Pharmacology of Asthma

Question 1

What are the 5 main asthma drugs?

Answer 1

1. Salbutamol
2. Fluticasone
3. Mometasone
4. Budesonide
5. Montelukast

Question 2

What is the primary mechanism of action of salbutamol?

Answer 2

Agonist at the β2 receptor on airway smooth muscle cells

Activation reduces Ca2+ entry and this prevents smooth muscle contraction

Question 3

What is the drug target site for salbutamol?

Answer 3

Beta 2 (β2) adrenergic receptor

Question 4

What are the main side effects of salbutamol?

Answer 4

Palpitations/ agitation

Tachycardia/ Arrythmias

Hypokalaemia (at higher doses)

Question 5

What is the primary mechanism of action of fluticasone?

Answer 5

Very powerful drugs - multiple actions on many different cell types

Fluticasone directly reduces the number of inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells = reduces the number of cytokines they produce

Question 6

What is the drug target site for fluticasone?

Answer 6

Glucocorticoid receptor

Question 7

What are the main side effects of fluticasone?

Answer 7

Local side effects:

Sore throat, hoarse voice, opportunistic oral infections

Systemic side effects:

Growth retardation in children
Hyperglycaemia
Decreased bone mineral density
Immunosuppression
Effects on mood



Question 8

What is the primary mechanism of action of mometasone?

Answer 8

Very powerful drugs - multiple actions on many different cell types

Mometasone directly reduces the number of inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells = reduces the number of cytokines they produce

Question 9

What is the drug target site for mometasone?

Answer 9

Glucocorticoid receptor

Question 10

What are the main side effects of mometasone?

Answer 10

Local side effects:

Sore throat, hoarse voice, opportunistic oral infections

Systemic side effects:

Growth retardation in children
Hyperglycaemia
Decreased bone mineral density
Immunosuppression
Effects on mood

Question 11

What is the primary mechanism of action of budesonide?

Answer 11

Very powerful drugs - multiple actions on many different cell types

Budesonide directly reduces the number of inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells = reduces the number of cytokines they produce

Question 12

What is the drug target site for budesonide?

Answer 12

Glucocorticoid receptor

Question 13

What are the main side effects of budesonide?

Answer 13

Local side effects:

Hoarse voice, opportunistic oral infections

Systemic side effects:

Growth retardation in children
Hyperglycaemia
Decreased bone mineral density
Immunosuppression
Effects on mood

Question 14

What is the drug target site for montelukast?

Answer 14

CysLT1 leukotriene receptor

Question 15

What are the main side effects of montelukast?

Answer 15

Mild side effects:

Diarrhoea
Fever
Headaches
Nausea or vomiting

Serious side effects:

Mood changes
Anaphylaxis

Question 16

What are asthma differentials?

Answer 16

Differentials:

Infection induced asthma
Exercise induced asthma
Atopic (allergen-induced) asthma
NSAID induced asthma

Question 17

What are the 2 stages of an asthma attack?

Answer 17

Early: Brochospasm
Late: Inflammation

Question 18

Consider the NICE guidelines for the treatment of asthma in the under 5’s

What drug would you choose as your first treatment for an under 5yr old and what is the mechanism of action for this medication?



Answer 18

SABA - short acting beta agonist e.g. Salbutamol

Targets beta-2 adrenergic receptors
Located on the bronchiole smooth muscle cells
Acts as an agonist
Reduces Ca2+ entry and prevents smooth muscle contraction
Prevents bronchoconstriction = opens up the airways to reduce bronchospasm

Question 19

SABA vs LAMA?

Answer 19

SABA = short acting beta agonist

LAMA = long acting muscarinic antagonist = causes bronchodilation

Question 20

What is a nebuliser?

What is an inhaler?

And what is a spacer?

Answer 20

Nebuliser = transforms liquid medication into a mist, that is inhaled and allows the drug to directly hit the target site, automatic medication release

Inhaler = dried powder format rather than mist

Spacer = holds the medicine in place so you can breathe it in easier, allows for medicine delivery to be more effective. Lower percentage of the drug entering the mouth at once, so less medication is lost through exhalation

Question 21

What are the 2 methods of administration of Salbutamol, and why do you think the inhalation route is preferred over the oral route?

Answer 21

Topical (inhalation) = via mouth into the lungs

Oral = ingestion, via mouth into the stomach

Inhalation = preferred due to direct delivery to the lungs and faster action, rather than oral, which takes a long time to travel through the system and may be broken down by the liver

Question 22

Why is a nebuliser the best method for delivering Salbutamol in an emergency situation?

Answer 22

Nebuliser - delivers medication as a mist, automatically

Requires less co-ordination than inhalers

Therefore a patient who may not be able to use an inhaler, the nebuliser = delivered to patients of all ages, and only requires normal breathing pattern

Question 23

What are the advantages of a nebuliser?

Answer 23

Many drug solutions
Can deliver combinations
Minimal patient cooperation required
Can deliver to patient of all ages

Question 24

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)

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

Answer 24

Some of the salbutamol goes down the oesophagus instead of the trachea

Poor inhaler technique / use

Some of the salbutamol absorbed by the mucus membranes in the oral cavity into systemic circulation

Exhalation of some of the salbutamol

Muco-ciliary clearance = salbutamol that enters the lungs is removed

Salbutamol absorbed within the systemic circulation of the lungs

Question 25

What do NSAIDs do in asthma?

What can be used as treatment for NSAID induced asthma?

Answer 25

NSAID induced asthma = overactivation of leukotrienes

NSAIDs block cyclooxygenase activity, leads to build up of arachidonic acid, which increases leukotriene production, which causes increased bronchoconstriction

Treatment- Montelukast:
Targets and blocks the leukotrienes, C4, D4, E4
On phospholipid membranes
Causes reduced bronchoconstriction

Question 26

What is the half life of salbutamol?

Answer 26

It’s half life is 2.5 - 5hrs

Question 27

Describe the selectivity of beta-2 agonists

Answer 27

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

Question 28

What is something we need to be aware of on administration of salbutamol?

Answer 28

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

Question 29

How do Fluticasone and Mometasone compare to cortisol?

Answer 29

Greater affinity for the glucocorticoid receptor compared to cortisol.

Question 30

What is the bioavailability of fluticasone and Mometasone?

Answer 30

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

Question 31

What is the bioavailability of budesonide?

Answer 31

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

Question 32

How does budesonide compare to fluticasone and mometasone?

Answer 32

Less potent than fluticasone and mometasone

Question 33

How should montelukast be taken for prophylaxis of exercise?

Answer 33

For induced bronchoconstriction (caused by exercise), montelukast should be administered at least 2 hours before initiating exercise.