12 - Asthma Drugs

Question 1

Outline the pathology of asthma (3)…

Answer 1

• Bronchoconstriction
• Mucus hypersecretion
• Airway inflammation

Question 2

The disease process of asthma comprises of 2 phases…

Answer 2

The immediate phase (bronchoconstriction) and the delayed phase (inflammation)

Question 3

In the immediate phase, allergen stimulates ______ cells, which release histamine and ____________ . This leads to __________, and eventually inflammation as part of the ______ phase.

Answer 3

In the immediate phase, allergen stimulates mast cells, which release histamine and leukotrienes. This leads to bronchospasm, and eventually inflammation as part of the delayed phase.

Question 4

The immediate phase of asthma is characterised by the release of histamine and leukotrienes. Which leukotrienes are involved in triggering bronchospasm versus inflammation…

Answer 4

• Bronchospasm
  
  • LTC₄, LTD₄
• Inflammation
  
  • LTB₄, LTC₄, LTD₄

Question 5

The delayed phase of asthma is characterised by…

Answer 5

• Vasodilation, odemea and mucus secretion
• An influx of cytokine-releasing lymphocytes
  
  • Damage to epithelium and bronchi
  • Immune response
  • ∴ hypersensitivity

Question 6

Drugs used to treat asthma and the part of the disease process they target…

Answer 6

• Chromolyn - Mast cells
• β2 agonists, M agonists, xanthines - Bronchospasm
• CysLT1 agonist - Leukotriene release
• Glucocorticoids - Inflammation (delayed phase)

Question 7

β2 agonists target which aspect of asthma?

Answer 7

Bronchospasm

Question 8

Describe how β2 agonists may relieve symptoms of asthma…

Answer 8

• Mimics adrenaline (promotes bronchodilation as cAMP activation leads to smooth muscle relaxation in the bronchi)
• May inhibit mast cell activation

Question 9

β2 agonists are given by inhalation and can be both ______ or ______ acting. Side effects include _______ and ______.

Answer 9

β2 agonists are given by inhalation and can be both long or short acting. Side effects include tolerance and tremor.

Question 10

Give 2 examples of β2 agonists used to treat asthma…

Answer 10

• Salbutamol
• Salmeterol (ꜛT_1/2)

Question 11

M (muscarinic) antagonists such as ________ block ___-mediated bronchoconstriction

Answer 11

M (muscarinic) antagonists such as ipratropium block M₃-mediated bronchoconstriction

Question 12

With reference to the sympathetic and parasympathetic divisions of the autonomic nervous system, state the difference between the action of salbutamol and ipratropium.

Answer 12

They both achieve bronchodilation…

• Salbutamol as a sympathetic (B2) agonist ↑
• Ipratropium as a parasympathetic (mAch) antagonist ↓

Question 13

Xanthines target:

a) delayed phase
b) immediate phase
c) both phases

Answer 13

Xanthines target:

a) delayed phase
b) immediate phase

c) both phases

They may block phosphodiesterase, ↓cAMP leading to bronchodilation (immediate phase). They also have anti-inflammatory properties (delayed phase).

Question 14

Give an example of a Xanthine

Answer 14

Theophylline

Question 15

Describe the main disavantage of Xanthines (such as theophylline)…

Answer 15

Narrow theraputic window (so not used much anymore)

Question 16

Glucocorticoids, sodium cromolyn and CysLT1 agonists all target the ( immediate / delayed ) phase…

Answer 16

Glucocorticoids, sodium cromolyn and CysLT1 agonists all target the immediate phase.

Question 17

Outline how glucocorticoids suppress inflammation…

Answer 17

• ↑ lipocortin
  
  • Inhibits phospholipase A₂
    
    • ↓ inflammatory mediators

Question 18

Glucocortiocoids are effective at reducing inflammation. However, they carry significant side effects, such as…

Answer 18

Immunosuppresion, which can lead to oral candidiasis.

(administration via inhalation minimises risk of systemic side effects)

Question 19

Sodium Cromolyn was proposed to work as a mast cell stabiliser. In reality they also inhibit…

Answer 19

Hyper-responsivity

Question 20

Cysteinyl-leukotriene receptor (CyLT1) antagonists target…

a) immediate phase
b) delayed phase
c) both phases

Answer 20

Cysteinyl-leukotriene receptor (CyLT1) antagonists target…

a) immediate phase
b) delayed phase

c) both phases

Question 21

Cysteinyl-leukotriene receptor (CyLT1) antagonists are used in cases of _____ asthma. They are ( more / less ) effective than glucocorticoids at treating the delayed phase.

Answer 21

Cysteinyl-leukotriene receptor (CyLT1) antagonists are used in cases of mild asthma. They are less effective than glucocorticoids at treating the delayed phase.

Question 22

Coughing is a reflex action to expel foreign bodies, however in some cases it may be distressing or exhausting.

Cough is regulated by sensory receptors which send signals to a ‘cough centre’ in the ___________ . Efferent pathways innervate _________ and _______ nerves which regulate respiratory muscle.

Answer 22

Coughing is a reflex action to expel foreign bodies, however in some cases it may be distressing or exhausting.

Cough is regulated by sensory receptors which send signals to a ‘cough centre’ in the hypothalamus. Efferent pathways innervate intercostal and phrenic nerves which regulate respiratory muscle.

Question 23

List drugs used to treat cough…

Answer 23

• Reduce receptor sensitivity
  
  • Menthol vapour
  • Eucalyptus oil
  • Benzocaine (topical local anaesthetic)
• Targeting the cough centre
  
  • Opiod receptor agonists (such as codeine or dextromethorphan)

Question 24

Name 3 drugs which may have adverse effects on respiratory disease (such as asthma)…

Answer 24

• β-adrenoreceptor agonists (such as propanalol) can trigger severe, fatal asthma
• ACE inhibitors (such as captopril) can induce cough
• NSAIDS (such as aspirin) may precipitate asthma