L3 - Drugs Influencing Airway Resistance

Question 1

What is the equation for resistance?

Answer 1

R α 1/r^4

Question 2

Where in the respiratory tract is resistance the greatest?

Answer 2

In the large and medium sized bronchi.

Question 3

What types of innervation does the smooth muscle in the airways have?

Answer 3

NANC innervation (non andronergic non cholinergic innervation).

Parasympathetic innervation/

Question 4

What is the effect of stimulation of NANC innervation of the smooth muscle in the airways?

Answer 4

• Bronchodilation.

- But in asthma substance P may cause bronchoconstriction.

Question 5

What is the effect of stimulation of parasympathetic innervation of the smooth muscle in the airways?

Answer 5

Bronchoconstriction.

Question 6

What receptors are stimulated in the parasympathetic innervation of the smooth muscle in the airways?

Answer 6

M3 receptors.

Question 7

What are the transmitters of NANC innervation?

Answer 7

Nitric oxide (NO) and vasoactive intestinal peptide (VIP).

Question 8

Where are β2 receptors found?

Which ligand binds to β2 receptors?

What is the effect of activation of β2 receptors?

Answer 8

• β2 receptors are found on airway smooth muscle.
• Circulating adrenaline binds to β2 receptors.
• β2 receptors cause:
• Bronchodilation,
• Inhibition of mast cell activity,
• Promotion of muco-ciliary escalator activity.

Question 9

What is degranulation?

Where does it occur?

Answer 9

• A cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles known as granules.
• Occurs in granulocytes and mast cells.

Question 10

How do mast cells contribute to asthma pathology?

Answer 10

• Mediators released by degranulation of mast cells cause bronchoconstriction.
• e.g. Histamine, platelet activating factor and leukotrienes.

Question 11

What effect does CO2 have on the diameter of the airways? Why is this useful?

Answer 11

• CO2 causes bronchodilation.

- Important for ventilation-perfusion matching.

Question 12

How does parenchyma help lower airway resistance?

Answer 12

• Airways are embedded in lung parenchyma.
• Parenchyma provides ‘radial traction’ to keep the airways open.
• Inflation increases radial traction and reduces airway resistance.
• Parenchyma also ensures alveolar interdependence.

Question 13

How is airway resistance increased in COPD?

Answer 13

Loss of both radial traction and alveolar interdependence.

Question 14

List 3 signs and symptoms of asthma.

Answer 14

1 - Episodes of bronchoconstriction.

2 - Bronchial hypersensitivity - airway mucosa inflammation.

3 - Increased airway secretions.

Question 15

What is ipratropium?

Answer 15

• An inhaled muscarinic antagonist that is an analogue of atropine.
• Blocks the bronchoconstricting action of ACh.

Question 16

How do β2 agonists cause bronchodilation?

Answer 16

• Bind to β2 receptors.
• β2 receptors are G proteins with a Gs alpha subunit, so stimulate the AC / cAMP / PKA pathway.
• Intracellular Ca2+ decreases, increasing bronchodilation and reducing inflammation.

Question 17

List 2 β2 agonists.

Answer 17

1 - Salbutamol (short acting).

2 - Salmeterol (long acting).

Question 18

What is a PDE inhibitor?

Answer 18

• An inhibitor of phosphodiesterase.
• Inhibition causes increase in cAMP pathways.
• Increase in cAMP pathway increases bronchodilation and reduce inflammation.

Question 19

What are methylxanthines?

Give an example of a methylxanthine.

List 4 side effects of theophylline.

Answer 19

• PDE inhibitors.
• e.g. Theophylline.

- Side effects include:
1 - Headaches.
2 - Restlessness.
3 - Abdominal symptoms.
4 - Arrhythmias.

Question 20

List 3 side effects of β2 agonists.

Answer 20

1 - Tachycardia.

2 - Tremor.

3 - Airway hyper-responsiveness.

Question 21

What is omalizumab and how does it work?

Answer 21

• A monoclonal anti-IgE antibody.
• Reduces circulating IgE, reducing mast cell degranulation and inflammation.
• Used in severe allergic asthma.

Question 22

List 3 symptoms of aspirin-induced asthma.

Answer 22

1 - Rhinorrhea.

2 - Nasal congestion.

3 - Sinusitis.

Question 23

What is a biochemical difference in patients that are aspirin intolerant to those that are not?

Answer 23

• Aspirin intolerant patients upregulate 5-lipoxygenase in response to taking aspirin.
• 5-lipoxygenase is involved in the leukotriene pathway.

Question 24

What are H1 receptors?

Answer 24

A histamine receptor that plays a role in inflammation.

Question 25

What is ketotifen and how does it work?

Answer 25

• A H1 receptor antagonist.
• Acts as an anti-inflammatory after 6-12 weeks treatment.
• Reduces reliance on steroids.

Question 26

What is a prophylactic treatment?

Answer 26

A preventative treatment.

Question 27

What is sodium cromoglicate / cromolyn and how does it work?

Answer 27

• A prophylactic treatment.

- Inhibits the release of inflammatory mediators from mast cells.

Question 28

Name a side effect of ketotifen.

Answer 28

Drowsiness (10-15% patients).

Question 29

List 3 side effects of sodium cromoglicate / cromolyn.

Answer 29

1 - Coughing.

2 - Wheezing.

3 - Dry throat.

Question 30

What is zileuton and how does it work?

Answer 30

• A leukotriene formation antagonist.
• Targets the leukotriene pathway.
• Inhibits 5-lipoxygenase, halting the pathway.

Question 31

What are montelukast, pranlukast and zafirlukast? What do they do?

Answer 31

• Leukotriene receptor antagonists.
• Used in severe chronic and exercise-induced asthma.
• Causes bronchodilation, decreases mucus secretion and reduces inflammation.

Question 32

What is the result of leukotrienes binding to leukotriene receptors (CysLT1 receptors)?

Answer 32

Bronchoconstriction.

Question 33

What initiates the leukotriene pathway?

Answer 33

The leukotriene pathway is an inflammatory response.

Question 34

How does atropine reduce airway resistance?

Answer 34

It antagonises the parasympathetic innervation to the smooth muscle (it is a muscarinic antagonist).

Question 35

How do β2 agonists cause inflammation?

Answer 35

• β2 receptors are found on inflammatory and immune cells.

- stimulation of these receptors decreases their activity.