Airway Control Flashcards
Give some background on asthma pathophysiology.
Mucosal oedema + bronchoconstriction + mucus plugging
All lead by Th2-driven inflammation
Which leads to bronchial hyperresponsiveness
And might be the reason for airway remodelling.
What happens in terms of airway remodelling in asthma?
Mucous gland hyperplasia Subepithelial fibrosis Epithelium desquamation Airway wall thickening Increased smooth muscle mass
Where do the airway control drugs target?
Smooth muscle dysfunction (^contraction+^Cytokine)
Beta-2 agonist
- Short-acting BA: Salbutamol
- Long-acting BA: Formoterol
Inflammation(immune cells(T cells/mast cells/eosinophils)
Steroids (CS)
Inhaled CS: Budesonide
Oral CS: Prednisolone `
How is asthma a heterogeneous disease?
Pathologically
- Eosinophilic versus neutrophillic inflammation
Symptom patterns and triggers of exacerbations
Response to treatment
What are the 5 steps to asthma management?
Step 1: Mild intermittent asthma Step 2: Regular preventer therapy Step 3: Add-on therapy Step 4: Persistent poor control Step 5: Continuous or frequent use of oral steroids
Describe step one in terms of asthma therapy.
Mild intermittent asthma
Short-acting beta2-agonists
(Salbutamol, terbutaline)
Used for symptom relief through reversal of bronchoconstriction
Prevention of bronchoconstriction i.e. on exercise
Short-acting B2-agonists should only be used on an as-required basis
If used regularly, they reduce asthma control
What is the mechanism of action of Beta2-agonists?
They act on B2 adrenoceptors in airway smooth muscle
This leads to an increase in cAMP and leads to more PKA which leads to
Relaxation
and
Inhibition of agonist-induced contraction
There are other links and this pathway isn’t well known
What are some different classes of B2-agonists?
Fast onset, short duration: - Inhaled terbutaline - Inhaled salbutamol Fast onset, long duration: - Inhaled formoterol Slow onset, long duration - Inhaled salmeterol - (Oral bambuterol) (not used) Slow onset, slow duration (Not used anymore) - Oral terbutaline - Oral salbutamol - Oral formoterol
What are some side effects of B2-agonist?
Adrenergic
Tachycardia
Palpitations
Tremor
Describe step 2 in terms of asthma therapy.
Regular preventer therapy
Inhaled corticosteroids
Start when:
- Using B2-agonists >3 times/week
- Symptoms >3 times/week
- Waking at least once a week
- Exacerbation requiring oral steroids in last two years
Why are inhaled corticosteroids used in asthma treatment?
They work to reduce inflammation
Improve symptoms
Improve lung function
Reduce exacerbations
Prevent death
How do inhaled steroids get into systemic circulation?
Through absorption from lungs and being swallowed and then gut absorption, and what is left after first pass metabolism
Beclomethasone absorbed through gut and lungs
Budesonide and fluticasone undergo extensive first-pass metabolism
What is the relevance of eosinophilic asthma and non-eosinophilic asthma?
Patients with eosinophilic asthma have a better treatment response to inhaled steroids than non-eosinophilic patients
Describe step 3 in terms of asthma therapy.
Add on therapy
BUT before initiating a new drug therapy
- Re-check patient’s medication compliance
- Check inhaler technique
- Eliminate trigger factors
First choice - long-acting B2-agonists (formoterol, salmeterol)
Add-in LAB2A when patients not controlled on 400mcg/day ICS
What are the advantages to long-acting B2-agonists?
Reduce asthma exacerbations
Improve asthma symptoms
Improve lung function
(Not anti-inflammatory on their own, and must always be prescribed in conjunction with an inhaled steroid)
