Pharmacology of Asthma

Question 1

What is the mechanism of action of Salbutimol?

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 is the drug target for Salbutimol?

Answer 2

Beta 2 (β2) adrenergic receptor

Question 3

What are the main side effects of Salbutimol?

Answer 3

Palpitations/ agitation

Tachycardia/ Arrythmias

Hypokalaemia (at higher doses)



Question 4

What is Salbutimol’s half life?

Answer 4

Salbutamol is a short acting beta agonist (SABA). It’s half life is 2.5-5hours.

Question 5

How do you get cardiac effects from Salbutimol?

Answer 5

Beta 2 selectivity is not absolute, so you can get some beta 1 (cardiac effects).

Question 6

How do you get Hypokalaemia from Salbutimol?

Answer 6

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

Question 7

What is the mechanism of action of Fluticasone, Mometasone, Budenoside?

Answer 7

Multiple actions on many different cell types. 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 8

What is the target of Fluticasone, Mometasone, Budesonide?

Answer 8

Glucocorticoid receptor - greater affinity than cortisol

Question 9

What are local side effects of Fluticasone, Mometasone, Budesonide?

Answer 9

Sore throat, hoarse voice, opportunistic oral infections



Question 10

What are systemic side effects of Fluticasone, Mometasone, Budesonide?

Answer 10

Growth retardation in children

Hyperglycaemia

Decreased bone mineral density

Immunosuppression

Effects on mood

(Many others)

Question 11

How is Fluticasone, Mometasone systematically delivered?

Answer 11

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

Question 12

How is Budesonide systematically delivered?

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 least potent out of Fluticasone, Mometasone & Budesonide

Answer 13

Budesonide

Question 14

What is the mechanism of action of Montelukast?

Answer 14

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

Question 15

What is the target for Montelukast?

Answer 15

CysLT1 leukotriene receptor

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

When should Montelukast be administered prior to exercise?

Answer 17

For prophylaxis of exercise-induced bronchoconstriction, montelukast should be administered at least 2 hours before initiating exercise.

Question 18

Why is the inhalation route preferred to the oral route when using Salbutimol?

Answer 18

Local delivery as opposed to systemic - localised to the target organ allowing lower doses than is necessary in systemic delivery

Question 19

How can asthma be exacerbated by viral infections?

Answer 19

viral infection releases mediators that activate eosinophils specifically, eosinophils induce epithelial damage due to release of a major basic protein, increasing susceptibility to viral infections.