Airway Control

Question 1

Understand autonomic innervation pharmacology of bronchial smooth muscle

Answer 1

Sympathetic:
B-adrenoceptors (B2) cause bronchodilation via decreased histamine release and increased mucociliary clearance
Parasympathetic:
M3 receptors maintain smooth muscle tone
Inhibitory/excitatory NANC innervation (neurotransmitters)

Question 2

Describe the main features underlying pathophysiology of asthma including that responsible for early and late phase response

Answer 2

Immediate phase - mast cell fixed IgE –> histamine release –> bronchospasm
Late phase - leucocytes –> epithelial damage, exacerbated bronchospasm and congestion
Thickening of BM, oedema, mucus
Bronchial hyperresponsiveness - an exaggerated bronchoconstrictor response to direct pharmacological stimuli (histamine) or indirect stimuli (e.g. exercise)

Question 3

Describe the action of short and long acting B2 agonists, ADRs and when they are used

Answer 3

MOA - Gs –> increased cAMP –> protein kinase A –> decreased intracellular calcium –> hyperpolarisation of muscle cells –> bronchodilation
Short acting e.g. salbutamol, terbutaline, formoterol
Long acting e.g. salmeterol, formoterol
ADRs - skeletal muscle tremor, tachycardia, dysrhytmia

Question 4

Describe the action of methylxanthines, ADRs and when they are used

Answer 4

E.g. theophylline, aminophylline
MOA - adenosine receptor antagonist –> bronchodilation
ADRs - psychomotor retardation, tachycardia

Question 5

Describe the action of muscarinic receptor antagonists, ADRs and when they are used

Answer 5

E.g. ipratroprium, tiotropium
MOA - bind to M3 receptor –> blocks constricting effects of ACh, inhibits mucus secretion
ADRs - dizziness, dry mouth
*Not first line in asthma, used in COPD

Question 6

Understand the broad mechanism of anti-inflammatory action of the corticosteroids and ADRs

Answer 6

E.g. prednisolone
MOA - suppress gene transcription in pro inflammatory cells, decrease eosinophil lung infiltration, increase B2 receptors, anti-inflammatory IL, induce apoptosis of inflammatory cells, decreased mast cells
ADRs - croaky voice, sore throat, oral thrush

Question 7

Outline the general steps in management of asthma

Answer 7

Stepwise Approach to Dosing in BNF: minimises effect of long term high dose glucocorticoids
Step 1 - SABA
Step 2 - + ICS
Step 3 - + LABA
Step 4 - + LRA/anti-muscarinic/methylxanthine
Step 5 - +oral steroid/IgE

Question 8

Describe the steps in management of severe acute asthma

Answer 8

Supplementary oxygen to maintain SpO2 level of 94-98%
B2 agonist bronchodilators
Ipatropium bromide 
Corticosteroids
IV magnesium sulphate?