12) Pharmacology of Asthma Flashcards
What are the features of asthma?
Mucosal oedema
Bronchoconstriction
Mucus plugging
Eventually, airway remodelling and bronchial hyperresponsiveness
What is the early/immediate phase of asthma?
Allergen binds to IgE on mast cells causing release of histamine = bronchospasm
What is the late phase of asthma?
Leucocytes migrate to area in an immune system response
How can asthma vary from person to person?
Eosinophilic v neutrophilic inflammation
Symptoms
Triggers
Treatment response
Describe the autonomic modulation of the airway:
Sympathetic: bronchodilation via beta 2
Parasympathetic: bronchoconstriction via M3
Describe the stepwise approach to treating asthma:
Step up and down with treatment based on symptoms and response to treatment
What are the goals in controlling asthma?
Minimal symptoms
Minimal need for reliever
No exacerbations
No limitation on physical activity
Describe step 1 of the treatment for asthma, including what drugs are used:
Mild intermittent asthma
Uses short acting B2 agonists (salbutamol) for symptom relief as required
What is the mechanism of action of beta 2 agonist?
Bind to B2 receptor (Gs) -> increased cAMP -> inhibition of MLCK -> relaxation of SM
Describe the PK and PD of beta 2 agonists:
Majoirty of drug deposited in upper airway and/or swallowed to be removed by liver
Variation in half life for different onsets and durations
What are some side effects of beta 2 agonists?
Tremor, palpitations, tachycardia
What is drug is given in step 2 and when is it started?
Inhaled corticosteroids
If using Beta agonist: 3 or more times a week, or waking once or more a week
What is the mechanism of action of corticosteroids?
Suppress pro-inflammatory transcription
How are corticosteroids modified for treatment of asthma?
Given lipophilic side chain - increase uptake and rapid inactivation following systemic absoprtion
Which patients have a better treatment response to inhaled steroids?
Eosinophilic asthma
What drugs is given in step 3 of the treatment approach?
Long acting beta 2 agonist (salmeterol or formoterol)
What alternative drugs can be given in step 3/4?
High dose ICS
Leukotriene receptor antagonists
Theophylline
Tiotropium
What is the effect of leukotriene receptor antagonists?
Block the effects of LTC4 - prevent bronchoconstriction, mucus secretion and mucosal oedema
What are the side effects of leukotriene receptor antagonists?
Rare but: angioedema, dry mouth, fever
What effect do methylxanthines (e.g. theophylline) have on the body?
Antagonise adenosine receptors and inhibit phosphodiesterase
What are the side effects of methylxanthines?
Nausea, headache, reflux, psychomotor agitation, tachycardia
What are potential drug interactions with methylxanthines?
Erythromycin, ciprofloxacin
Name some long acting anticholinergics:
Ipratropium, tiotropium
What is the mechanism of action of long acting anticholinergics?
Inhibit bronchoconstriction and mucus secretion at M3 receptor
What are some side effects of long acting anticholinergics?
Dry mouth, urinary retention, glaucoma
What drugs can be used in step 5?
Oral steroids, biological therapies
What is the effect of anti-IgEs (omalizumab)?
Reduces exacerbation rates, prevents IgE binding to receptors so no cross linking of mast cells
What is the effect of anti-IL5 (mepolizumab)?
Reduces peripheral blood and airway eosinophil numbers, reducing exacerbation
If a drug has 10 micron particles where will it be deposited?
Mouth and oropharynx
If a drug has 1-5 micron particles where will it be deposited?
Small airways
If a drug has 0.5 micron particles where will it be deposited?
Alveoli
How is severe acute asthma defined?
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RR >= 25
Pulse >110
Peak flow 33-50% predicted
How is life threatening acute asthma defined?
As in severe plus:
O2<92%, pO2<8kPa, pCO2>4.5kPa
Silent chest, cyanosis, hypotension, bradycardia
What is the treatment for an asthma attack?
High flow O2
Nebulised salbutamol
Oral prednisolone (40mg)
If no improvement: nebulised ipratropium, IV aminophylline
