Pharmacology: Pharmacology of airway control Flashcards
What is the pathophysiology of asthma?
Restricted airway flow via
1. Mucosal oedema
2. Bronchoconstriction due to bronchospasm
3. Mucus plugging
Eventually leads to airway remodelling and bronchial hyperresponsiveness
What are the main classes of drugs used to treat asthma?
Give examples
- B2 agonists to target smooth muscle (salbutamol, salmeterol)
- steroids to reduce inflammation (inhaled budesonide, oral prednisolone)
Asthma is treated in a stepwise approach, what is classed as good asthma control?
- minimal symptoms
- minimal need for reliever medication
- no exacerbations
- no limitation of physical activity
- normal lung function
What is a ‘step 1’ asthmatic patient?
A person with mild intermittent asthma
Managed with short acting B2 antagonist on an as-required basis, if used regularly they should step up
What is the effect of B2 agonists?
Predominant action is inhibition of bronchoconstriction on airway smooth muscle
If used intermittently can inhibit mast cell degranulation but on regular use can actually increase mast cell degranulation
What is the intracellular mechanism of action of B2 agonists?
Bind to B2 adrenoreceptor which is a GPCR
Gs protein dissociates and activates adenyl cyclase which causes increased cAMP which activates protein kinase A and inhibits myosin light chain kinase, this promotes relaxation and inhibits contraction
What are the side effects of B2 agonists?
Predictable due to adrenergic effects
- tachycardia, palpitations, tremor
What are the guidelines to step up to an inhaled corticosteroid?
Per week:
- using B2 agonist 3 times or more
- symptoms 3x
- nocturnal waking at least once a week (sign of poorly controlled asthma)
- consider if exacerbation in last 2 years requiring oral steroids
What are the benefits of inhaled corticosteroids?
- improve symptoms
- improve lung function
- reduce exacerbations
- prevent death
What is the molecular action of steroids?
Pass through membrane and bind to IC receptor
Steroid-receptor complex enters nucleus and binds to DNA
1. Transactivation: increases activation of anti-inflammatory proteins, upregulates B receptors
2. Transpression: prevents translation of the pro-inflammatory proteins
How do inhaled drugs enter the systemic circulation?
Can enter the systemic circulation from the lungs
Some can be swallowed and metabolised through the liver.
At high doses drugs such as bleclomethasone and fluticasone can cause systemic side effects
Which asthmatic patients respond better to oral inhaled steroids?
Eosinophilic asthma
What checks need to be done before initiating a new drug treatment eg stepping up?
- check patients compliance
- check inhaler technique
- eliminate triggers
List the classes of medications used for asthma in order
Give first: SABA eg salbutamol, terbutaline
Oral inhaled steroid (dose not increased as next step as majority of actions is at low doses)
LABA eg salmeterol, formoterol (must always be prescribed with a steroid because they are not anti-inflammatory)
Why are LABA and inhaled corticosteroid steroids combined in one inhaler?
- simpler for patients
- compliance
- only 1 prescription to organise
- potentially cheaper
- SAFETY, cannot take LABA without steroid which would be DANGEROUS