Pharmacology of Asthma

Question 1

What is the primary mechanism of action of Salbutamol?

Answer 1

Agonist at the Beta 2 receptor on airway smooth muscle cells. Activation reduces Ca2+ entry, preventing smooth muscle contraction.

Question 2

What is the drug target of Salbutamol?

Answer 2

Beta 2 adrenergic receptor

Question 3

What are the main side effects of Salbutamol?

Answer 3

• palpitations
• agitation
• tachycardia
• arrhythmias
• hypokalaemia (at higher doses)

Question 4

What is the main classification of salbutamol?

Answer 4

• SABA (short acting beta agonist)

- half life of 2.5-5 hours

Question 5

How selective is salbutamol?

Answer 5

• not absolute
• cardiac (beta 1) effects can be seen
• hypokalaemia caused by an effect on. Na/KATPase
  (effect worsened with corticosteroids)

Question 6

What is the primary mechanism of action of Fluticasone?

Answer 6

• powerful
• multiple actions, on different cell types
• directly decreases inflammatory cells (eosinophils, monocytes, mast cells, macrophages and dendritic cells) and the cytokines that they produce.
  (inhibits IL5)

Question 7

What is the primary drug target of Fluticasone?

Answer 7

Glucocorticoid receptor (in eosinophils)

Question 8

What are the local side effects of Fluticasone?

Answer 8

• sore throat
• hoarse voice
• opportunistic oral infections

Question 9

What are the systemic side effects of Fluticasone?

Answer 9

• growth retardation in children
• hyperglycaemia
• decreased bone mineral density
• Immunosuppression
• effect on mood

Question 10

Why is Fluticasone effective?

Answer 10

Has a higher affinity for the glucocorticoid receptor in comparison to cortisol

Question 11

What is the mode of delivery of Fluticasone?

Answer 11

oral bioavailability <1%

systemic delivery via the inhaled route is through pulmonary vasculature

Question 12

What is the primary mechanism of Mometasone?

Answer 12

• powerful
• multiple actions on different cell types
• directly decreases inflammatory cells (eosinophils, monocytes, mast cells, macrophages, and dendritic cells) and the cytokines they produce.

Question 13

What is the primary target of Mometasone?

Answer 13

Glucocorticoid receptor

Question 14

What are the local side effects of Mometasone?

Answer 14

• sore throat
• hoarse voice
• opportunistic oral infections

Question 15

What are the systemic side effects of Mometasone?

Answer 15

• growth retardation in children
• hyperglycaemia
• decreased bone mineral density
• immunosuppression
• effects on mood

Question 16

Why is Mometasone effective?

Answer 16

greater affinity for the glucocorticoid receptor in comparison of cortisol.

Question 17

What is the mode of delivery of Mometasone?

Answer 17

oral bioavailability of <1%, due to excretion be the liver (therefore not a LT option, and WILL cause liver damage)
systemic delivery via inhalation is through pulmonary vasculature

Question 18

What is the primary mechanism of action of Budesonide?

Answer 18

• powerful
• multiple actions on different cell types
• directly decreases inflammatory cells
  (eosinophils, monocytes, macrophages and dendritic cells) and the cytokines they produce.

Question 19

What is the primary drug target of Budesonide?

Answer 19

Glucocorticoid receptor

Question 20

What are the local side effects of Budesonide?

Answer 20

• hoarse voice

- opportunistic oral infections

Question 21

What are the systemic side effects of Budesonide?

Answer 21

• growth retardation in children
• hyperglycaemia
• decreased bone mineral density
• immunosuppression
• effects on mood

Question 22

How effective is Budesonide?

Answer 22

less potent than Fluticasone and Mometasone

Question 23

What is the mode of delivery of Budesonide?

Answer 23

oral bioavailability <10%

inhaled Budesonide results in systemic absorption through the GI tract

Question 24

What is the primary mechanism of action of Montelukast?

Answer 24

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

Question 25

What is the primary drug target of Montelukast?

Answer 25

CysLT1 leukotriene receptor

Question 26

What are the mild side effects of Montelukast?

Answer 26

- diarrhoea - fever - headaches - nausea - vomiting

Question 27

What are the serious side effects of Montelukast?

Answer 27

- mood changes | - anaphylaxis

Question 28

When should Montelukast be administered to prevent exercise-induced bronchoconstriction?

Answer 28

at least 2 hours before initiating exercise

Question 29

When is an asthma case NOT considered urgent?

Answer 29

- no previous history of hospitalisation - normal physical examinations - not unconscious or drowsy - able to speak

Question 30

What is the short term therapeutic objective when treating an asthma?

Answer 30

Relief | - reduce symptoms of breathlessness and expiratory wheeze during an acute attack

Question 31

What is the long term therapeutic objective when treating an asthma?

Answer 31

Prevention - dampen/prevent the late phase of an attack - reduce the risk of further attacks - attempt to improve asthma attacks

Question 32

What is the first line treatment for children <5 with suspected asthma?

Answer 32

offer SABA, reliever therapy | - symptom relief and all maintenance therapy

Question 33

Why is inhalation the preferred administration route of Salbutamol?

Answer 33

- lower inhaled dose - direct delivery to tissues (instead of systemic) - fewer side effects

Question 34

What is the advantages of using inhalation to administrate drugs?

Answer 34

- minimal patient co-operation required - all ages - normal breathing pattern - concentration and dose can be modified - can deliver combinations of different drugs

Question 35

Why is only 20% of inhaled salbutamol actually impacting the lungs?

Answer 35

- poor inhalation technique - absorbed in the oesophagus, can cause a yeast infection due to inhaled steroids - absorbed in the blood and straight to the heart (quick access to the bloodstream)

Question 36

How do NSAIDs induce asthma?

Answer 36

prevents the conversion of arachidonic acid to prostaglandins (via cyclooxygenase) by inhibition cycloosygenase. Therefore increased luekotrines are produced leading to more inflammation and more bronchospasms.