Asthma

Question 1

What is the primary mechanism of action of salbutamol?

Answer 1

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

Question 2

What does salbutamol act on?

Answer 2

Beta 2 (β2) adrenergic receptor

Question 3

What are the side effects of salbutamol?

Answer 3

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

Question 4

Why can cardiac side effects of salbutamol be seen?

Answer 4

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

Question 5

What can exacerbate the hypokalaemia seen with patients given salbutamol?

Answer 5

Hypokalaemia can be caused via an effect on sodium/ potassium ATPase. This effect can be exacerbated by coadministration with corticosteroids

Question 6

What is the mechanism of action of Fluticasone?

Answer 6

Fluticasone directly decreases inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells. It reduces the number of these cells and also the number of cytokines they produce

Question 7

What is the drug target of Fluticasone?

Answer 7

Glucocorticoid receptor

Question 8

What are the local side effects of Fluticasone?

Answer 8

Sore throat, hoarse voice, opportunistic oral infections

Question 9

What is the relevance of Fluticasone having a low bioavailability?

Answer 9

Oral bioavailability <1%. Therefore, any systemic delivery via the inhaled route is predominantly through the pulmonary vasculature.

Question 10

What is mometasone similar to?

Answer 10

Fluticasone and Budesonide

Question 11

Which is the least potent between Mometasone, Fluticasone and Budesonide?

Answer 11

Budensonide

Question 12

What is the bioavailability of Budesonide and what are the implications of this?

Answer 12

Oral bioavailability >10%. Therefore, inhaled budesonide will still result in some systemic absorption through the gastro-intestinal tract.

Question 13

What is the mechanism of action of Montelukast?

Answer 13

Antagonism of CysLT1 leukotriene receptor on eosinophils, mast cells and airway smooth muscle cells decreases eosinophil migration, broncho-constriction and inflammation induced oedema

Question 14

What is the drug target of montelukast?

Answer 14

CysLT1 leukotriene receptor

Question 15

What are the side effects of montelukast?

Answer 15

Mild side effects:
Diarrhoea
Fever
Headaches
Nausea or vomiting

Serious side effects:
Mood changes
Anaphylaxis

Question 16

How long should you wait before doing exercise when giving Montelukast as prophylaxis of exercise-induced bronchoconstriction?

Answer 16

wait 2 hours before initiating exercise.

Question 17

Why is salbutamol inhalation preferred over oral?

Answer 17

Faster action

Reduced systemic side effects

Easier

Inhaled dose 10x smaller than oral dose

LOCAL VS SYSTEMIC

Question 18

Only 20% of the inhaled salbutamol gets to the lungs - where does the rest go?

Answer 18

1. EXHALED
2. ABSORPTION FROM LUNGS
3. MUCOCILIARY CLEARANCE
4. ORAL SWALLOWED
5. ABSORBED THROUGH MUCOUS MEMBRANE IN ORAL CAVITY AND PHARYNX

Question 19

What is the mechanism of action for montelukast and why might it be particularly useful for NSAID (Non-steroidal anti-inflammatory drug)-induced asthma?

Answer 19

When medications such as NSAIDs or aspirin block the COX-1 enzyme, production of thromboxane and some anti-inflammatory prostaglandins is decreased, and in patients with aspirin-induced asthma, this results in theoverproduction ofpro-inflammatory leukotrienes, which can cause severe exacerbations of asthma

Montelukast works by inhibiting the leukotriene receptor