pharmacology of asthma

Question 1

primary mechanism of action of salbutamol

Answer 1

1) agonist at the beta 2 receptor on airway smooth muscle cells
2) Activation prevents calcium entry and this prevents smooth muscle contraction

Question 2

target for salbutamol

Answer 2

beta 2 adrenergic receptor

Question 3

Main side effects of salbutamol

Answer 3

Palpitations/ agitation

Tachycardia/ Arrythmias

Hypokalaemia (at higher doses)

Question 4

What type of bronchodilator is salbutamol

Answer 4

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

Question 5

Salbutamol selectivity for beta 2 is not

Answer 5

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

Question 6

Salbutamol effect on potassium

Answer 6

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

Question 7

Fluticasone, mometasone and budesonide mechanism of action

Answer 7

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

Targets for fluticasone mometasone and budesonide

Answer 8

glucocorticoid receptor

Question 9

Local side effects of fluticasone mometasone and budesonide

Answer 9

sore throat, hoarse voice, opportunistic throat infections

Question 10

Systemic side effects of fluticasone, mometasone and budesonide

Answer 10

growth retardation, hyperglycaemia, decreased bone mineral density, immunosuppression, mood effects

Question 11

Oral bioavailability of fluticasone, mometasone and budesonide

Answer 11

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

Question 12

fluticasone mometasone and budesonide have greater affinity for the glucocorticoid receptor compared to

Answer 12

cortisol

Question 13

Which of the following is the least potent: fluticasone, budesonide or mometasone

Answer 13

budesonide

Question 14

primary 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

target of montelukast

Answer 15

CysLT1 leukotriene receptor

Question 16

What can montelukast be used for specifically

Answer 16

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

Question 17

why is inhalation route preferred over oral route for

Answer 17

more rapid onset

smaller doses

Question 18

Advantages of using nebuliser

Answer 18

requires minimal patient co operation 
can deliver combinations 
many drug solutions 
concentration and dose can be modified 
normal breathing pattern

Question 19

Evidence suggests that only 20% of the inhaled dose of salbutamol (or any inhaled drug) penetrates deep enough into the lungs to be able to influence lung function (e.g. reduce breathlessness).

Q5. What do you think happens to the other 80% of inhaled salbutamol?

Answer 19

1) exhaled
2) mucociliary clearance
3) absorbed by mucous membranes in oral cavity and pharynx
4) absorbed into systemic circulation
5) absorbed into gut

Question 20

why is a spacer clinically useful

Answer 20

more salbutamol reaches lungs

Question 21

Like salbutamol, a significant proportion of inhaled fluticasone is actually swallowed. Despite this, the oral bioavailability (i.e. the proportion of drug that reaches the plasma VIA the gastrointestinal tract) is less than 1%. Why is this the case?

Answer 21

first pass inactivation in liver