11. Asthma drugs Flashcards
Which drug would you prescribe to an asthmatic P suffering only from infrequent, short-lived wheezes?
SABA (as required)
Which drugs would you prescribe to an asthmatic P having to use SABA 3+/week (different steps of management)?
Step 1: SABA (e.g. salbutamol, terbutaline) as required
Step 2: low dose ICS (beclomethasone)
Step 3: LABA (e.g. formoterol, salmeterol) + low dose ICS (can increase dose if unresponsive)
Step 4: LABA + high dose ICS OR LTRA (e.g. montelukast) / aminophylline
Step 5: daily oral steroid + high dose ICS + consider others
SABA as required at all steps.
Which size particles should inhaler devices use? Explain why.
- 1-5 micron particles = optimal size for deposition in small airways
- 10 micron particles are too large - deposited in mouth and oropharynx
- 0.5 micron particles are too small - inhaled into alveoli and exhaled without deposition
What are SABAs used for? Explain their MOA.
Used for:
- symptom relief as required
- prevention of bronchoconstriction, e.g. on exercise
Act at beta2 Rs on airway smooth muscle to promote bronchodilation.
Why should SABAs not be regularly used?
Regular use increases mast cell degranulation in response to allergens - decreases asthma control.
What are the possible ADRs of SABAs?
Are adrenergic so can cause tachycardia, palpitations, tremors, etc. by acting at other B adrenoRs.
How are LABAs different to SABAs? What are these used for?
Have the same MOA but have long duration of action.
Used to:
- improve asthma symptoms
- improve lung function
- reduce asthma exacerbations
What must LABAs always be prescribed in conjunction with? Why?
With ICSs as LABAs are not anti-inflammatory on their own.
What are ICSs used for? What is their MOA?
Used in EOSINOPHILIC ASTHMA Ps to:
- improve symptoms
- improve lung function
- reduce exacerbations
- prevent death
Act as anti-inflammatory agents: bind to cytoplasmic alpha glucorticoid Rs causing chaperone dissociation… complex act in:
- transactivation: activate transcription of beta2 R genes and anti-inflammatory molecule genes
- transrepression: inhibit nuclear translocation of pro-inflammatory transcription factors
Why can ICSs cause systemic side effects?
Even though inhaled, ICSs have potential to reach systemic circulation as:
- small fraction is swallowed, absorbed in gut, reaches liver where some inactivated by 1st pass metabolism but some reaches systemic circulation
- small fraction absorbed directly from lungs to reach systemic circulation
But side effects are rare and usually only occur at higher doses.
When are leukotriene R antagonists used? What is their MOA?
As add-on therapy: some anti-asthma activity but only useful in about 15% of Ps.
Inhibit leukotriene R to block effects of leukotrienes (are released by mast cells and eosinophils can can induce bronchoconstriction, mucus secretion, mucosal oedema and promote inflammatory cell recruitement).
When are methylxanthines used and what is their MOA?
Add on therapy in severe asthma (often poorly efficacious).
Antagonise adenosine R.
When are long-acting anti-cholinergics used and what is their MOA?
Licensed for COPD and severe asthma:
- reduce exacerbations
- small improvement in lung function and symptoms
Promote bronchodilation via M3 R inhibition.
Name 3 possible ADRs of long-acting anti-cholinergics.
- dry mouth
- glaucoma
- urinary retention
A P presents to AandE with acute severe asthma. How would you manage this?
- High flow oxygen (aim for O2 sats 94-98%)
- Nebulised salbutamol
- Oral prednisolone
- Nebulised ipratropium bromide
- Consider IV aminophylline if no improvement with life-threatening features.
