2- therapeutics of obstructive airway disease Flashcards
what do the preventer/controller drugs do?
anti-inflammatory
what are the reliever drugs mechanisms (rough)?
bronchodilators
what bronchodilators prescribed?
beta 2 agonists, muscarinic antagonists
why do muscarinic antagonists bronchodilate?
post ganglionic parasympathetic release acetylcholine that acts on muscarinic receptors to make bronchoconstriction = so muscarinic antagonist medication
*M3 receptors are what is being acted on - they are Gq proteins so phosphorylate Ca2+ via phospholipase C etc so bronchoconstriction
why is it better to give drugs that act further up inflammatory cascade rather than just salbutamol to make muscles feel better once cascade already occurred?
airway smooth muscle is twitchy and hypersensitive - because sensitised by inflammatory cascade activated from above = so want to damp down inflammatory cascade from above to prevent twitchy smooth muscle in first place
→one of key treatment goals of asthma should be patient requires hardly any or if at all beta 2 agonists (like salbutamol)
if twitchy smooth muscle and needs a lot of salbutamol, its not under control and need to make higher dose of getting type 2 inflammation under control
what are they type 2 biomarkers?
- eosinophils = IL5
- IgE = IL 4
- FeNO = IL13
what is the pyramid for asthma treatment?
- reliever = short acting beta agonist (salbutamol)
- 1st line controller = inhaled corticosteroid
- 2nd line controller is addition to 1st line = long acting beta agonist, long acting muscarinic antagonists, leukotriene blocker receptor antagonist, theophylline (in order)
- short term oral corticosteroids (long term has bad effects like rheumatoid, immunosuppression), long term use biologics (monoclonal antibodies) which are more targeted & precise so less side effects so long term
what is bad about oral corticosteroids? (why only used for longterm)
suppress cytokines 4,5,13 (type 2) but also suppress type 1 cytokines (1,6, tnf alpha) which makes problems like rheumatoid etc etc
= just suppress like everything
what is new 2nd track way of guidelines for asthma where reliever & controller in one inhaler?
- patients perceive benefits of salbutamol as faster acting whereas steroid diffuses into cell membrane and onto nucleus which means people overuse blue inhaler and underuse brown so you just suppress the pain and not treating underlying problem
- 1 inhaler good as means that people can’t uncouple use of reliever (blue) & controller (brown) hence why in top table the preferred reliever has low dose ICS-formoterol
= use more when you need it and less when you don’t
what is important corticosteroid?
BDP (Beclometasone dipropionate)
why can corticosteroids cause pneumonia in COPD?
because corticosteroids suppress lots due to local immune suppression & impaired mucociliary clearance
& altered microbiome
what is an example of oral corticosteroid that can only be given short term?
prednisolone
is corticosteroids used as monotherapy or combination?
monotherapy or combination for asthma
only in combination for COPD
how does steroid affect the peak flow and diurnal variation?
the average value improves and amplitude of diurnal variation become smaller (attenuated)
what is function of spacer device?
particles go into spacer and slows down and makes particles smaller which means will travel further into lungs = improves lung deposition
large particles get left in chamber (inhaler without spacer means large particles get left on vocal cords etc and cause problems like oropharyngeal & laryngeal side effects), also can get thinning of muscle in vocal cords = hoarseness so never use without spacer device
what are breath actuated inhalers?
twist base to activate dry powder and you suck in and de-aggregates dry powder (automatically works when breathe in = no pressing on inhaler)
problem = can’t use with spacer so can get side effects but is easier to use
