Asthma/COPD

Question 1

Name 4 examples of inhaled corticosteroids

Answer 1

Beclomethasone, Fluticasone, Mometasone, Budesonide

Question 2

Genomic mechanism of action of corticosteroids

Answer 2

C are lipophilic and are carried by corticoid binding globulins (CBG) in the plasma
They cross the cell membrane easily and binds to glucocorticoid-receptors which are nuclear receptors
G-receptors are bound to heat shock proteins at rest, and when the GC binds, the heat shock proteins dissociate
2 G-receptor complexes form a homodimer which translocates into the cell to bind to glucocorticoid response element (GRE) leading to upregulation of gene expression and protein synthesis

Question 3

Different genomic mechanism of action of corticosteroids

Answer 3

1) Formation of homodimer

2) Monomer binding to co-activator / co-repressor

Question 4

Anti-inflammatory action of ICS

Answer 4

1) Dec T cells, eosinophils and mast cells
2) Dec release of cytokines (IL-4, IL-5, IL-13) and chemokines (RANTES, eotaxin)
3) Dec mucus secretion and plasma exudation
4) Dec shedding of epithelial cells
5) Inc macrophage efferocytosis > resolution of inflammation
6) Inc expression of Annexin-1 (inhibitor of PLA2)
7) Dec expression of PLA2, 5-LOX and COX > dec in leukotrienes and prostanoids
8) Inc expression of Beta 2 agonist receptors in smooth muscle cells > potentiating the effects of beta 2 agonists

Question 5

Indications for use of ICS

Answer 5

1) 1st line asthma controller

2) Nocturnal asthma

Question 6

Clinical efficacy of ICS?

Answer 6

Does not relax the airways directly

1) Dec airway hyperresponsiveness over a few weeks
2) Dec frequency of exacerbation
3) Possibly reduces airway remodelling
4) Dec the use of beta agonist
5) Dec risk of asthma related deaths

Question 7

Side effects of ICS

Answer 7

1) Cough/throat irritation (no point)
2) Hoarseness of voice/croaky voice
3) Oropharyngeal candidiasis (instruct pt to rinse mouth after)
4) Hypothalamus-pituitary-adrenal axis suppression
5) Osteoporosis
6) Reduce growth velocity

Question 8

Side effects of ICS particularly in the elderly?

Answer 8

1) Glaucoma
2) Cataract
3) Easy bruising (dec collagen/keratin)
4) Hyperglycaemia/DM
5) Inc risk of opportunistic infection

Question 9

What is LTRA? Name an example

Answer 9

Leukotriene receptor antagonist

Montelukast

Question 10

What is the mechanism of action of LTRA?

Answer 10

Blocks the action of LTD4 (potent bronchoconstriction)

Question 11

Effects of LTRA?

Answer 11

1) Dec airway inflammation by
a) red T cells, eosinophils and mast cells
b) red Th2 cell responses and cytokines and chemokines
c) dec dendritic cells involvement and activation

2) Dec mucus hypersecretion by dec mucus production and goblet cells
3) Dec airway remodelling by blocking fibrolasts and inhibiting collagen release
4) Dec contractility and proliferation of smooth muscle cells in airways > dec bronchoconstriction
5) Dec vascular permeability in epithelial cells, dec mucosal edema

Question 12

Indications of LTRA?

Answer 12

1) Prophylaxis and control of asthma
2) Aspirin-induced asthma (due to inc AA substrate for 5-LOX pathway)
3) Exercise-induced asthma

Question 13

Clinical efficacy of LTRA?

Answer 13

Less effective than ICS

1) Dec airway inflammation
2) Dec peripheral blood eosinophil levels
3) Dec frequency of exacerbation
4) Dec airway remodelling
5) Inc lung function
6) Red use of ICS and beta 2 agonist

Question 14

Side effects of Montelukast?

Answer 14

Headache
Fever
Sore throat 
Stomach upset 
Diarrhoea 

Rare psych: 
Agitation 
Hallucination
Depression
Suicidal ideation