BRONCHIAL ASTHMA
- Asthma is chronic inflammation disease of air way that is characterized by increase responsiveness of tracheobronchial tree to a multiplicity of stimuli.
- Results:
- Narrowing of air tubes
- Increased secretion
- Mucosal oedema
- Mucous plugging
- Dyspnoea (shortness of breath)
- Wheezing
- Cough (persistent)
STIMULUS
· Tobacco smoke
· Infections such as colds, flu, or pneumonia
· Allergens such as food, pollen, mold, dust mites, and pet dander
· Exercise
· Air pollution and toxins
· Weather, especially extreme changes in temperature
· Drugs (such as aspirin, NSAID, and beta-blockers)
· Food additives
· Emotional stress and anxiety
· Singing, laughing, or crying
· Smoking, perfumes, or sprays
· Acid reflux
· Occupational factors
ETIOLOGICAL CLASSIFICATION
PATHOPHYSIOLOGY OF ASTHMA
1. Chronic inflammation
2. Airway hyperresponsiveness
CHRONIC INFLAMMATION
· It involves respiratory mucosa from trachea to terminal bronchioles, predominantly in the bronchi.
· Activation of mass cell infiltration of eosinophils and T-helper-2 (Th-2) lymphocytes.
· Th-2 response interleukin 4, 5, and 13.
· IL-13, 4 and 9 activates mass cell.
· IL-13 stimulate mucus production.
· IL-5 stimulate eosinophil production.
INFLAMMATORY CELL | MEDIATORS | EFFECTS |
· Mass cells · Eosinophils · Th-2 cells · Basophils · Neutrophils · Platelets | · Histamine · Leukotrienes · Prostanoids · PAF · Adenosine · Endothelin · NO · Cytokines · Chemokines · Growth factor | · Bronchospasm · Plasma exudation · Mucus secretion · Structural changes |
STRUCTURAL CELLS | ||
· Epithelial cells · Smooth muscle cells · Endothelial cells · Fibroblast · Nerves |
AIR-WAY HYPERRESPONSIVENESS
· The excessive bronchoconstriction response to multiple inhaled triggers that would have no effects on normal air-ways.
ASTHMA TRIGGERS
· Allergens
· Virus infection
· Drugs
· Exercise
· Food
· Air pollutants
· Physical factors
· GERD
· Stress
· Occupational factor
COPD
· Chronic obstructive pulmonary disease is a chronic inflammatory lungs disease results obstruction of air way, dyspnea, decrease blood oxygen levels and increase carbon dioxide levels.
· Risk factor
o Smoking and old age
· Treatment
o Bronchodilators
o Oxygen therapy
o Antibiotics
ANTI-ASTHMATIC DRUGS
- Bronchodilators:
· ß2 sympathomimetics (agonists):
o Salbutamol,
o Salmeterol,
o Bambuterol,
o Fometerol,
o Rimeterol,
o Bitolterol and Terbutaline (nonspecific –ephedrine, adrenaline and orciprenaline)
· Methylxanthines:
o theophylline and aminophylline derivatives.
· Anticholinergics:
o ipratropium bromide and tiotropium bromide
2. Mast cell stabilizers:
· sodium chromoglycate and ketotifen
3. Leukotriene antagonists:
· Montelukast and zafirlukast
4. Corticosteroids:
· Systemic: hydrocortisone and prednisolone
· Inhalation: beclomethasone dipropionate, budesonide, fluticasone propionate, flunisolide
5. Anti-IgE antibody:
· omalizumab
INVESTIGATIONS
· pulmonary function test (Spirometry)
o estimate degree of obstruction
o decrease force expiratory volume in 1 second (FEV), FEV1, forced vital capacity (FVC), peak expiratory flow (PEF).
· Arterial blood-gas analysis
· Skin hypersensitivity test
· Sputum and blood eosinophilia
· Elevated serum IgE levels.
MECHANISM OF ACTION
Drugs action | ||||
Class | Mechanism of action | Uses | Pharmacokinetics | Interaction |
Short acting β2-Agonist · Albuterol | β2-selective agonist. ↑cAMP – Bronchodilation | DOC: Acute Asthma | Inhalation (Aerosol), Duration: 2-4hrs | Tremor, Tachycardia |
Long acting β2-Agonist · Salmeterol · Formeterol · Indacaterol · Vilanterol | β2-selective agonist. ↑cAMP – Bronchodilation | Salbutamol and formeterol – Asthma (Prophylaxis), Indacaterol and Vilanterol – COPD | Inhalation (Aerosol), Duration: 12-24hrs | Tremor, Tachycardia, cardiovascular events |
Non-selective sympathomimetics · Epinephrine · Isoproterenol | Nonselective β activation | Asthma | Oral Duration 1-2hrs | Sympathomimetic effects |
Indirect acting sympathomimetics · Ephedrine | Releases stored catecholamines. Causes nonselective sympathetic effects | Asthma | Oral Duration 6-8hrs | Insomnia, tremor, seizures, arrhythmia |
Methylxanthines · Theophylline | Phosphodiesterase inhibition, adenosine receptor antagonist | Asthma (Prophylaxis) against nocturnal attacks | Oral-slow release Duration: 12hrs | Insomnia, tremor, seizures, arrhythmia |
Anti-muscarinic agents · Ipratropium · Tiotropium · Aclidinium | Muscarinic antagonists. Decrease conc. Ca2+ produce bronchodilation | Asthma, COPD | Inhalation (Aerosol), Duration: several hours | Dry mouth, cough |
Mast cell stabilizers · Cromoglycate | educe release of inflammatory and bronchoconstrictor mediators from sensitized mast cells | Rarely used prophylaxis of asthma; cromolyn also used for ophthalmic, nasopharyngeal, and gastrointestinal allergy | Inhaled aerosol Duration: 3–6hrs | Cough |
Leukotrienes antagonists · Montelukast · Zafirlukast · Zileuton | Inhibitor of lipoxygenase. Reduces synthesis of leukotrienes |
Asthma (Prophylaxis) | Oral-12-24hrs | Minimal effects or elevated liver enzyme |
Corticosteroids Inhalation · Beclomethasone | Inhibition of phospholipase A2. Reduces expression of cyclooxygenase | DOC prophylaxis Asthma | Inhalation Duration: 10-12hrs | Pharyngeal candidiasis |
Corticosteroids Systemic · Prednisone | Severe refractory chronic asthma | Oral – 12-24hrs |
| |
Antibodies · Omalizumab | Binds IgE antibodies on mast cells; reduces reaction to inhaled antigen | Severe refractory chronic asthma | Parenteral | Extremely expensive, long term toxicity not yet well reported |
Hi….!! My name is Smrutiranjan Dash, From Odisha, India. Professionally I am Assistant Professor at The Pharmaceutical College, Barpali, Odisha, department of Pharmacology.