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Receptors (Irritant receptors)
Located in:
Larynx
Trachea
Bronchi
Also present in pleura, ear canal (Arnold reflex)
Stimulated by:
Mechanical → dust, foreign body
Chemical → smoke, gases
Afferent pathway
Mainly via vagus nerve
Carries impulses to cough center
Cough center
Located in medulla (brainstem)
Integrates incoming signals
Coordinates motor response
Efferent pathway
Via:
Phrenic nerve
Spinal motor nerves
To:
Diaphragm
Intercostal muscles
Abdominal muscles
Final response
Deep inspiration → glottis closure → sudden opening
→ explosive expulsion of air (cough)
Dry cough (Non-productive)
No sputum
Irritative
Seen in:
Viral infections
ACE inhibitor use
Indication for antitussives
Productive cough
With sputum
Seen in:
Bronchitis
Pneumonia
COPD
Cough should NOT be suppressed
Upper respiratory infections
Bronchitis
Pneumonia
Asthma
COPD
GERD
Acid reflux → vagal stimulation
Cardiac
Congestive heart failure (pulmonary congestion)
ACE inhibitors (VERY IMPORTANT)
Due to ↑ bradykinin
Dry persistent cough
Clears:
Secretions
Foreign particles
Microorganisms
Excessive cough leads to:
Fatigue
Sleep disturbance
Rib fractures (elderly)
Syncope (rare)
| Feature | Dry Cough | Productive Cough |
|---|---|---|
| Sputum | Absent | Present |
| Nature | Irritative | Clearing |
| Common causes | Viral, ACE inhibitors | Infection, COPD |
| Treatment | Antitussives | Expectorants/mucolytics |
| Suppression | Indicated | Contraindicated |
Receptor stimulation
→ Vagus nerve (afferent)
→ Medullary cough center
→ Motor nerves (efferent)
→ Respiratory muscles
→ Cough
Demonstrates:
Sensory receptor distribution
Vagus nerve pathway
Medullary integration
Clinical importance
Damage to vagus → impaired cough
CNS lesions → abnormal cough reflex
Cough reflex is vagus-mediated protective reflex
Dry cough → treat with antitussives
Productive cough → do NOT suppress
ACE inhibitors → common exam cause of chronic cough
Medulla = central control center
Codeine
Pholcodine
Dextromethorphan
Noscapine
Levodropropizine
Benzonatate
| Class | Drugs | Key Feature |
|---|---|---|
| Central opioid | Codeine, Pholcodine | Strong cough suppression, sedation |
| Central non-opioid | Dextromethorphan, Noscapine | Safer, less addiction |
| Peripheral | Levodropropizine, Benzonatate | No CNS depression |
Antitussives
→ Central acting
→ Opioid
→ Non-opioid
→ Peripheral acting
Suppress medullary cough center
Reduce sensitivity to afferent impulses
Raise cough threshold
Codeine
μ-opioid receptor agonist
Direct depression of cough center
Dextromethorphan
NMDA receptor antagonist
No analgesic action
Minimal respiratory depression
Inhibit sensory nerve endings in respiratory tract
Reduce receptor activation
Decrease afferent impulses
Levodropropizine
Inhibits peripheral cough receptors
Minimal CNS effects
Benzonatate
Local anesthetic action
Blocks stretch receptors in airways
| Type | Site of Action | Mechanism | Key Advantage |
|---|---|---|---|
| Central | Medulla | Suppresses cough center | Strong effect |
| Peripheral | Airway receptors | Inhibits sensory input | No sedation |
| Dextromethorphan | CNS | NMDA blockade | Safer alternative |
Shows:
Central suppression at medulla
Peripheral receptor blockade
Clinical importance
Central drugs → more potent but sedative
Peripheral drugs → safer in children
Antitussives classified into central and peripheral
Codeine → most effective but addictive
Dextromethorphan → safest commonly used drug
Peripheral drugs → no CNS depression
Mechanism:
Central → suppress cough center
Peripheral → block airway receptors
Suppression of cough reflex
↓ sensitivity of cough center
↑ threshold for cough initiation
Sedation (mainly opioids)
Seen with Codeine
CNS depressant effect
May cause:
Drowsiness
Reduced alertness
No improvement in sputum clearance (IMPORTANT CONCEPT)
Antitussives do NOT remove secretions
Can lead to:
Retention of sputum
Worsening of infection
👉 Hence:
Contraindicated in productive cough
| Action | Mechanism | Clinical Relevance |
|---|---|---|
| Cough suppression | Central/peripheral inhibition | Useful in dry cough |
| Sedation | CNS depression (opioids) | May impair alertness |
| No mucus clearance | No effect on secretions | Harmful in productive cough |
Stimulus
→ Reduced receptor signaling / central suppression
→ Increased cough threshold
→ Decreased cough frequency
Mostly well absorbed orally
Rapid onset of action
Widely distributed
CNS penetration (central drugs)
Hepatic metabolism
CYP enzyme involvement
Example:
Codeine → converted to morphine (CYP2D6)
Mainly renal
Varies among drugs:
Short acting → frequent dosing
Long acting → sustained relief
| Parameter | Feature |
|---|---|
| Route | Oral (most common) |
| Metabolism | Hepatic (CYP enzymes) |
| CNS entry | Present in central drugs |
| Duration | Variable |
Oral intake
→ Absorption
→ Liver metabolism
→ CNS / airway action
→ Renal excretion
Class: Opioid antitussive
Mechanism: μ-receptor agonist → suppress cough center
Dose: 10–20 mg orally
Duration: 4–6 hours
Most effective antitussive
Causes:
Sedation
Constipation
Respiratory depression
Risk of dependence
Controlled drug
Class: Non-opioid central antitussive
Mechanism: NMDA receptor antagonism
No analgesic action
Minimal respiratory depression
Safer than opioids
Most commonly used OTC antitussive
Class: Non-narcotic antitussive
Minimal sedation
No addiction potential
Acts centrally (not via opioid receptors)
Class: Peripheral antitussive
Inhibits sensory nerve endings in airway
No CNS depression
Safer in children
| Drug | Type | Mechanism | Sedation | Abuse Risk |
|---|---|---|---|---|
| Codeine | Opioid | μ-receptor | High | High |
| Dextromethorphan | Non-opioid | NMDA block | Low | Low |
| Noscapine | Non-narcotic | Central | Minimal | None |
| Levodropropizine | Peripheral | Receptor inhibition | None | None |
Shows:
Opioid receptor action (codeine)
NMDA blockade (dextromethorphan)
Clinical importance
Codeine → potent but addictive
Dextromethorphan → safer alternative
Antitussives suppress cough reflex but do NOT clear sputum
Codeine = most effective but addictive
Dextromethorphan = safest widely used
Peripheral drugs → no sedation
Hepatic metabolism → important for drug interactions
Common with opioid antitussives
Seen prominently with Codeine
Mechanism:
CNS depression
👉 Clinical relevance:
Impaired alertness
Avoid in:
Drivers
Machinery operators
Due to ↓ gastrointestinal motility
Opioid-induced effect
👉 Chronic use may lead to:
Severe constipation
Bowel dysfunction
Dose-dependent
Seen with opioids
👉 Mechanism:
Depression of respiratory center in medulla
👉 High-risk groups:
Children
Elderly
Patients with lung disease
Mainly with opioids
👉 Features:
Psychological dependence
Tolerance with prolonged use
👉 Important drug:
Codeine
Nausea and vomiting
Dizziness
Allergic reactions (rare)
CNS excitation (high-dose Dextromethorphan)
| Effect | Cause | Common Drug |
|---|---|---|
| Sedation | CNS depression | Codeine |
| Constipation | ↓ GI motility | Codeine |
| Respiratory depression | Medullary suppression | Codeine |
| Dependence | Opioid action | Codeine |
| CNS excitation | High dose | Dextromethorphan |
Opioid action
→ CNS depression
→ Sedation + respiratory depression
→ Chronic use
→ Dependence
Demonstrates:
CNS depression
Respiratory suppression
Clinical importance
Overdose → life-threatening
Requires urgent management
Non-productive cough
Irritative cough
👉 Common causes:
Viral infections
Allergic cough
Drug-induced (ACE inhibitors)
Antitussives should NOT be used
👉 Reason:
Suppression of cough →
↓ sputum clearance →
↑ infection risk
Nocturnal cough → useful (improves sleep)
Post-infectious dry cough
Palliative care (severe cough distress)
| Condition | Role of Antitussives |
|---|---|
| Dry cough | Indicated |
| Productive cough | Contraindicated |
| Nocturnal cough | Useful |
| Chronic cough | Selective use |
Dry cough → suppress
Productive cough → do NOT suppress
Shows:
Absence vs presence of sputum
Airway clearance
Clinical importance
Guides drug selection
Prevents inappropriate use of antitussives
Opioids → sedation + constipation + respiratory depression + dependence
Codeine = most important for adverse effects
Dextromethorphan safer but high dose → CNS effects
Antitussives indicated only in dry cough
Never suppress productive cough (exam favorite concept)
Antitussive + Antihistamine + Decongestant
Antitussive → suppress cough
Antihistamine → reduce allergy/post-nasal drip
Decongestant → relieve nasal congestion
Antitussive:
Dextromethorphan
Antihistamine:
Chlorpheniramine
Decongestant:
Phenylephrine
Dry cough + allergy + nasal congestion
Symptom-based short-term therapy
Productive cough → secretion retention
Unnecessary multi-drug exposure
Fixed-dose combinations without clear indication
Easily available without prescription
Risk of:
Overdose
Drug interactions
Pediatric toxicity
👉 Common problem:
Parents giving cough syrups indiscriminately
| Feature | Rational | Irrational |
|---|---|---|
| Indication | Symptom-specific | Non-specific use |
| Cough type | Dry cough | Productive cough |
| Drug selection | Targeted | Unnecessary combinations |
| Safety | Safer | Increased adverse effects |
Combination drugs
→ Multiple mechanisms
→ Better symptom relief (selected cases)
BUT
→ ↑ adverse effects if irrational
Shows:
Multi-drug composition
Different targets
Clinical importance
Helps in rational prescribing
Prevents misuse
Example:
Chlorpheniramine
Block H1 receptors
Reduce:
Histamine-mediated irritation
Nasal secretions
Common in:
Allergic rhinitis
Mechanism:
Secretions drip into throat → trigger cough
👉 Antihistamines reduce this trigger
First-generation drugs cross BBB
Cause:
Sedation
Night-time relief
👉 Useful in:
Nocturnal cough
Not useful in:
Pure productive cough
Side effects:
Drowsiness
Anticholinergic effects
| Feature | Effect |
|---|---|
| Mechanism | H1 receptor blockade |
| Main use | Post-nasal drip cough |
| Additional benefit | Sedation |
| Limitation | Not useful in productive cough |
Shows:
Nasal secretions → throat
Triggering cough reflex
Clinical importance
Explains antihistamine use
Examples:
Honey
Glycerin
Form protective coating on mucosa
Reduce irritation
Decrease cough reflex
Local soothing action
Increase salivation
Provide symptomatic relief
Moistens airway
Helps loosen secretions
Provides relief in:
Mild cough
Upper respiratory infections
Useful in:
Mild cough
Irritative throat conditions
Safe in:
Children
Pregnancy
| Feature | Demulcents | Antitussives |
|---|---|---|
| Action | Local soothing | Central/peripheral suppression |
| Safety | Very safe | Drug-related risks |
| Use | Mild cough | Moderate-severe dry cough |
Shows:
Protective mucosal layer
Reduced irritation
Clinical importance
Simple and safe therapy
Often first-line in mild cough
Combination cough syrups → rational only in selected cases
OTC misuse → major clinical problem
Antihistamines → best for post-nasal drip cough
Demulcents → safe symptomatic relief
Always differentiate:
Drug therapy vs supportive therapy
Used in productive cough
Aim:
Facilitate expulsion of sputum
Improve mucociliary clearance
Do NOT suppress cough reflex → enhance clearance
Increase bronchial secretions
Reduce viscosity indirectly
Guaifenesin
Ammonium chloride
Directly reduce mucus viscosity
Break structure of mucus
Bromhexine
Ambroxol
Acetylcysteine
Improve mucociliary transport
Enhance movement of mucus toward pharynx
| Class | Mechanism | Drugs |
|---|---|---|
| Expectorants | ↑ secretion | Guaifenesin, Ammonium chloride |
| Mucolytics | ↓ viscosity | Bromhexine, Ambroxol, Acetylcysteine |
| Mucokinetics | ↑ clearance | (Indirect action drugs) |
Thick mucus
→ Mucolytics → ↓ viscosity
→ Expectorants → ↑ secretion
→ Mucokinetics → ↑ movement
→ Easier expectoration
Shows:
Cilia movement
Mucus transport pathway
Clinical importance
Basis of therapy in productive cough
Explains role of mucokinetics
Expectorants → increase secretion
Mucolytics → reduce viscosity (MOST IMPORTANT)
Mucokinetics → improve clearance
Used in:
Productive cough
COPD
Bronchiectasis
Never use antitussives with thick sputum (exam concept)
Drugs:
Guaifenesin
Ammonium chloride
Mechanism:
Reflex stimulation of bronchial glands
↑ watery secretions
👉 Effect:
Dilution of thick mucus
Easier expectoration
Drugs:
Bromhexine
Ambroxol
Mechanism:
Depolymerization of mucopolysaccharides
↓ mucus thickness
👉 Effect:
Converts thick mucus → thinner secretion
Drug:
Acetylcysteine
Mechanism:
Breaks –S–S– bonds in mucoproteins
👉 Result:
Rapid reduction in mucus viscosity
Strong mucolytic action
Thick viscous mucus
→ Expectorants → ↑ fluid secretion
→ Mucolytics → ↓ viscosity
→ Disulfide bond breakdown
→ Thin, mobile mucus
| Class | Mechanism | Result |
|---|---|---|
| Expectorants | ↑ bronchial secretion | Dilution of mucus |
| Mucolytics | Depolymerization | ↓ viscosity |
| Acetylcysteine | Breaks disulfide bonds | Strong liquefaction |
Mechanism:
Reduced viscosity
Enhanced ciliary movement
👉 Outcome:
Efficient transport of mucus toward pharynx
Thick sputum → becomes fluid
👉 Clinical benefit:
Easier expectoration
Relief from chest congestion
Improved airway patency
Reduced obstruction
Better ventilation
| Effect | Mechanism | Clinical Benefit |
|---|---|---|
| Mucus thinning | Viscosity reduction | Easy expectoration |
| Improved clearance | Ciliary action | Airway cleaning |
| Reduced obstruction | Liquefaction | Better airflow |
Viscous mucus
→ Drug action
→ Liquefaction
→ Mucociliary transport
→ Expulsion of sputum
Shows:
Thick vs thin mucus
Ciliary transport
Clinical importance
Explains therapeutic role
Basis of use in productive cough
Expectorants → increase secretions
Mucolytics → reduce viscosity
Acetylcysteine → breaks disulfide bonds (MOST IMPORTANT)
Final effect → liquefied sputum + improved clearance
Essential in:
Productive cough
COPD
Bronchiectasis
Prodrug → converted to Ambroxol
Mechanism:
Depolymerizes mucopolysaccharides
↓ viscosity of mucus
👉 Key Point:
Indirect mucolytic via active metabolite
Active metabolite of bromhexine
Stimulates surfactant production
Enhances mucociliary clearance
Reduces mucus viscosity
👉 Clinical advantage:
Improves airway lubrication + clearance
Breaks disulfide bonds (–S–S–)
Rapid liquefaction of mucus
Replenishes glutathione
Neutralizes free radicals
Mechanism:
Restores hepatic glutathione
Detoxifies toxic metabolite (NAPQI)
👉 Cross-link integration (pharmacology core concept)
| Drug | Key Mechanism | Special Feature |
|---|---|---|
| Bromhexine | Prodrug → Ambroxol | Indirect mucolytic |
| Ambroxol | Surfactant ↑ | Enhances clearance |
| Acetylcysteine | Disulfide bond break | Antioxidant + antidote |
Bromhexine
→ Ambroxol
→ ↓ mucus viscosity + ↑ surfactant
Acetylcysteine
→ Breaks bonds
→ Rapid mucus liquefaction
Thick sputum present
Drugs help:
Liquefy mucus
Facilitate expectoration
Chronic mucus hypersecretion
Improves:
Airway clearance
Breathing
Dilated bronchi → mucus accumulation
Drugs help prevent:
Infection
Airway blockage
Post-infective cough with sputum
Cystic fibrosis (advanced setting)
| Condition | Role |
|---|---|
| Productive cough | Liquefy sputum |
| COPD | Improve clearance |
| Bronchiectasis | Prevent mucus retention |
Thick sputum
→ Mucolytics
→ Liquefaction
→ Easy expectoration
Nausea
Vomiting
Epigastric discomfort
👉 Common with:
Acetylcysteine
Especially with inhaled mucolytics
👉 Mechanism:
Airway irritation
👉 Prevention:
Use bronchodilator if needed
Allergic reactions (rare)
Bad taste (acetylcysteine)
| Effect | Cause | Drug |
|---|---|---|
| GI irritation | Direct irritation | Acetylcysteine |
| Bronchospasm | Airway irritation | Inhaled mucolytics |
| Allergy | Hypersensitivity | All drugs |
Shows:
Mucus breakdown
Possible airway irritation
Clinical importance
Balance benefit vs risk
Important in COPD patients
Bromhexine → prodrug of ambroxol
Ambroxol → ↑ surfactant + ↑ clearance
Acetylcysteine →
Mucolytic + antioxidant + antidote (VERY IMPORTANT)
Used in:
Productive cough
COPD
Bronchiectasis
Adverse effects:
GI irritation (common)
Bronchospasm (rare but important)
Chronic inflammatory airway disease
Characterized by:
Reversible airflow obstruction
Airway hyperresponsiveness
Episodic symptoms (wheezing, dyspnea, cough)
Trigger:
Allergen exposure
Mechanism:
IgE antibodies bind to mast cells
→ Mast cell degranulation
Histamine
Leukotrienes
Prostaglandins
Bronchospasm (immediate)
Increased vascular permeability
Mucus secretion
Occurs after 4–8 hours
Recruitment of inflammatory cells:
Eosinophils
T lymphocytes
IL-4
IL-5
IL-13
Persistent inflammation
Airway damage
Increased hyperresponsiveness
Constriction of bronchial smooth muscle
Major cause of acute symptoms
Due to increased vascular permeability
Leads to airway narrowing
Thick mucus plugs
Obstruct airway lumen
Exaggerated response to stimuli
Even minor triggers → severe constriction
| Feature | Early Phase | Late Phase |
|---|---|---|
| Onset | Immediate | 4–8 hours |
| Cells | Mast cells | Eosinophils, T cells |
| Mediators | Histamine, leukotrienes | Cytokines |
| Effect | Bronchospasm | Inflammation |
Allergen exposure
→ IgE activation
→ Mast cell degranulation
→ Mediator release
→ Bronchospasm (early)
→ Inflammatory cell recruitment
→ Chronic inflammation (late)
Central role in early phase
Release:
Histamine
Leukotrienes
Major cells in late phase
Cause:
Tissue damage
Chronic inflammation
Regulate immune response
Release cytokines
Causes:
Bronchoconstriction
Increased permeability
LTC4, LTD4, LTE4
👉 Effects:
Powerful bronchoconstriction
Increased mucus secretion
IL-4 → IgE production
IL-5 → eosinophil activation
IL-13 → mucus secretion
| Cell | Mediator | Effect |
|---|---|---|
| Mast cell | Histamine | Bronchospasm |
| Eosinophil | Cytokines | Inflammation |
| T lymphocyte | IL-4, IL-5, IL-13 | Immune response |
| Leukotrienes | LTC4, LTD4, LTE4 | Strong bronchoconstriction |
Mast cells → immediate reaction
Eosinophils → chronic inflammation
Leukotrienes → most potent bronchoconstrictors
Shows:
Early + late phase
Cellular involvement
Airway changes
Clinical importance
Basis for drug therapy:
Bronchodilators → early phase
Steroids → late phase
Asthma = chronic inflammatory airway disease
Early phase → IgE + mast cell degranulation
Late phase → eosinophil-mediated inflammation
Key mediators:
Histamine
Leukotrienes (MOST IMPORTANT)
Core features:
Bronchospasm
Edema
Mucus
Hyperresponsiveness
Based on:
Symptom frequency
Night awakenings
Activity limitation
Lung function (FEV₁/PEF)
Guides stepwise therapy
Symptoms:
< 2 days/week
Night symptoms:
< 2/month
Lung function:
Normal between attacks
👉 Features:
Mild, episodic
Symptoms:
2 days/week (not daily)
Night symptoms:
3–4/month
👉 Features:
Minor activity limitation
Symptoms:
Daily
Night symptoms:
1/week
👉 Features:
Moderate limitation
Reduced lung function
Symptoms:
Continuous
Night symptoms:
Frequent
👉 Features:
Severe limitation
Markedly reduced lung function
| Feature | Intermittent | Mild | Moderate | Severe |
|---|---|---|---|---|
| Symptoms | <2/week | >2/week | Daily | Continuous |
| Night symptoms | <2/month | 3–4/month | >1/week | Frequent |
| Activity | Normal | Mild limitation | Moderate | Severe |
| Lung function | Normal | ↓ mild | ↓ moderate | ↓ severe |
Severity ↑
→ Inflammation ↑
→ Drug requirement ↑
Two major groups:
Bronchodilators → relieve symptoms
Anti-inflammatory drugs → control disease
Salbutamol
👉 Features:
Rapid onset
Used in:
Acute attack (drug of choice)
Salmeterol
Formoterol
👉 Features:
Long duration (≈12 hours)
Used for:
Maintenance therapy
⚠️ Never used alone (must combine with steroids)
Theophylline
PDE inhibition → ↑ cAMP
Adenosine receptor blockade
Bronchodilation
Narrow therapeutic index (VERY IMPORTANT)
Ipratropium
Tiotropium
Block M3 receptors
↓ bronchoconstriction
More useful in COPD
Add-on in asthma
| Class | Drugs | Mechanism | Use |
|---|---|---|---|
| SABA | Salbutamol | ↑ cAMP | Acute attack |
| LABA | Salmeterol, Formoterol | ↑ cAMP | Maintenance |
| Methylxanthine | Theophylline | PDE inhibition | Add-on |
| Anticholinergic | Ipratropium, Tiotropium | M3 block | COPD/add-on |
β₂ stimulation
→ ↑ cAMP
→ Smooth muscle relaxation
→ Bronchodilation
Shows:
β₂ pathway
Anticholinergic pathway
Theophylline action
Clinical importance
Helps compare drug mechanisms
Basis of combination therapy
Asthma classified into intermittent → severe persistent
Severity determines treatment step
Bronchodilators:
SABA → acute relief (most important)
LABA → maintenance (never alone)
Theophylline → add-on (narrow TI)
Anticholinergics → useful in COPD & add-on in asthma
Target underlying inflammation
Reduce:
Airway edema
Hyperresponsiveness
Frequency of exacerbations
Cornerstone of long-term control
Examples:
Budesonide
Beclomethasone
Examples:
Prednisolone
Used in:
Acute severe asthma
Exacerbations
Bind glucocorticoid receptors
↓ transcription of inflammatory genes
↓ cytokines (IL-4, IL-5, IL-13)
↓ eosinophil activity
↓ mucus production
Potent anti-inflammatory
Prevent airway remodeling
Reduce exacerbations
ICS:
Oral candidiasis
Dysphonia
Systemic:
Adrenal suppression
Osteoporosis
Hyperglycemia
👉 Prevention:
Mouth rinsing after inhalation
| Feature | ICS | Systemic |
|---|---|---|
| Route | Inhalation | Oral/IV |
| Action | Local | Systemic |
| Side effects | Minimal | Significant |
| Use | Maintenance | Acute severe asthma |
Montelukast
Zafirlukast
Block leukotriene receptors
Inhibit effects of:
LTC₄, LTD₄, LTE₄
↓ bronchoconstriction
↓ mucus secretion
↓ inflammation
Mild persistent asthma
Exercise-induced asthma
Aspirin-induced asthma
| Feature | Effect |
|---|---|
| Mechanism | Leukotriene blockade |
| Role | Add-on therapy |
| Special use | Aspirin-induced asthma |
Sodium cromoglycate
Prevent mast cell degranulation
Inhibit mediator release
Prophylactic use only
No role in acute attack
Mild asthma
Exercise-induced asthma
| Feature | Description |
|---|---|
| Action | Prevent mediator release |
| Use | Prophylaxis |
| Limitation | Not for acute relief |
Target specific immune pathways
Used in:
Severe refractory asthma
Omalizumab
Binds IgE
Prevents mast cell activation
Mepolizumab
↓ eosinophil activation
Dupilumab
Blocks cytokine signaling
↓ inflammation
| Drug | Target | Effect |
|---|---|---|
| Omalizumab | IgE | ↓ mast cell activation |
| Mepolizumab | IL-5 | ↓ eosinophils |
| Dupilumab | IL-4/13 | ↓ inflammation |
Allergen
→ IgE activation
→ Mast cell + eosinophil response
→ Biologics block specific step
→ Reduced inflammation
Shows:
IgE pathway
Cytokine pathways
Clinical importance
Used in severe asthma
Personalized therapy
Corticosteroids = most important controller drugs
ICS preferred → fewer side effects
Leukotriene inhibitors → add-on therapy
Mast cell stabilizers → prophylaxis only
Biologics → severe refractory asthma (latest advancement)
Antiasthma drugs act by:
Bronchodilation (symptom relief)
Anti-inflammatory action (disease control)
Examples:
Salbutamol
Salmeterol
Stimulate β₂ receptors
→ Activate adenylyl cyclase
→ ↑ cAMP
→ ↓ intracellular Ca²⁺
→ Smooth muscle relaxation
👉 Result:
Rapid bronchodilation
Examples:
Ipratropium
Tiotropium
Block M3 muscarinic receptors
→ Inhibit parasympathetic bronchoconstriction
→ Bronchodilation
Example:
Theophylline
↓ breakdown of cAMP
→ ↑ cAMP
→ Bronchodilation
Prevents bronchoconstriction
Examples:
Budesonide
Prednisolone
Bind intracellular glucocorticoid receptors
→ Translocate to nucleus
→ ↓ transcription of inflammatory genes
↓ cytokines (IL-4, IL-5, IL-13)
↓ eosinophils
↓ mucus production
Example:
Montelukast
Block leukotriene receptors
OR
Inhibit 5-lipoxygenase pathway
↓ bronchoconstriction
↓ mucus secretion
↓ inflammation
| Drug Class | Mechanism | Final Effect |
|---|---|---|
| β₂ agonists | ↑ cAMP | Bronchodilation |
| Anticholinergics | M3 blockade | Bronchodilation |
| Theophylline | PDE inhibition + adenosine block | Bronchodilation |
| Steroids | ↓ cytokine gene expression | Anti-inflammatory |
| Leukotriene inhibitors | Leukotriene blockade | ↓ inflammation |
β₂ agonists / Theophylline
→ ↑ cAMP
→ Smooth muscle relaxation
Steroids / Leukotrienes
→ ↓ inflammation
→ ↓ airway hyperresponsiveness
→ Improved airflow
Relaxation of airway smooth muscle
Rapid relief of symptoms
👉 Mediated by:
β₂ agonists
Theophylline
Anticholinergics
Reduction in:
Cytokines
Eosinophils
Edema
👉 Mainly by:
Corticosteroids
Leukotriene inhibitors
↓ frequency of attacks
↓ disease progression
👉 Achieved by:
ICS (most important)
Biologics
Improved airway patency
Reduced mucus plugging
Enhanced lung function
| Action | Drug Class | Clinical Benefit |
|---|---|---|
| Bronchodilation | β₂ agonists, anticholinergics | Immediate relief |
| Anti-inflammatory | Steroids, leukotrienes | Long-term control |
| Prevention | ICS, biologics | ↓ exacerbations |
Bronchodilators → symptom relief
Anti-inflammatory drugs → disease control
Shows:
Bronchodilation
Inflammation reduction
Clinical importance
Explains combination therapy
Basis of stepwise treatment
β₂ agonists → ↑ cAMP → bronchodilation (FASTEST ACTION)
Anticholinergics → block parasympathetic tone
Theophylline → dual mechanism (PDE + adenosine)
Steroids → most important anti-inflammatory drugs
Leukotrienes → block key inflammatory mediators
Final effects:
Bronchodilation
Inflammation control
Prevention of exacerbations
Choice of route determines:
Onset of action
Systemic side effects
Drug efficacy in lungs
Direct delivery to lungs
Small doses required
👉 Advantages:
Rapid onset
Minimal systemic exposure
Systemic absorption
Requires higher dose
👉 Disadvantages:
Delayed onset
More side effects
Oral drugs undergo:
Hepatic first-pass metabolism
👉 Result:
Reduced bioavailability
Increased dose requirement
Bypass first-pass metabolism
Act locally in lungs
Theophylline
Well absorbed orally
Extensive hepatic metabolism (CYP enzymes)
Small difference between:
Therapeutic dose
Toxic dose
↑ levels:
Liver disease
Macrolides
↓ levels:
Smoking
👉 Clinical implication:
Requires therapeutic drug monitoring
| Feature | Inhalational | Oral |
|---|---|---|
| Onset | Rapid | Slow |
| Dose | Low | High |
| First-pass effect | Absent | Present |
| Side effects | Minimal | More |
Inhalation
→ Direct lung delivery
→ Rapid effect
→ Less systemic toxicity
Pressurized aerosol device
Delivers fixed dose
Requires coordination
Improper technique reduces efficacy
Breath-activated device
No coordination needed
Requires adequate inspiratory effort
Converts liquid drug → aerosol
Used in:
Acute severe asthma
Children
Easy to use
No coordination needed
| Feature | MDI | DPI | Nebulizer |
|---|---|---|---|
| Coordination | Required | Not required | Not required |
| Drug delivery | Moderate | Good | Excellent |
| Use | Routine | Routine | Emergency |
| Cost | Low | Moderate | High |
Rapid action
Targeted delivery to lungs
Less systemic side effects
Lower dose requirement
Inhaler use
→ Drug reaches lungs
→ Local action
→ Bronchodilation / anti-inflammatory effect
Shows:
MDI vs DPI vs nebulizer
Drug delivery efficiency
Clinical importance
Technique determines efficacy
Poor technique → treatment failure
Inhalational route → best for asthma drugs
Avoids first-pass metabolism
Theophylline → narrow therapeutic index (VERY IMPORTANT)
Delivery systems:
MDI → most common
DPI → easier use
Nebulizer → acute severe cases
Proper technique = key to success
Correct technique = adequate lung deposition
Poor technique → treatment failure despite correct drug
Shake inhaler
Exhale fully
Place mouthpiece properly
Press inhaler + slow deep inhalation
Hold breath for ~10 seconds
Exhale slowly
Pressing inhaler at wrong time
👉 Effect:
Drug deposits in oropharynx instead of lungs
Patient exhales immediately
👉 Effect:
Reduced drug absorption
Especially important in:
Children
Elderly
👉 Effect:
↑ oropharyngeal deposition
↓ lung delivery
Device attached to MDI
Improves:
Drug delivery
Coordination
👉 Benefits:
↓ side effects (e.g., candidiasis)
↑ lung deposition
| Error | Effect | Clinical Outcome |
|---|---|---|
| Poor coordination | Drug loss | Reduced efficacy |
| No breath hold | Less absorption | Poor control |
| No spacer | Oropharyngeal deposition | Side effects ↑ |
Correct technique
→ Drug reaches lungs
→ Effective therapy
Wrong technique
→ Drug wasted
→ Treatment failure
Shows:
Proper vs improper technique
Drug deposition differences
Clinical importance
One of the most common causes of uncontrolled asthma
Tremor
Tachycardia
Palpitations
👉 Mechanism:
β₂ → skeletal muscle tremor
β₁ cross-stimulation → cardiac effects
Oral candidiasis
Dysphonia
👉 Prevention:
Mouth rinsing
Spacer use
Adrenal suppression
Osteoporosis
Hyperglycemia
Arrhythmias
Seizures
CNS stimulation
👉 Reason:
Narrow therapeutic index (VERY IMPORTANT)
Dry mouth
Throat irritation
| Drug Class | Adverse Effects |
|---|---|
| β₂ agonists | Tremor, tachycardia |
| Steroids | Candidiasis, adrenal suppression |
| Theophylline | Arrhythmia, seizures |
| Anticholinergics | Dry mouth |
β₂ agonists → sympathetic effects
Steroids → immunosuppression
Theophylline → toxicity due to narrow TI
Anticholinergics → parasympathetic blockade
Shows:
Multi-drug adverse effects
Mechanism-based comparison
Clinical importance
Helps in drug selection
Prevents complications
Inhaler technique = key determinant of success
Most common errors:
Poor coordination
No breath holding
No spacer
Adverse effects:
β₂ → tremor, tachycardia
Steroids → candidiasis
Theophylline → dangerous toxicity
Anticholinergics → dry mouth
Life-threatening condition
Characterized by:
Severe bronchospasm
Hypoxia
Poor response to usual therapy
👉 Immediate management required
Severe dyspnea
Inability to speak full sentences
Use of accessory muscles
Silent chest (very severe)
↓ SpO₂
High-flow oxygen
Maintain SpO₂ > 94%
Nebulized Salbutamol
Drug of choice
Repeated dosing
👉 Can combine with:
Ipratropium (additive effect)
IV:
Hydrocortisone
Oral:
Prednisolone
👉 Action:
Reduce airway inflammation
Prevent relapse
IV Magnesium sulfate
👉 Mechanism:
Smooth muscle relaxation
Used in:
Severe refractory cases
IV fluids
Monitoring:
SpO₂
ABG
Avoid sedatives
| Drug | Role |
|---|---|
| Salbutamol | Rapid bronchodilation |
| Ipratropium | Add-on bronchodilator |
| Steroids | Anti-inflammatory |
| Magnesium sulfate | Severe cases |
Severe asthma
→ Oxygen
→ Nebulized bronchodilator
→ Steroids
→ Add magnesium (if needed)
→ Monitor
Shows:
Oxygen + nebulization
Stepwise management
Clinical importance
Frequently asked in exams
Critical life-saving protocol
Severe asthma attack not responding to standard therapy
👉 Medical emergency
Severe bronchospasm
Mucus plugging
Air trapping → hyperinflation
Respiratory failure
Extreme breathlessness
Silent chest
Cyanosis
Altered consciousness (late)
SpO₂
ABG
Cardiac monitoring
Continuous nebulized:
Salbutamol
High-dose IV steroids
Maintain adequate oxygenation
Mechanical ventilation (if needed)
Life-threatening condition
Requires ICU care
Delay → respiratory arrest
| Feature | Acute Severe Asthma | Status Asthmaticus |
|---|---|---|
| Response to therapy | Partial | None |
| Severity | High | Extreme |
| Management | Emergency | ICU |
| Risk | High | Very high |
Acute severe asthma
→ Treat aggressively
Failure to respond
→ Status asthmaticus → ICU management
Shows:
Airway narrowing
Mucus plugging
Clinical importance
Explains severity
Guides ICU intervention
Acute severe asthma = medical emergency
First-line:
Oxygen
Nebulized Salbutamol
Steroids
Magnesium sulfate → add in severe cases
Status asthmaticus:
No response to treatment
Requires ICU + possible ventilation
Treatment is stepwise escalation
Based on:
Severity
Symptom control
👉 Aim:
Achieve control with minimum effective therapy
Reliever only
Salbutamol (SABA) PRN
Add low-dose ICS
Budesonide
👉 First-line controller therapy
ICS + LABA
Salmeterol / Formoterol
👉 Improves symptom control
High-dose ICS + LABA
Consider add-on:
Anticholinergics
Leukotriene modifiers
Add biologics
Omalizumab
Mepolizumab
👉 Severe refractory asthma
Once control achieved:
Gradually reduce dose
| Step | Treatment |
|---|---|
| 1 | SABA PRN |
| 2 | Low-dose ICS |
| 3 | ICS + LABA |
| 4 | High-dose ICS + LABA |
| 5 | Add biologics |
Severity ↑
→ Step ↑
→ Drug intensity ↑
| Feature | Asthma | COPD |
|---|---|---|
| Pathology | Inflammatory (reversible) | Obstructive (less reversible) |
| Main drug | ICS | Anticholinergics |
| Response to steroids | Good | Limited |
| Onset | Early | Late |
Asthma
ICS dominant
β₂ agonists important
COPD
Anticholinergics dominant
Tiotropium preferred
Asthma → inflammation-driven → steroids essential
COPD → airflow limitation → bronchodilators essential
Asthma → control inflammation
COPD → relieve obstruction
Trigger:
Physical exertion
👉 Management:
Pre-exercise:
Salbutamol
Leukotriene inhibitors useful
Mechanism:
NSAIDs → ↑ leukotriene production
👉 Features:
Bronchospasm after aspirin intake
👉 Management:
Avoid NSAIDs
Use:
Montelukast
Symptoms worsen at night
👉 Causes:
Circadian variation
Increased vagal tone
👉 Management:
Long-acting drugs:
LABA
Sustained-release theophylline
| Type | Trigger | Treatment |
|---|---|---|
| Exercise-induced | Exercise | SABA before exercise |
| Aspirin-induced | NSAIDs | Leukotriene inhibitors |
| Nocturnal | Night | Long-acting drugs |
With:
Macrolides (e.g., erythromycin)
Fluoroquinolones
👉 Mechanism:
Inhibit hepatic metabolism
Smoking
👉 Mechanism:
Induces liver enzymes
↑ metabolism → ↓ drug levels
Requires:
Dose adjustment
Monitoring
| Factor | Effect |
|---|---|
| Macrolides | ↑ toxicity |
| Fluoroquinolones | ↑ toxicity |
| Smoking | ↓ effect |
Theophylline
→ Narrow therapeutic index
→ Small changes = toxicity risk
Stepwise therapy = core asthma management concept
ICS = most important controller
COPD vs asthma:
Asthma → ICS
COPD → anticholinergics
Special asthma:
Exercise → SABA
Aspirin → leukotrienes
Theophylline:
Highly interaction-prone (VERY IMPORTANT)
Prefer inhalational therapy
Use spacer devices → improves drug delivery
Avoid unnecessary systemic drugs
Salbutamol → acute relief
Budesonide → maintenance
Theophylline
Narrow therapeutic index
Systemic steroids → limit long-term use
Nebulizers preferred in:
Young children
Monitor growth (ICS long-term use)
Maintain adequate maternal oxygenation
Avoid uncontrolled asthma (greater risk than drugs)
Salbutamol
Budesonide
Systemic steroids (only if necessary)
Poorly controlled asthma → fetal hypoxia
Hence:
Treatment is safer than no treatment
| Population | Preferred Therapy | Avoid |
|---|---|---|
| Pediatrics | SABA + ICS (inhaled) | Theophylline (caution) |
| Pregnancy | SABA + ICS | Unnecessary systemic drugs |
Children → use spacer + inhalation
Pregnancy → control asthma = protect fetus
Attach to MDI
👉 Benefits:
↑ lung deposition
↓ oropharyngeal deposition
↓ side effects (candidiasis)
👉 Prevents:
Oral candidiasis
Dysphonia
Use lowest effective dose
Growth (children)
Signs of steroid toxicity
| Method | Benefit |
|---|---|
| Spacer | ↓ local side effects |
| Mouth rinse | Prevent candidiasis |
| Dose control | ↓ systemic toxicity |
Proper technique + precautions
→ Max benefit + minimum side effects
Drug of choice:
Salbutamol
👉 Rapid bronchodilation
First-line:
Budesonide
👉 Controls inflammation
Add:
LABA
Leukotriene modifiers
Use biologics:
Omalizumab
Mepolizumab
Reliever vs controller concept:
SABA → relief
ICS → control
| Condition | Drug |
|---|---|
| Acute attack | SABA |
| Maintenance | ICS |
| Severe asthma | Biologics |
Acute → bronchodilation
Chronic → anti-inflammatory
Severe → targeted therapy (biologics)
Shows:
Acute vs chronic management
Stepwise escalation
Clinical importance
Helps in real-life prescribing
Frequently asked in exams
Pediatrics → use inhalers + spacer
Pregnancy → safe drugs = SABA + ICS
Prevent adverse effects:
Spacer
Mouth rinse
Rational drug use:
SABA → acute
ICS → maintenance
Biologics → severe asthma
| Class | Subtype | Drugs |
|---|---|---|
| Central acting | Opioid | Codeine, Pholcodine |
| Non-opioid | Dextromethorphan, Noscapine | |
| Peripheral acting | — | Levodropropizine, Benzonatate |
| Feature | Opioid | Non-opioid |
|---|---|---|
| Example | Codeine | Dextromethorphan |
| Mechanism | μ-receptor | NMDA block |
| Sedation | High | Low |
| Respiratory depression | Present | Minimal |
| Abuse potential | High | Low |
| Feature | Expectorants | Mucolytics |
|---|---|---|
| Mechanism | ↑ secretion | ↓ viscosity |
| Action | Dilution | Breakdown |
| Drugs | Guaifenesin | Bromhexine, Ambroxol, Acetylcysteine |
| Role | Mild cough | Thick sputum |
| Class | Mechanism | Drugs |
|---|---|---|
| Central | Suppress cough center | Codeine, Dextromethorphan |
| Peripheral | Block receptors | Levodropropizine |
| Expectorants | ↑ secretion | Guaifenesin |
| Mucolytics | ↓ viscosity | Acetylcysteine |
| Class | Subclass | Drugs | Action |
|---|---|---|---|
| Bronchodilators | SABA | Salbutamol | Rapid relief |
| LABA | Salmeterol, Formoterol | Long acting | |
| Methylxanthine | Theophylline | ↑ cAMP | |
| Anticholinergic | Ipratropium, Tiotropium | M3 block | |
| Anti-inflammatory | ICS | Budesonide | ↓ inflammation |
| Systemic | Prednisolone | Severe cases | |
| Leukotriene | Montelukast | Block LT | |
| Mast stabilizer | Cromoglycate | Prevent release | |
| Biologics | Anti-IgE | Omalizumab | ↓ IgE |
| Anti-IL5 | Mepolizumab | ↓ eosinophils | |
| Anti-IL4/13 | Dupilumab | ↓ cytokines |
| Feature | SABA | LABA |
|---|---|---|
| Example | Salbutamol | Salmeterol |
| Onset | Rapid | Slow |
| Duration | Short | Long (~12h) |
| Use | Acute attack | Maintenance |
| Monotherapy | Yes | No (with ICS) |
| Feature | ICS | Systemic |
|---|---|---|
| Route | Inhaled | Oral/IV |
| Action | Local | Systemic |
| Side effects | Low | High |
| Use | Maintenance | Severe asthma |
| Feature | Ipratropium | Tiotropium |
|---|---|---|
| Duration | Short | Long |
| Use | Acute/add-on | Maintenance |
| Preference | Asthma | COPD |
| Drug | Mechanism | Use |
|---|---|---|
| Montelukast | LT receptor blocker | Mild asthma |
| Zafirlukast | LT receptor blocker | Add-on therapy |
| Factor | Effect |
|---|---|
| Macrolides | ↑ toxicity |
| Fluoroquinolones | ↑ toxicity |
| Smoking | ↓ effect |
| Feature | Asthma | COPD |
|---|---|---|
| Main drug | ICS | Anticholinergics |
| Reversibility | High | Low |
| Role of steroids | Major | Limited |
| Preferred drug | Budesonide | Tiotropium |
| Drug | Target | Indication |
|---|---|---|
| Omalizumab | IgE | Allergic asthma |
| Mepolizumab | IL-5 | Eosinophilic asthma |
| Dupilumab | IL-4/13 | Severe asthma |
| Feature | MDI | DPI | Nebulizer |
|---|---|---|---|
| Coordination | Required | Not required | Not required |
| Drug delivery | Moderate | Good | Excellent |
| Use | Routine | Routine | Emergency |
| Cost | Low | Moderate | High |
Antitussives → dry cough only
Mucolytics → productive cough
ICS → most important asthma drug
SABA → acute attack
LABA → never alone
Theophylline → interaction-prone
Biologics → severe asthma
Inhalation → best route
Flow:
Receptors (larynx, trachea, bronchi)
→ Vagus nerve (afferent)
→ Medullary cough center
→ Motor nerves (efferent)
→ Respiratory muscles
→ Cough
Flow:
Central drugs
→ Suppress medullary center
→ ↑ cough threshold
Peripheral drugs
→ Inhibit airway receptors
→ ↓ afferent signals
→ Reduced cough
Flow:
Thick mucus
→ Mucolytics → ↓ viscosity
→ Expectorants → ↑ secretion
→ Ciliary movement
→ Mucus clearance
Flow:
Allergen exposure
→ IgE activation
→ Mast cell degranulation
→ Histamine + leukotrienes
→ Bronchospasm (early phase)
→ Eosinophil recruitment
→ Cytokine release
→ Chronic inflammation (late phase)
Flow:
Membrane phospholipids
→ Arachidonic acid
→ 5-Lipoxygenase
→ LTC₄, LTD₄, LTE₄
→ Bronchoconstriction + mucus
→ Blocked by leukotriene inhibitors
Flow:
β₂ agonists
→ ↑ cAMP
→ Smooth muscle relaxation
Anticholinergics
→ M3 blockade
→ ↓ bronchoconstriction
Theophylline
→ PDE inhibition + adenosine block
→ ↑ cAMP
→ Bronchodilation
Flow:
Steroid enters cell
→ Binds receptor
→ Nucleus entry
→ ↓ cytokine gene transcription
→ ↓ inflammation
Flow:
Step 1 → SABA
→ Step 2 → Low-dose ICS
→ Step 3 → ICS + LABA
→ Step 4 → High-dose ICS + LABA
→ Step 5 → Biologics
Flow:
Inhalation
→ Airway deposition
→ Local drug action
→ Bronchodilation / anti-inflammatory effect
Flow:
Acute severe asthma
→ Oxygen
→ Nebulized SABA
→ Add ipratropium
→ IV steroids
→ Magnesium sulfate (if severe)
→ Monitor / ICU
Cough → vagus-mediated reflex
Mucus → clearance depends on viscosity + cilia
Asthma → early (bronchospasm) + late (inflammation)
Leukotrienes → key bronchoconstrictors
Steroids → genomic anti-inflammatory action
Stepwise therapy → core exam concept
Emergency asthma → oxygen + SABA + steroids
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