ASTHMA DETAILED PHARMACOLOGY & PHARMACOTHERAPEUTICS NOTES
1.
Definition
Asthma is a chronic inflammatory disease of the airways
characterized by:
- Variable and recurrent airflow obstruction
- Bronchial hyperresponsiveness
- Airway inflammation
- Episodes of wheezing, breathlessness, chest
tightness and cough
- Symptoms and airflow limitation that vary over
time and in intensity
Simple
concept
Asthma = Inflamed + Hyperresponsive +
Narrowed airways
The important point is that airway
narrowing is usually variable and reversible, either spontaneously or
with treatment.
2. Normal Airway vs Asthmatic Airway
Normal
airway
Asthmatic
airway
3. Etiology / Causes
Asthma is usually multifactorial.
A.
Genetic factors
A person may inherit a tendency
toward:
- Allergy
- IgE-mediated responses
- Airway hyperresponsiveness
- Atopy
Atopy = genetic tendency to develop allergic diseases such as
asthma, allergic rhinitis and eczema.
B.
Allergic triggers
Common allergens include:
- House dust mites
- Pollen
- Animal dander
- Cockroach allergens
- Mold/fungi
- Certain occupational allergens
These can produce IgE-mediated
airway inflammation.
C.
Respiratory infections
Especially:
- Viral respiratory infections
- Rhinovirus
- Influenza
- Respiratory syncytial virus and others
Respiratory infections can trigger
acute worsening.
D.
Environmental irritants
- Tobacco smoke
- Air pollution
- Dust
- Strong perfumes
- Chemical fumes
- Smoke
- Aerosols
E.
Occupational exposure
Examples:
- Flour dust → baker's asthma
- Latex
- Isocyanates
- Wood dust
- Chemical fumes
- Animal proteins
F.
Drugs
Important drug triggers:
- Aspirin and other NSAIDs in susceptible individuals
- β-blockers
- Some drugs may worsen bronchospasm in susceptible
patients
G.
Exercise
Exercise-induced bronchoconstriction may occur, particularly in poorly controlled asthma.
4. Risk Factors
Patient-related
factors
- Family history
- Atopy
- Allergic rhinitis
- Obesity
- Previous respiratory infections
- Airway hyperresponsiveness
Environmental
factors
- Air pollution
- Tobacco smoke
- Occupational exposure
- Indoor allergens
- Outdoor allergens
- Climate/weather changes
Medication-related
- Aspirin/NSAIDs in susceptible patients
- Non-selective β-blockers
5. Clinical Manifestations
The classical symptoms are:
1.
Wheezing
A musical/whistling sound,
particularly during expiration.
2.
Dyspnea
Difficulty in breathing.
3.
Chest tightness
Patient may describe a feeling of
pressure or tightness in the chest.
4.
Cough
Often:
- Dry
- Worse at night
- Worse early in the morning
- May be the only symptom in some patients
Characteristic
feature
Symptoms are variable and may
worsen:
- At night
- During exercise
- After allergen exposure
- During respiratory infection
- With cold air
- With smoke or pollution
6. Pathophysiology of Asthma
This is one of the most important
pharmacology exam topics.
Step
1 — Trigger exposure
Step
2 — Immune response
Important cells include:
- Mast cells
- Eosinophils
- T lymphocytes
- Dendritic cells
- Macrophages
Important inflammatory mediators
include:
- Histamine
- Leukotrienes
- Prostaglandins
- Cytokines
- Chemokines
Step
3 — Bronchoconstriction
Mediators stimulate bronchial smooth
muscle.
Step
4 — Airway edema
Inflammation causes:
Step
5 — Excess mucus
Goblet cells and mucus glands become
more active.
Step
6 — Airway hyperresponsiveness
Inflamed airways become excessively
sensitive to stimuli.
Therefore, even relatively mild
stimuli can cause:
Bronchoconstriction
7. Airway Remodeling
Repeated or chronic inflammation can
cause structural changes.
Changes
include:
- Smooth-muscle hypertrophy
- Increased mucus glands
- Goblet-cell hyperplasia
- Subepithelial fibrosis
- Thickening of the basement membrane
- Increased vascularity
Consequence
8. Important Asthma Mediators
|
Mediator |
Major effect |
|
Histamine |
Bronchoconstriction, vascular permeability |
|
Leukotrienes C₄/D₄/E₄ |
Powerful bronchoconstriction + mucus secretion +
edema |
|
Prostaglandins |
Modulate bronchial inflammation and tone |
|
Cytokines |
Promote and maintain inflammation |
|
Eosinophil mediators |
Airway epithelial injury and inflammation |
High-yield
point
Cysteinyl leukotrienes are
particularly important bronchoconstrictor mediators.
9. Diagnosis
Asthma should be suspected from the
clinical pattern and confirmed by demonstrating variable expiratory airflow
limitation.
Important
investigations
A.
Spirometry
Important parameters:
- FEV₁ = Forced expiratory volume in first second
- FVC = Forced vital capacity
- FEV₁/FVC ratio
Asthma generally produces an obstructive
pattern.
B.
Bronchodilator reversibility
Spirometry is performed before and
after administration of a bronchodilator.
Improvement in expiratory airflow
supports asthma.
C.
Peak Expiratory Flow Rate — PEFR
Useful for:
- Monitoring disease
- Detecting variability
- Assessing response to treatment
- Patient self-monitoring
D.
Bronchial provocation testing
May be used when asthma is suspected
but routine spirometry is not diagnostic.
Examples:
- Methacholine challenge
- Exercise challenge
E.
Allergy testing
May include:
- Skin-prick testing
- Specific IgE testing
Useful for identifying allergic
triggers.
F.
FeNO
Fractional exhaled nitric oxide (FeNO) can help identify type 2/eosinophilic airway
inflammation in appropriate clinical settings.
10. Classification of Anti-Asthmatic Drugs
A.
Bronchodilators
1.
β₂-adrenergic agonists
Short-acting β₂ agonists (SABA)
- Salbutamol/albuterol
- Terbutaline
Long-acting β₂ agonists (LABA)
- Salmeterol
- Formoterol
2.
Antimuscarinic drugs
Short-acting
- Ipratropium
Long-acting
- Tiotropium
3.
Methylxanthines
- Theophylline
- Aminophylline
B. Anti-inflammatory drugs
1.
Corticosteroids
Inhaled
corticosteroids — ICS
- Budesonide
- Beclometasone
- Fluticasone
- Ciclesonide
- Mometasone
Systemic
corticosteroids
- Prednisolone
- Hydrocortisone
- Methylprednisolone
2.
Leukotriene modifiers
Leukotriene
receptor antagonists
- Montelukast
- Zafirlukast
5-lipoxygenase
inhibitor
- Zileuton
3.
Mast-cell stabilizer
- Cromolyn
C. Biologic drugs
Examples:
- Omalizumab
- Mepolizumab
- Reslizumab
- Benralizumab
- Dupilumab
- Tezepelumab
These are generally reserved for
selected patients with severe asthma despite optimized standard therapy.
11. Mechanism of Action of Important Drugs
A.
β₂-Agonists
Example: Salbutamol
MOA
Easy
memory
β₂ → Gs → cAMP ↑ → Bronchodilation
12. Corticosteroids
Example: Budesonide
Important
point
ICS are the cornerstone of
anti-inflammatory controller therapy for asthma.
They are not primarily rescue
bronchodilators.
13. Leukotriene Receptor Antagonists
Example: Montelukast
Useful particularly in selected
patients with:
- Allergic asthma
- Exercise-induced bronchoconstriction
- Aspirin/NSAID-associated respiratory disease
14. Antimuscarinic Drugs
Example: Ipratropium
High-yield
M₃ blockade → ↓ bronchoconstriction
15. Methylxanthines
Example: Theophylline
It also has anti-inflammatory effects
at therapeutic concentrations.
Important
limitation
Theophylline has a narrow
therapeutic index and significant drug-interaction/toxicity concerns, so
its use is limited.
16. Mast-Cell Stabilizer
Cromolyn
It is mainly a preventive/controller-type
drug, not a rescue drug.
17. Biologics
These are used in selected patients
with severe asthma based on phenotype and biomarkers.
Omalizumab
Anti-IgE monoclonal antibody
Mepolizumab
/ Reslizumab
Target IL-5.
Benralizumab
Targets IL-5 receptor α.
Dupilumab
Blocks signaling through:
IL-4 receptor α
Tezepelumab
Targets TSLP, an
epithelial-derived cytokine involved early in airway inflammation.
18. Reliever vs Controller Therapy
This distinction is extremely
important.
Reliever
Used for rapid relief of
symptoms/bronchoconstriction.
Examples:
- SABA in appropriate treatment settings
- ICS-formoterol when used as reliever in
guideline-based regimens
Controller
Used regularly to reduce airway
inflammation and prevent exacerbations.
Examples:
- ICS
- ICS-LABA
- Leukotriene receptor antagonists in selected
patients
- Biologics in severe asthma
Key
concept
Bronchodilator = opens the airway
Anti-inflammatory controller = treats
the underlying airway inflammation
19. Pharmacotherapeutic Management
Modern asthma treatment is based on severity,
symptom control, exacerbation risk, phenotype, age, inhaler technique,
adherence and patient preferences.
The basic principle is:
Do not rely on bronchodilator-only
treatment; anti-inflammatory therapy is central to asthma management.
20. Stepwise Treatment Concept
A simplified adult/adolescent
framework:
Step
1
For patients with infrequent symptoms:
Low-dose ICS-containing therapy, commonly using as-needed low-dose ICS-formoterol
where guideline-appropriate.
Step
2
As-needed low-dose ICS-formoterol or another appropriate low-dose ICS-containing regimen.
Step
3
Low-dose maintenance ICS-LABA
or an appropriate MART/SMART-type
ICS-formoterol strategy where indicated.
Step
4
Medium-dose ICS-LABA
with specialist assessment and
consideration of additional therapy if uncontrolled.
Step
5
Severe/uncontrolled asthma:
Specialist referral
Consider:
- Phenotyping
- Biologic therapy
- Add-on LAMA
- Other selected therapies
- Minimization of long-term systemic corticosteroid
exposure
Remember
Treatment should be stepped up when
asthma is uncontrolled and stepped down when control is maintained,
after reviewing adherence, inhaler technique, comorbidities and risk factors.
21. Acute Asthma Exacerbation
An exacerbation means acute or
subacute worsening of symptoms and lung function from the patient's usual state.
Common
features
- Increasing breathlessness
- Wheezing
- Cough
- Chest tightness
- Reduced PEFR/FEV₁
22. Management of Acute Exacerbation
Step
1 — Rapid assessment
Assess:
- Severity
- Respiratory rate
- Pulse
- Oxygen saturation
- Ability to speak
- Mental status
- PEFR/FEV₁ when feasible
Step
2 — Rapid bronchodilation
Inhaled short-acting β₂ agonist
Example:
Salbutamol
Repeated administration may be
required according to severity and treatment setting.
Step
3 — Oxygen
Supplemental oxygen is given when
clinically indicated to correct hypoxemia.
Step
4 — Systemic corticosteroid
Example:
Prednisolone
Step
5 — Ipratropium
In moderate-to-severe exacerbations,
inhaled ipratropium may be added to a SABA.
Step
6 — Severe/refractory cases
Hospital-level management may include:
- Repeated or continuous inhaled bronchodilators
- Oxygen
- Systemic corticosteroids
- Ipratropium
- IV magnesium sulfate in selected severe cases
- Close monitoring
Important
Sedatives should generally be avoided
in acute severe asthma because of the risk
of respiratory depression.
23. Inhaled Route — Why Preferred?
For many asthma drugs, inhalation is
preferred because it delivers drug directly to the respiratory tract.
Advantages
- Rapid local action
- Smaller systemic exposure
- Lower systemic adverse effects
- Smaller doses required
Examples
- MDI
- DPI
- Nebulizer
- Soft-mist inhaler
24. Spacer Device
A spacer is particularly useful with a
pressurized metered-dose inhaler (pMDI).
Benefits
- Improves drug delivery
- Reduces oropharyngeal deposition
- Helps patients with poor hand-breath coordination
- Can improve inhaled corticosteroid administration
25. Adverse Drug Reactions
β₂
agonists
Common:
- Tremor
- Palpitations
- Tachycardia
- Headache
- Hypokalemia at higher systemic exposure
Corticosteroids
Inhaled
- Oral candidiasis
- Dysphonia
- Throat irritation
Prevention: rinse mouth after ICS use; proper inhaler technique and
spacer use can help.
Long-term
systemic corticosteroids
- Hyperglycemia
- Hypertension
- Osteoporosis
- Weight gain
- Adrenal suppression
- Cataracts
- Increased infection risk
Theophylline
Toxicity may cause:
- Nausea/vomiting
- Tremor
- Insomnia
- Tachycardia
- Arrhythmias
- Seizures
Montelukast
Generally well tolerated, but neuropsychiatric
adverse effects can occur and should be discussed/monitored.
26. Drug Interactions
β-blockers
Non-selective β-blockers can:
Therefore, they can be problematic in
asthma.
NSAIDs/Aspirin
In susceptible patients:
This is associated with NSAID-exacerbated
respiratory disease (NERD).
Theophylline
Many drugs can alter theophylline
concentrations because of its metabolism and narrow therapeutic index.
Examples include certain:
- Macrolides
- Fluoroquinolones
- CYP enzyme inhibitors/inducers
Therefore, interaction checking is
important.
27. Non-Pharmacological Management
Medication alone is not enough.
Important
measures
- Avoid known triggers where practical
- Stop tobacco exposure
- Reduce occupational exposure when relevant
- Manage allergic rhinitis
- Maintain healthy body weight
- Exercise appropriately
- Vaccination according to recommendations
- Correct inhaler technique
- Improve adherence
- Written asthma action plan
- Regular follow-up
28. Patient Counselling
A pharmacist has a major role.
Teach:
1. Correct inhaler technique
2. Difference between controller and
reliever
3. When to seek emergency care
4. Importance of adherence
5. Rinse mouth after ICS
6. Avoid unnecessary NSAIDs if known
to trigger symptoms
7. Recognize worsening symptoms
29. Asthma Action Plan
Patient should know:
Green
zone
Asthma well controlled.
→ Continue regular treatment.
Yellow
zone
Symptoms increasing.
→ Follow individualized action plan
and seek advice as instructed.
Red
zone
Severe symptoms / marked breathing
difficulty / poor response to reliever.
→ Urgent/emergency medical care.
30. Asthma vs COPD — High-Yield Difference
|
Feature |
Asthma |
COPD |
|
Typical onset |
Often childhood/young age, but any age |
Usually adulthood |
|
Airflow limitation |
Variable, often reversible |
Persistent, incompletely reversible |
|
Symptoms |
Variable |
More persistent |
|
Trigger |
Allergens, exercise, infections, irritants |
Smoking, occupational exposure, pollutants |
|
Inflammation |
Often eosinophilic/type 2 in many phenotypes |
Often neutrophilic/macrophage predominant |
|
Bronchodilator response |
Often significant |
Usually limited/incomplete |
|
Main anti-inflammatory therapy |
ICS important |
ICS only for selected COPD patients |
31. Important Pharmacology Exam Points
Remember
these:
32. Very Important Viva Questions
Q1.
What is asthma?
A chronic inflammatory airway disease
characterized by variable respiratory symptoms and variable expiratory airflow
limitation.
Q2.
What are the classical symptoms?
Wheezing, dyspnea, chest tightness and
cough.
Q3.
Which drug class is the cornerstone of anti-inflammatory controller treatment?
Inhaled corticosteroids.
Q4.
What is the MOA of salbutamol?
β₂ receptor stimulation → Gs →
adenylyl cyclase → ↑cAMP → bronchial smooth-muscle relaxation.
Q5.
Why are corticosteroids used?
To suppress airway inflammation and
reduce airway hyperresponsiveness and exacerbations.
Q6.
What is montelukast?
A cysteinyl leukotriene CysLT₁
receptor antagonist.
Q7.
What is omalizumab?
A monoclonal antibody against IgE,
used in selected severe allergic asthma.
Q8.
Why should non-selective β-blockers be avoided/cautioned?
They can cause bronchoconstriction and
reduce the response to β₂ agonists.
Q9.
Why rinse the mouth after inhaled corticosteroids?
To reduce local adverse effects,
particularly oral candidiasis and dysphonia.
Q10.
What is the role of a spacer?
It improves delivery from a pMDI and
reduces oropharyngeal deposition.
33. One-Line Pathophysiology for Exams
Trigger → immune activation →
inflammatory mediator release → bronchoconstriction + mucosal edema + mucus
hypersecretion → airway narrowing → variable airflow obstruction → wheezing,
cough and dyspnea.
34. One-Line Treatment Concept
Control inflammation with
ICS-containing therapy + relieve bronchoconstriction appropriately + avoid
triggers + correct inhaler technique/adherence + step therapy according to
control and severity.
Final
Memory Trick
ASTHMA = "AIRWAY"