Pharmacology of Airway Diseases

Question 1

What are the phases that drugs can target in COPD/Asthma?

Answer 1

Bronchoconstriction
Airway hyper-sensitivity/hyper-responsiveness
Airway inflammation

Question 2

What does the BAM mneumonic stand for?

Answer 2

Treatment of bronchoconstriction:
B2 adrenoceptor agonists
Anticholinergics
Methylxanthines

Question 3

What does the OSHIT nmeunomic stand for?

Answer 3

Acute asthma attack treatment 
Oxygen
Salbutamol
Hydrocortisone
Ipratropium 
Theophylline

Question 4

What does the Lu-Glu mnemonic stand for?

Answer 4

Anti-inflammatory treatment
Leukotriene receptor antagonists
Glucocorticoids

Question 5

Which nervous systems drive bronchodilator and bronchoconstriction?

Answer 5

Sympathetic -> bronchodilation (adrenergic nerve fibres and NA) eg B2 agonists facilitate dilation/relaxation

Parasympathetic -> bronchoconstriction (cholinergic nerve fibres and ACh) eg anticholinergics cause relaxation

Question 6

What’s the cell signalling pathway of B2 adrenoceptor stimulation?

Answer 6

GPCR -> B2 agonist binding activates Gs g-protein
Gs activates AC -> cAMP -> PKA (reduces activity of MLCK by dephosphorylating MLC and reduces intracellular Ca2+ to reduce smooth muscle contraction)

Question 7

What are side effects of B2 agonists?

Salbumatol & Terbulatine, Formoterol & Salmeterol

Answer 7

Tremor, tachycardia, cardiac arrhythmias

Question 8

What’s the cell signalling MOA of anticholinergics?

Answer 8

M3 mAChR - Gq protein activation -> PLC -> IP3 -> increase intracellular Ca2+ release for contraction

Anticholinergics BLOCK M3 to reduce smooth muscle contraction

Question 9

What are side effects of anticholinergics?

Answer 9

Dry mouth, constipation, urinary retention

Question 10

What’s the MOA of Methylxanthines? Side effects?

Answer 10

Act on B2 adrenoceptors
cAMP -> PKA usually inactivated by PDE
Methylxanthines inhibit PDE to sustain PKA actions = reduce intracellular Ca2+ to reduce smooth muscle contraction

Very toxic cardiac and neurologic effects (seizures) so carefully controlled

Question 11

Where are leukotriene receptors found and what are their actions?

Answer 11

Eosinophils - guide chemotaxis to sites of inflammation

Bronchiolar smooth muscle cells - smooth muscle contraction via PLC activation

Question 12

What’s the MOA of leukotriene receptor antagonists?

Answer 12

Block CysLT1 on eosinophils -> reduce inflammatory responses (good as a preventer or when used in addition to glucocorticoids)

Side effect = abdominal pain, headache

Question 13

What’s the MOA of glucocorticoids and their side effects?

Answer 13

Diffuse through membrane, bind to intracellular glucocorticoid receptor which interacts with selective DNA sequences to influence expression of genes

Suppression of pro-inflammatory mediators (cytokines)
Express anti-inflammatory mediators and upregulate B2 adrenoceptors

Side effects: moon face, weight gain, osteoporosis, hyperglycaemia