Asthma

Question 1

Describe the primary mechanism of action of salbutamol (SABA).

Answer 1

1. Agonist at the β2 receptor on airway smooth muscle cells.
2. Activation reduces Ca2+ entry and this prevents smooth muscle contraction.

Question 2

What does salbutamol target?

Answer 2

Beta 2 (β2) adrenergic receptor

Question 3

What are the main side effects of Salbutamol?

Answer 3

• Palpitations/ agitation
• Tachycardia/ Arrythmias
• Hypokalaemia (at higher doses)

Question 4

How does Salbutamol cause cause cardiac effects?

Answer 4

Beta 2 selectivity is not absolute – as a result, cardiac (beta 1) effects can be seen.

Question 5

How does Salbutamol cause Hypokalaemia?

Answer 5

Salbutamol can effect sodium/ potassium ATPase in the liver and muscles.

Question 6

Name some inhaled corticosteroids that can be prescribed to people with asthma.

Answer 6

• Fluticasone
• Mometasone
• Budesonide

Question 7

Describe the mechanism of action of these corticosteroids.

Answer 7

1. Binds to glucocorticoid receptor which is inside the cell in many cells like eosinophils/mast cells/ T lymphocytes.
2. They reduce release of inflammatory cytokines like IL-5 which reduce eosinophilic inflammation.

Question 8

What is the target site of these corticosteroids?

Answer 8

Glucocorticoid receptor within inflammatory cells like eosinophils (steroids are lipid soluble so they can pass through the membrane)

Question 9

What are the local side effects of these corticosteroids?

Answer 9

• Sore throat
• hoarse voice
• opportunistic oral infections

Question 10

What are the systemic side effects of these corticosteroids?

Answer 10

• Growth retardation in children (it is a steroid)
• Hyperglycaemia
• Decreased bone mineral density
• Immunosuppression
• Effects on mood

Question 11

Describe the oral bio-availablility of fluticasone + Mometasone, and compare it to that of salbutamol. What does it mean for the systemic delivery of fluticasone + Mometasone ?

Answer 11

• < 1% for fluticasone/ Mometasone because of first pass metabolism in the liver. This means that any systemic delivery will occur predominantly through the pulmonary vasculature.
• Salbutamol is more bio-available as it doesn’t get metabolised as much by the liver when it enters the blood.

Question 12

Describe the oral bio-availability of Budesonide and what does this mean for the systemic delivery of the drug?

Answer 12

> 10%

This means that inhaled budesonide will still result in some systemic absorption through the GI tract.

Question 13

Which of these corticosteroids is the least potent?

Answer 13

Budesonide

Question 14

Describe the mechanism of action of Montelukast and what are the effects of the drug?

Answer 14

CysLT1 leukotriene receptor antagonist.
It decreases..
- eosinophil migration
- broncho-constriction
- inflammation induced oedema

Question 15

Describe the target site of Montelukast.

Answer 15

CysLT1 leukotriene receptor on

• airway smooth muscle cells
• eosinophils
• mast cells

Question 16

What are the side effects of Montelukast?

Answer 16

Mild side effects:

• Diarrhoea
• Fever
• Headaches
• Nausea or vomiting

Serious side effects:

• Mood changes
• Anaphylaxis

Question 17

What is Montelukast prescribed for?

Answer 17

• prophylaxis of exercise-induced bronchoconstriction/ asthma