Describe the pathophysiology of asthma
Can be divided into immediate and late phase.
Immediate phase - allergen causes interaction of mast cells with IgE. Results in release of histamine and bronchospasm.
Late phase - Leukocytes enter area. Results in exacerbation of bronchospasming, thickening of basement membrane, oedema, and mucus production. Epithelial damage leads to increased exposure of the sensory irritant receptors, vicious cycle.
What receptors do asthma drugs act on in the airways? What are the effects?
beta 2 receptors - bronchodilation, reduced histamine release, increased mucociliary clearance
Explain the 5 step asthma control
- Step 1: Inhaled short-acting β2-agonist when required
- Step 2: Addition of inhaled steroids (200-800mg a day)
- Step 3: Addition of inhaled long acting β2-agonist (LABA)
- Step 4: Increase inhaled steroid levels or addition of fourth drug (i.e. leukotriene receptor antagonist, theophylline, or oral β2-agonist tablet)
- Step 5: Addition of oral steroid tablet or Anti-IgE therapy
Once asthma controlled, stepping down is recommended.
Explain how bronchodilators work.
- Bind to beta 2 receptors
- Results in increased cAMP and reduction of intracellular calcium, which reduces muscle contractions.
- Also increases calcium activated potassium currents, hyperpolarising muscle cells further
Name the bronchodilators
What are the ADRs of bronchodilators?
Systemic adrenergic effects - tachycardia, palpitations, tremors
Which is why they are preferentially given inhaled not orally
What is the main DDI of bronchodilators?
beta antagonists e.g propanolol
How do corticosteroids exert their anti-inflammatory effects?
Transactivation - Suppress gene transcription in inflammatory cells
Transrepression - Represses the inflammatory responses seen
Induces apoptosis in inflammatory cells and reduces number of mast cells in respiratory mucosa. Corticosteroids work better with eosinophilic asthma
What are the 2 types of asthma?
eosinophilic and non eosinophilic
Why might a combined inhaler be preferable to non combined? What is a combined inhaler?
Combined inhaler - contains LABA and glucocorticoids e.g. symbicort.
Ease of use, good compliance, cheaper, safer
How do leukotriene receptor antagonists work?
LTC released from mast cells and eosinophils to induce bronchoconstriction, mucus secretion, oedema and inflammation. LRA therefore inhibits.
How do anticholinergics work?
Muscarinic receptor antagonists. Bind to and block M3 receptors preventing bronchoconstriction and mucus secretion
When would anticholinergic be used?
Used to augment beta 2 agonists or where beta 2 agonist action is contraindicated e.g. IHD
Give 2 examples of methylanthines
theophylline and aminophylline
How do methylanthines work?
antagonising adenosine receptors.
Why is methylanthines not used more often?
ADRs too high and narrow therapeutic window
What are the ADRs of methylanthines?
psychomotor agitation and tachycardia.