Airway Control Flashcards
What do the T-helper cells 2 cause?
Secrete interleukins causing
- mucosal oedema
- bronchoconstriction
- mucus plugging
- airway remodelling
- bronchial hyperresponsiveness
What changes in airway remodelling?
Mucous gland hyperplasia Subepithelial fibrosis Epithelial desquamation Airway wall thickening Increased smooth muscle mass
How can asthma vary between individuals?
Pathologically - eg eosinophils vs neutrophil if inflammation
By symptom patterns
Triggers of exacerbation
How it responds to treatment
Which β2 agonists have a fast onset but are short acting?
Inhaled terbutaline
Inhaled salbutamol
Which β2 agonists have fast onset and long acting?
Inhaled formoterol
Which β2 agonists have a slow onset and short acting
Oral salbutamol
Oral terbutaline
Oral formoterol
Which β2 agonists are slow onset and long duration?
Inhaled salmeterol
Oral bambuterol
What are short-acting β2 agonists used for?
Symptom relief though reversal of bronchoconstriction
Prevention of bronchoconstriction eg on exercise
Why should short-acting β2 agonists only be used when required?
If used regularly, can reduce control of asthma
Mechanism of action of short-acting β2 agonists?
β adrenoceptors are coupled to Gs proteins
Activate adenylyl cyclase to convert ATP to cAMP
Increased cAMP activates PKA which phosphorylates L-type calcium channels, increasing calcium entry into cells
Leads to smooth muscle relaxation and inhibition of of agonist-induced contraction
What drives inflammation in asthma?
T-helper cell 2 which secrete interleukins
How do beta-2 agonists reduce bronchoconstriction?
Beta-adrenoceptors coupled to Gs proteins
Activate adenylyl cyclase to convert ATP to cAMP
Increased cAMP activates PKA which
-reduces intracellular Ca2+ concentration
-inhibits MCLK leading to dephosphorylation of myosin
= smooth muscle relaxation
How can beta-2 agonists potentially make asthma worse?
Regular use can increase mash cell degranulation in response to allergens
Side effects of short acting beta-2 agonists?
Tachycardia
Palpitations
Tremor
When are long-acting beta-2 agonists used?
In step 3 as an add-on therapy
- must check patient compliance
- check inhaler technique
- eliminate triggering factors
What is the first choice for a long-acting beta-2 agonist?
Formoterol or salmeterol
What is the onset time and duration of action for beta-2 agonists?
Formoterol works in 1-3 minutes
Salmeterol works in 10-20 minutes
Work for 12 hours
Benefits of long-acting β2 agonists?
Reduce asthma exacerbations
Improve symptoms
Improve lung function
What must long-acting β2 agonists be prescribed with?
An inhaled steroid as they do not have anti-inflammatory properties of their own
What are the different combination inhalers with a long-acting β2 agonist and steroid?
Budesonide/formoterol Beclomethasone/formoterol Fluticasone/formoterol Fluticasone/salmeterol Fluticasone furoate/vilanterol
Why are combined inhalers useful?
Better compliance and easy to use
Only one prescription
Cheaper than two inhalers
When are inhaled corticosteroids introduced?
Using β2 agonist 3 or more times a week
Have symptoms 3 or more times a week
Waking once or more a week
Exacerbation requiring oral steroids in last two years
Mechanism of action of inhaled corticosteroids?
Suppress gene transcription in a wide range of pro-inflammatory structural cells
This reduces infiltration of the lung by eosinophils and other cells that execute the exaggerated immune response
Increase expression of β2 receptors
Increase anti-inflammatory ILs which induce apoptosis in many inflammatory cells and reduce the number of mast cells in respiratory mucosa
Overall, reduce inflammation
Benefits of inhaled corticosteroids?
Improve symptoms
Improve lung function
Reduce exacerbations
Prevent death
