BRONCHIAL ASTHMA

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

  1. 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 β-Agonist

·         Albuterol

β2-selective agonist. ↑cAMP – Bronchodilation

DOC: Acute Asthma

Inhalation (Aerosol), Duration: 2-4hrs

Tremor, Tachycardia

Long acting β-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

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