PHARMACOLOGY OF AIRWAYS
What is Asthma?
Inflamed airway with extra mucus, characterised by wheeze, cough and chest tightness.
50% higher prevalence in black vs white children which is genetic as IgE levels are
genetically influenced.
Environmentally: greater prevalence in city than rural dwellers.
Triggered by:
Respiratory infections
Exercise/ breathing in cold air
Allergens (pets, dust mites, pollution)
ASTHMA PATHOLOGY
1) Allergens stimulate T cells to generate B cell activating cytokines which leads to IgE
production. Therefore, activating mast cells and macrophages.
2) ACUTE PHASE – Release of mediators from macrophage/ mast cells (including
histamines, leukotrienes and cytokines) promoting bronchoconstriction and an
acute asthma attack.
3) These mediators attract more T cells which furthers inflammation and
bronchoconstriction.
4) LATE PHASE – Progressive inflammation, activation of eosinophils releasing toxic
proteins. Damage and loss of epithelium.
5) Therefore, early phase = bronchospasm and late phase = inflammation.
BRONCHODILATORS
BETA-2 AGONISTS
Bronchodilation (most effective bronchodilator)
Inhibit release of histamine and other inflam mediators
Adverse effects: tachycardia, palpitations and pulmonary vasodilatation.
Mechanism of action – Increase intracellular cAMP by adenylate cyclase which
activates Na+/K+ ATPase and reduces Ca2+ dependent coupling of actin and myosin.
Route of administration: inhalation.
XANTHINE DRUGS
Theophylline – oral
Aminophylline – slow IV injection
Mechanism of Action: Interact with G proteins, inhibit cAMP phosphodiesterases preventing
cAMP from converting into AMP; therefore, increasing cAMP levels and causing smooth
muscle relaxation.
Side effects: CNS – Insomnia, nervousness and seizures. CVS – Tachycardia and dysrhythmia
(more likely with aminophylline).
What is Asthma?
Inflamed airway with extra mucus, characterised by wheeze, cough and chest tightness.
50% higher prevalence in black vs white children which is genetic as IgE levels are
genetically influenced.
Environmentally: greater prevalence in city than rural dwellers.
Triggered by:
Respiratory infections
Exercise/ breathing in cold air
Allergens (pets, dust mites, pollution)
ASTHMA PATHOLOGY
1) Allergens stimulate T cells to generate B cell activating cytokines which leads to IgE
production. Therefore, activating mast cells and macrophages.
2) ACUTE PHASE – Release of mediators from macrophage/ mast cells (including
histamines, leukotrienes and cytokines) promoting bronchoconstriction and an
acute asthma attack.
3) These mediators attract more T cells which furthers inflammation and
bronchoconstriction.
4) LATE PHASE – Progressive inflammation, activation of eosinophils releasing toxic
proteins. Damage and loss of epithelium.
5) Therefore, early phase = bronchospasm and late phase = inflammation.
BRONCHODILATORS
BETA-2 AGONISTS
Bronchodilation (most effective bronchodilator)
Inhibit release of histamine and other inflam mediators
Adverse effects: tachycardia, palpitations and pulmonary vasodilatation.
Mechanism of action – Increase intracellular cAMP by adenylate cyclase which
activates Na+/K+ ATPase and reduces Ca2+ dependent coupling of actin and myosin.
Route of administration: inhalation.
XANTHINE DRUGS
Theophylline – oral
Aminophylline – slow IV injection
Mechanism of Action: Interact with G proteins, inhibit cAMP phosphodiesterases preventing
cAMP from converting into AMP; therefore, increasing cAMP levels and causing smooth
muscle relaxation.
Side effects: CNS – Insomnia, nervousness and seizures. CVS – Tachycardia and dysrhythmia
(more likely with aminophylline).
