Asthma Pharmacology

Question 1

What are the drugs for asthma?

Answer 1

salbutamol
fluticasone
mometasone
budesonide
montelukast

Question 2

What is the drug target for salbutamol?

Answer 2

Beta 2 (β2) adrenergic receptor

Question 3

What is the mechanism of action for salbutamol?

Answer 3

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

it is a bronchodilator

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 half life of salbutamol?

Answer 5

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

Question 6

Is the beta 2 selectivity of salbutamol absolute?

Answer 6

Beta 2 selectivity is not absolute – as a result, cardiac (beta 1) effects can be seen.
Hypokalaemia can be caused via an effect on sodium/ potassium ATPase. This effect can be exacerbated by coadministration with corticosteroids

(B1 is for the heart, one heart, b2 is for the lungs, 2 lungs (pneumonic to remember))

Question 7

What is the drug receptor of fluticasone?

Answer 7

Glucocorticoid receptor

Question 8

What is the mechanism of action for fluticasone?

Answer 8

Very powerful drugs. 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 9

What are the systemic and local side effects of fluticasone?

Answer 9

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
(Many others)

Question 10

What has a greater affinity for the glucocorticoid receptor, cortisol or fluticasone?

Answer 10

fluticasone

Question 11

What is the predominant systemic delivery of fluticasone and why?

Answer 11

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

Question 12

What is the drug target for mometasone?

Answer 12

Glucocorticoid receptor

Question 13

What is the mechanism of action for mometasone?

Answer 13

Very powerful drugs. Multiple actions on many different cell types. Mometasone 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 14

What are the side effects of mometasone?

Answer 14

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
(Many others)

Question 15

What has a grater affinity for the glucocorticoid receptor, mometasone or cortisol? And what is the systemic delivery route for mometasone and why?

Answer 15

mometasone

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

Question 16

What is the drug target for budesonide?

Answer 16

Glucocorticoid receptor

Question 17

What is the mechanism of action for budesonide?

Answer 17

Very powerful drugs. Multiple actions on many different cell types. Budesonide 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 18

Why is it ok that budesonide is inhaled?

Answer 18

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

Question 19

What is more potent, budesonide or mometasone?

Answer 19

budesonide is less potent than mometasone and fluticasone

Question 20

What is the drug target for montelukast?

Answer 20

CysLT1 leukotriene receptor

Question 21

What is the mechanism of action for montelukast?

Answer 21

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

Question 22

What are the side effects of montekulast?

Answer 22

Mild side effects:
Diarrhoea
Fever
Headaches
Nausea or vomiting

Serious side effects:
Mood changes
Anaphylaxis

Question 23

When should montelukast be administered, before, after or during exercise?

Answer 23

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

Question 24

What symptom gives asthma away?

Answer 24

wheeze gives it away (suggests airways are contracting, causing turbulent breathing)(wheezing also due to hypersensitivity e.g., if allergy, it’s either responding to the wrong thing or responding too much)
asthma

Question 25

What questions wouy=ld you ask someone who brought their child with asthma symptoms?

Answer 25

Is there a family history of asthma?
How often do symptoms occur?
Does coughing wake your child at night?
Do the symptoms accompany a cold or are they unrelated to colds?
How long do they last?
Has your child needed emergency care for breathing difficulties?
Does your child have any known pollen, dust, pet or food allergies?
Is your child exposed to cigarette smoke or other airborne irritants?

Question 26

What is the therapeutic objective for this patient?

Answer 26

Short term = Relief Relieve symptoms of breathlessness and expiratory wheeze during the acute asthma attack

Long term = Prevention Dampen/prevent the late phase of the asthma attack
Reduce the risk of further asthma attacks. Attempt to improve lung function

KEY POINT:
The management of asthma in children under 5 requires careful and relatively frequent monitoring. You can help minimize asthma symptoms by following a written asthma action plan you develop with the child’s doctor to monitor symptoms and adjust treatment as necessary.

Question 27

What is the difference and similarity between normal/ asthmatic/ medicated airways?

Answer 27

Question 28

How can you give salbutamol to a patient in a hospital setting?

Answer 28

oxygen-driven nebuliser

Question 29

What is the difference between oral and inhalation of aerosol salbutamol?

Answer 29

local vs systemic

oral is a much higher dose

Question 30

Answer 30

Question 31

Answer 31

exhaled
mucociliary clearance
absorption from lungs
oral swallowed
some will be absorbed across the mucous membrane in the oral cavity and pharynx

Question 32

What can you use to increase the function of the inhaler?

Answer 32

spacer

Question 33

What is the vicious cycle of viral infection and asthma?

Answer 33

Common viral infections (e.g. rhinovirus) are known to release mediators that specifically activate eosinophils. Eosiniophils can induce epithelial damage (e.g. due to release of major basic protein). This increases susceptibility to viral infections. Vicious cycle

Question 34

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 34

first pass inactivation

Question 35

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 35