Asthma drugs

Question 1

Describe the mechanism of action of B2 agonists for the treatment of asthma/bronchoconstriction

Answer 1

Bind Gs coupled protein –> stimulate adenylate cyclase –> increase cAMP in bronchial smooth muscle cells –> activates protein kinase A –> inactivates MLCK and activates MLCP –> dephosphorylation MLC –> Smooth muscle relaxation –> bronchodilatation

E.g. adrenalin/salbutamol

Question 2

Describe the mechanism of action of antimuscarinic agents in the management of asthma/bronchospasm

Answer 2

Antagonism of M3 receptors in bronchial smooth muscle –> Inhibition Gq protein coupled receptor –> reduced IP3 and DAG –> Decrease cyclic GMP –> reduce activation Phospholipase C –> Reduced intracellular calcium –> Smooth muscle relaxation

Question 3

Which enantiomer of salbutamol is more effective

Answer 3

R-enantiomer

Question 4

Describe the mechanism of action of corticosteroids in the treatment of asthma

Answer 4

Cytosolic receptor forms a dimer with the steroid which then moves into the cell nucleus –> regulation of gene transcription –> Downregulates synthesis of cyclo-oxygenase and phospholipase –> reduced inflammatory mediators

Question 5

Name two methylxanthines and describe their mechanism of action

Answer 5

Theophylline
Aminophylline

These are non-selective adenosine receptor antagonists.

BUT

MOA in asthma is Non-selective PDE inhibition –> Increase cAMP in bronchial smooth muscle –> Reduced activation of protein kinase A –> Inhibition MLCK and activation of MLCP –> smooth muscle relaxation.

Low potency, high toxicity

Question 6

Describe the mechanism of action of MgSO4 in the treatment of bronchospasm

Answer 6

Antagonists of calcium at the NMDA receptor-gated calcium channels –> smooth muscle relaxation.

Inhibits Ach and histamine release

Low potency, low efficacy, low toxicity

Question 7

Describe the mechanism of action of ketamine in the treatment of bronchospasm

Answer 7

NMDA receptor antagonist –> reduced intracellular calcium

Also NMDA receptor independent bronchodilatation: Interferes with calcium dependent step in histamine induced bronchoconstriction

Question 8

Describe the mechanism of action of volatile anaesthetics in the treatment of bronchospasm

Answer 8

Decreased IC Calcium by and unknown mechanism ? onhibitionof IP# induced calcium release.

Question 9

How do Helium-oxygen mixtures aid in the treatment of bronchospasm?

Answer 9

Decrease density of inspired gases
Decreases Reynolds number –> decreased likelihood of turbulent flow at any given flow rate and promotes laminar flow which is usually associated with lower resistance. The use of helium decreases the respiratory resistance in bronchospasm

Also improves gas exchange and the distal delivery of nebulized medications