Asthma Flashcards
What are the short-term and long-term objectives for asthma treatment?
short term: relief
long term: prevention
In an asthma attack, what do the immediate and late phases comprise of?
immediate: bronchospasm
late: inflammation
Salbutamol is a _____ agonist
beta-2 adrenergic receptor
How does a B2 agonist work?
target
location
effect
target: B2 adrenergic receptor
location: bronchial smooth muscle
effect: reduced Ca2+ entry -> reduced smooth muscle contraction
bronchodilation
Fill in the blanks
Why is the inhalation route preferred over the oral route
fast acting
direct action
doesn’t undergo metabolisation in GI tract which can alter effect
more selective/specific (less side effects)
increased potency
more dose reaches target
Why is a nebulizer the best method for delivering salbutamol in an emergency situation?
Where can inhaled asthma drugs be lost?
There is a discrepancy between the expected dose and the actual dose. Why is a spacer clinically useful, especially in children?
more drug gets into lungs
Evidence suggests that only ____% of the inhaled dose of salbutamol (or any inhaled drug) penetrates deep enough into the lungs to be able to influence lung function (e.g. reduce breathlessness).
20%
What is the mechanism of action of fluticasone propionate in terms of reducing eosinophilic inflammation?
target, location, effect
target: glucocorticoid receptor (intracellular receptor)
location: eosinophil
effect: inhibition of IL5
IL-5critically regulates expression of genes involved in proliferation, cell survival and maturation and effector functions of B cells and eosinophils. Thus, IL-5 plays a pivotal role in innate and acquired immune responses and eosinophilia.
IL-5 essential for eosinophil proliferation, maturation and release into circulation
Why do common viral infections (e.g. rhinovirus) often exacerbate asthma?
they are known to release mediators that specifically activate eosinophils.
Eosiniophils can induce epithelial damage (e.g. due to release of major basic protein).
Like salbutamol, a significant proportion of inhaled fluticasone is actually swallowed. Despite this, the oral bioavailability (i.e. the proportion of drug that reaches the plasma VIA the gastrointestinal tract) is less than 1%. Why is this the case?
fluticasone: metabolised by liver very quickly into a product that is excreted quickly and has no effect on rest of body
Q6: What is the mechanism of action for montelukast and why might it be particularly useful for NSAID (Non-steroidal anti-inflammatory drug)-induced asthma?
target, location, effect
target: CysLT receptor
location: Eosinophils/mast cells/airway smooth muscle
effect: less smooth muscle constriction, eosinophil migration, edema
it is a selective leukotriene receptor antagonist (located in smooth muscle in airway)
- Leukotrienes causes broncho-constriction and airway oedema
- motelukast inhibits leukotriene receptor
- reduces inflammation
used specifically in NSAID-induced asthma
NSAIDs act on COX, which shifts the pathway to the leukotriene side, so more leukotrienes
therefore inhibits that receptor is useful in NSAID-induced asthma
lipooxygenases is not found everywhere (mostly in airways), so no systemic effect
How do NSAIDs work? Why may montelukast work for NSAID induced asthma?
NSAIDs act on COX, which shifts the pathway to the leukotriene side, so more leukotrienes
montelukast inhibits that receptor and is therefore useful in NSAID-induced asthma
