Bronchodilators Flashcards
Why are bronchodilators so effective in decreasing air ways resistance?
R is inversely proportional to radius, so a small change in radius has a very large impact on resistance. When bronchial radius is halved, airways resistance (R) is increased 16-fold.
Just a reminder of the whole picture
What class of Beta-agonists are short acting?
And what’s an example?
SABAs (short acting beta agonist) (known as relievers).
Salbutamol.
How do Beta2 agonists work?
What are their effects on airways smooth muscle
What are their effects on on epithelial cAMP?
MOA: Beta2 agonists increase intracellular cAMP, which activates PKA. This increases the conductance of Ca2+-sensitive K+ (K+Ca) channels in airways smooth muscle, this causes hyperpolarisation and relaxation (thereby inhibiting bronchial constriction).
Effects on B2-agonists on epithelial cAMP: Increased cAMP increases ciliary beat frequency, which improves mucous and allergen clearance.
In LABAs, what are the effects of B2 agonists on airways inflammatory cells?
And why do different patients show variability in response to B2 agonists?
By increasing cAMP, B2 agonists are thought to reduce the release of inflammatory mediators and cytokines (from mast cells, basophils, eosinophilhs, neutrophils & lymphocytes).
(No evidence however that chronic exposure to B2 agonists acutally reduces airways inflammation.
Patient response may vary due to polymorphisms in nucleotide sequence encoding for B2 receptor.
*Probably won’t come up since it’s no in a red box, but nice to know*
What class of b2 agonists is salbutamol?
What is its major effect
How is it administered?
How long does it take to work, and ho
What are the ADRs of B2 agonists?
(At high doses with acute or short term dosing)
- Tremor in peripheral skeletal muscle, due to activation of skeletal muscle B2 receptors
- Increased heart rate & force of contraction
- Can still affect B2 receptors in heart (loss of selectivity)
- B2-receptors interaction dilates peripheral vessels, this decreases diastolic BP, and may cause reflex tachycardia
-
Hypokalaemia (Causes hyperexcitability in myocardium)
- Stimulation of B2-adrenoreceptors in liver & skeletal muscle increases Na+K+ ATPase activty - this increases K+ uptake into cells from plasma.
What drug needs to be avoided when using B2 agonists?
Beta blocks (propranolol)
*
What are some examples of LABAs?
And why are these long acting?
Do they produce rapid relief?
When are they used?
What is the onset of action, peak effect, and bronchodialatory effect?
Salmeterol, Formoterol: (Long acting beta agonists)
And why are these long acting?
They have lipophilic side-chains which resist degradation, this prolonges their half life.
they do NOT produce rapid relief (except for formoterol)
They are used for nocturnal asthma, and exercise induced asthma
What is the onset of action, peak effect, and bronchodialatory effect?
- Onset of action is ~10-20 mins
- peak effect is ~1-2hours
- bronchodilatory effect is ~12hours
- Dosing is given in regular, twice dail
Should LABAs be used as a reliever?
What type of beta agonists should be used for rapid relief?
Do LABAs treat the underlying inflammation
LABAs shouldnt be used as a relive (not approved as rescue inhaler)
- Need to use SABAs for rapid relief, since they are short acting
- LABAs don’t treat underlying inflammation, *CANNOT be used without anti-inflammatories*
- Using beta agonist without anti-inflammatories just means you are masking the damage to the lungs.
- What are the benefits of a fixed dose combination inhaler?
- What is an example of a LABA + corticosteroid combination
- Using LABA with steroid allows the steroid dose to be reduced.
- Adjunctive role as prophylactic (given with inhaled glucocorticoids eg. fluticasone) gives better control of asthma
-
Seretide (Salmeterol and fluticasone)
- there are better outcomes when in combination
- or there’s symbicort (Budesonide and formoterol).
- What type of drug is ipratropium
- How is it taken
- What does it do
- What’s it’s onet
- Whats it’s duration
- Can be given with ______ to get an additive effect
What conditions is it used in?
- Ipratropium is a muscarinic receptor blocker
- Taken via inhaltion route
- It blocks the effects of parasympethic stimulation by blocking muscarinic receptors
- Has an onset of 30+ mins
- Duration is 3-5 hours
- Give with B2 agonist to have an additive effect
Ipratropium can be beneficial in acute asthma, most useful in COPD, and used for emphysema
Why do we just adjunct magnesium sulphate IV in acute severe asthma?
- Mg2+ decreases Ach release at the motor end plate on bronchial smooth muscle.
- Mg2+ is a “physiological Ca2+ anatagonist”
- Increases adenyl cyclase production of cAMP
- Mg2+ may be useful if has been epleted by frusemide, disease etc
What is theophylline?
MOA
Class of drug
- Its a PDE5 inhibitor
- Inhibits cAMP degradation, increasing bronchial smooth muscle relaxtion
- Inhibits PDE5 in lymphocytes and eosinophils, this improves asthma control
- Also is an antagonist for adenosine receptor (need to be very high dose to cause this)
- but no signficant effect on airways SM and mast cells
It’s a methylxanthine
What are the metabolism and pharmokinetics of theophylline?
- Mainly metabolised through CYP1A2 % CYP2E1
- CYP1A2
- CYP1A2 is induced by cigarette smoking, char-grilled meat, brussel sprouts -> this decreases theophylline blood levels
- CYP1A2 is inhibited by cimetidine, and Quinolone antibiotics (ciprofloxacin, norfloxacin) -> these theophylline blood levels
- CYP1A2
