PHARM Asthma & COPD - Week 2

Question 1

Asthma pathology

Answer 1

Increased smooth muscle, build up of mucous, BM thickening.

Question 2

Symptoms of asthma

Answer 2

• Recurring episodes of breathing problems.
• Shortness of breath.
• Wheezing/chest tightness
• Night-time or early morning coughing.

Question 3

2 x types of asthma

Answer 3

• Extrinsic – allergic/T2 type (most common)
  o Involves IgE antibodies/mast cell & basophilic degranulation
  o Triggered by re-exposure to allergens (e.g., pollen, house dust mites, pets).
• Intrinsic – non-allergic/non-specific (more severe)
  o Hyper-responsive airways
  o ‘Non-specific bronchial hyperreactivity’
  o Triggered by exercise, cold, infection.

Question 4

What immune cells are responsible for driving 2 types of asthma?

Answer 4

T2/allergic/extrinsic asthma - high eosinophils
Non-T2/non-allergic/non-specific/intrinsic asthma - high neutrophils

Question 5

SABA expand. Drug type examples.

Answer 5

Short acting B2 agonist. Salbutamol/albuterol (ventolin/asmol).

Question 6

SABA administration.

Answer 6

Inhalation.

Question 7

What do SABAs protect against?

Answer 7

Exercise-induced asthma.

Question 8

MOA SABAs

Answer 8

• MOA: mimick effect of adrenaline with selective action on B2 adrenoreceptors -> adenylcyclase -> c35AMP -> muscle relaxation/bronchodilation

Question 9

SABA onset

Answer 9

5-15min

Question 10

SABA duration of action

Answer 10

3-6hrs

Question 11

SABA adverse effects

Answer 11

• Adverse effects: tachycardia, muscle tremor, receptor downreglation/desensitisation decreases efficacy in cases of overuse, infection, smoking, underlying inflammation left untreated.

Question 12

LABA expand. Drug examples.

Answer 12

Long acting B2 adrenoreceptor agonist. Formoterol.

Question 13

LABA administration.

Answer 13

Inhalation.

Question 14

What do LABA & ICS protect against?

Answer 14

T2-type asthma (w eosinophilic response)

Question 15

When should LABA & ICS be used?

Answer 15

Short term exacerbation OR for severe asthma unresponsive to other therapies.

Question 16

LABA & ICS MOA

Answer 16

• MOA : steroids must enter cytoplasm of target cells -> acts on receptor -> translocates to nucleus -> regulating gene expression -> promote anti-inflammatory protein synthesis -> bind to pro-inflammatory transcription factors (e.g., NFkB) to downregulate inflammatory factors

Question 17

LABA & ICS adverse effects

Answer 17

• Adverse effects: suppress endogenous glucocorticoid synthesis, Cushing’s syndrome, suppress infection & injury response, behavioural disturbances, cataracts, glaucoma, metabolic effects, growth suppression, poor delivery can cause dysphonia & oral thrush.

Question 18

Omalizumab target. Recommended for which group of pts.

Answer 18

• Omalizumab – recombinant mAb against IgE (use restricted to severe, persistent allergic asthma uncontrolled even with high doses of corticosteroids).

Question 19

Mepolizumab target. Recommended for which group of pts.

Answer 19

• Mepolizumab – recombinant mAb against IL-5 (use restricted to severe eosinophilic asthma in adults only).

Question 20

Dupilumab target. Recommended for which group of pts.

Answer 20

• Dupilumab – recombinant mAb against IL-4/IL-3 receptor (use restricted to adults with severe allergic asthma).

Question 21

Symptoms of COPD

Answer 21

• Shortness of breath
• Wheezing
• Coughing
• Increased mucous production
• Recurrent chest infections
• Muscle wasting.

Question 22

Potential causes of COPD

Answer 22

• Smoking
• Frequent lung infections as a child
• Indoor smoke (e.g., wood, coal, cow dungs, crop residues)
• Occupational dust @ chemical exposure
• Genetic reasons (a-1 antitrypsin deficiency)

Question 23

What can a1 antitrypsin deficiency lead to? How?

Answer 23

Early onset emphysema. Lungs lack a1 antitrypsin coating - leaving them open to damage by neutrophil elastase. Liver damage also occurs due to trapped a1 antitrypsin present here.

Question 24

Signs & symptoms of chronic bronchitis.

Answer 24

Remember blue bloater & pink puffer.
Overweight, cyanosis, elevated Hb, peripheral oedema, wheezing, chronic daily productive cough.

Question 25

Signs & symptoms of emphysema.

Answer 25

Remember blue bloater & pink puffer.
Older & thinner, severe dyspnoea, quiet chest, CXRT revealing hyperinflation w flattened diaphragms & permanent enlargement & destruction of airspaces distal to the terminal bronchiole.

Question 26

What immune cells are responsible for driving COPD?

Answer 26

Neutrophils.

Question 27

SAMA expand. Drug examples.

Answer 27

Short acting M3 antagonist. Ipatropium/tiotropium.

Question 28

SAMA adverse effects.

Answer 28

• Adverse effects: inhibit salivation -> dry mouth, blurred vision, urinary retention.

Question 29

SAMA effect.

Answer 29

• Protect against increased parasympathetic drive by decreasing airway muscle contraction & mucous production.

Question 30

When are ICS used to treat pts w COPD?

Answer 30

In pts who have eosinophilic elevation.

Question 31

When are short term oral steroids usually used in pts w COPD?

Answer 31

Recovery from COPD exacerbations.

Question 32

Issues with steroid use in pts w COPD?

Answer 32

Suppressed immunes system -> increased risk of pneumonia.

Question 33

Therapy for pts w a1-antitrypsin deficiency

Answer 33

Replacement therapy (derived from human plasma).

Question 34

Step wise treatment for asthma. Examples of common medications prescribed.

Answer 34

ICS-LABA/ICS-SABA as needed, regular, low-dose ICS-LABA/ICS-SABA, medium-dose, regular ICS-LABA, add LAMA (consider high-dose, regular ICS-LABA OR anti-IgE, anti-IL5…).
LABA e.g., formoterol/symbicort.
ICS e.g., budesonide.
SABA e.g., salbutamol/ventolin.

Question 35

Step wise treatment for COPD.

Answer 35

SABA or SAMA as needed, SABA or SAMA w LABA or LAMA, previous w ICS, LABA & LAMA & ICS recently approved, previous (consider anti-inflammatory agents).

Question 36

What drug classes are typically considered relievers? Preventers?

Answer 36

SABA/SAMA. LABA/LAMA/ICS.

Question 37

Why are SABAs preferred over SAMAs for asthma treatment?

Answer 37

SABAs preferred for asthma compared to SAMAs - as SABAs target all leukotrienes, histamines… whereas SAMAs only target ACh mediator.