitivity reactions
– Restlessness & headache
– Upper respiratory tract infection
– Manufacturer advises to avoid these drugs in pregnancy &
breast-feeding unless essential

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 Management of Chronic Asthma for adults &
schoolchildren above 5yrs (Cont’d)

• Stepping down:
– Review treatment every 3 months
– If symptoms controlled, may initiate stepwise reduction
• Lowest possible dose oral corticosteroid
• Gradual reduction of dose of inhaled
corticosteroid to the lowest dose which
controls asthma

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