Pharmacology of Airway Control Flashcards
Describe the pathophysiology of asthma
Th2-driven and eosinophilic inflammation leads to;
- Mucosal oedema
- Bronchoconstriction
- Mucus plugging
- Airway remodelling
- Smooth muscle dysfunction
- Bronchial hyperresponsiveness (airway remodelling also contributes to this)
What airway remodelling occurs in asthma?
- Mucous gland hyperplasia
- Subepithelial fibrosis
- Epithelium desquamation
- Airway wall thickening
- Increased smooth muscle mass
In what ways is smooth muscle dysfunction in asthma?
- Increased contraction and mass
- Increased cytokines and chemokines
What part of the asthma pathophysiology do ß2 antagonists act on?
The smooth muscle dysfunction
What part of the asthma pathophysiology do steroids act on?
Inflammation
In what respects is asthma a heterogenous disease?
- Pathologically
- Symptom pattern and triggers of exacerbations
- Response to treatment
What is meant by ‘good’ asthma control?
- Minimal symptoms during day and night
- Minimal need for reliever medication
- No exacerbations
- No limitation of physical activity
- Normal lung function
What constitutes normal lung function in asthma?
FEV1 and/or PEF >80% predicted
What should be aimed for regarding asthma control?
Early control, with stepping up or down as required
What should be considered before initiating a new drug therapy for asthma?
- Check compliance with existing therapies
- Check inhaler technique
- Eliminate trigger factors
What are the steps in asthma management?
- Short acting ß2 agonists as required
- Regular preventer
- a. Initial add on therapies - b. Additional add on therapies
- High dose therapies
- Continuous or frequent use of oral steroids
When should moving up a step on asthma management be considered?
If using three doses a week or more
Give two examples of short acting ß-agonists
- Salbutamol
- Terbutaline
How do short-acting ß2 agonists reduce the symptoms of asthma?
Through reversal of bronchoconstriction
When might short acting ß2-agonists be used preventatively?
On exercise
On what basis should short acting ß2-agonists be used?
Only on an as-required basis
What happens if short-acting ß2-agonists are used regularly?
They reduce asthma control
What is the mechanism of action of short acting ß2 agonists?
- Predominant action is on airway smooth muscle, preventing contracting
- Potentially inhibit mast cell degranulation if only used intermittently
How does regular use of ß2 agonists reduce asthma control?
Causes mast cell degranulation in response to allergens to increase
What are the classes of inhaled ß2 agonists?
- Fast onset, short action
- Fast onset, long action
- Slow onset, long action
Give two examples of fast onset, short action ß2 agonists
- Terbutaline
- Salbutamol
What are fast onset, short duration ß2 agonists used for?
Reliever medication
Give three examples of fast onset, long duration ß2 agonists
- Formoterol (12 hours)
- Olodaterol (24 hours)
- Indacaterol (24 hours)
Give two examples of slow onset, long duration ß2 agonists
- Salmetarol (12 hours)
- Vilanterol (24 hours)
What are the side effects of ß2 agonists?
Adrenergic activity, including tachycardia, palpitations, tremor
What kind of drugs are used in regular preventer therapy in step 2 of asthma management?
Inhaled corticosteroids
When should a regular preventer therapy be started in asthma?
- Using ß2 agonists 3 or more times a week
- Symptoms 3 or more times a week
- Waking 1 or more time a week
- Exacerbations requiring steroids in the last 2 years
What point in the asthma pathogenesis does corticosteroids act?
The initial inflammation
What are the advantages of the use of inhaled corticosteroids in asthma treatment?
- Improve symptoms
- Improve lung function
- Reduce exacerbations
- Prevent death
What is the result of the lipophilic substiuents on the D-ring of inhaled corticosteroids?
- A very high affinity for the GCS receptor
- Increased uptake and dwell time in tissue on local application
- Rapid inactivation by hepatic biotransformation following systemic absorption
How do inhaled drugs reach the systemic circulation?
- The swallowed fraction travels to GI tract and gets absorbed in the gut. It then travels to the liver, where some is inactivated in the ‘first pass’, and some active drug remains which then enters the systemic circulation
- Some is deposited in the lungs, and absorbed from the lungs into the systemic circulation
Give an example of an inhaled corticosteroid which is absorbed through the gut and lungs
Beclomethasone
Give two examples of inhaled corticosteroids that undergo extensive first pass metabolism
- Budesonide
- Fluticasone
Why is it important to consider lung absorption with inhaled corticosteroids?
Because lung absorption is still relavent, and high doses of all inhaled corticosteroids have the potenital to produce systemic side effects
Which patients have a better response to inhaled corticosteroids?
Patients with eosinophilic asthma have a better response than non-eosionophilic patients
What should be done before initiating a new drug therapy in asthma?
- Re-check patients medication compliance
- Check inhaler technique
- Eliminate trigger factors
What is the first choice of add on therapy in stage 3 of asthma management?
Long acting ß2 agonists, e.g. formoterol, salmeterol