Respiratory: Asthma Flashcards
What drugs act as bronchodilatorys
SABAs
LABAs
CystLT1 receptor antagonists
xanthines
What drugs act as controllers? ie anti inflammatory
glucocorticoids
Chromoglicate
Monoclonal antibodies
Xanthines
What g protein couples with beta 2 adrenoceptors?
Gs
What does agonisation of beta 2 result in
Activates adenyly cyclase and increases cAMP production
What does increases cAMP mean in broncho smooth muscle
Increase protein kinase A
Phosphorylates MLCK
RELAXATION
What two kinases are involved in beta 2 adrenoceptor desensitization and endocytosis?
Protein kinase A
G protein receptor
Describe the endosytosis of beta adrenoceptors
Receptor phosphorylated by GRL B arrestin binds to resceptor Becomes a vesicle within the cell Endosome= recycled Lysosome= degraded
How long do SABA effects last?
30 mins= maximal effect
lasts 4-6 hours
What are the side effects of SABAs?
Fine tremor
Occasional tachycardia
How do CysLT1 receptor antagonists work?
Competitively block CysLT1 receptor.
Cyst LTs come from mast cell degranulation and inflammatory cells and cause bronchoconstriction by acting on CysLT1 receptors
This is blocked using Cyst LT1 antagonists
What encourages the release of LTA4 from mast cells?
Mast cell activation causes intracellular release of arachidonic acid by phospholipase A2.
This stimulates FLAP which releases LTA
When are CysLT1s used?
Add on therapy in mild persistant asthma.
Good for both allergic and exercise asthma
Name two cystLT1 receptor antagonist?
Montelukast
Zafirlukast
Name two xanthines?
Aminophylline and theophylline
How do glucocorticoids signal ?
Via nuclear receptors
What do glucocorticoids bind to within the cytoplasm?
GR alpha
How are glucocorticoids taken up into the nucleus?
By importins
What happens to glucocorticoids in the nucleus?
The activated receptors bind assemble to homodimers and bind to GrE in the promotor region
Certain genese are swithed on or off
How are inflammatory genes expressed?
Associated with acetylation of histones by histone acetyltransferases.
How do glucocorticoids switch off inflammatory genes?
Recruit histone deacetylases
What effects to glucocorticoids have that are relevent to asthma?
Decrease Th2 production Cause apoptosis Decrease eosinophils Prevent IgE production Decrease number of mast cells and decrease FcE expression
What are the advese affects of glucocorticoids?
Dysphonia
Oropharyngeal candidiasis
Name a cromolin
Sodium cromoglicate
