Leukotriene Receptor Antagonists

Question 1

What are leukotrienes?

1 - immune cells in the lungs
2 - proteins produced by epithelial cells in the lungs
3 - anti-inflammatory molecules
4 - inflammatory molecules

Answer 1

4 - inflammatory molecules

• eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA)

Question 2

Leukotrienes are inflammatory molecules that are eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA). Which 2 of the following are the MAIN producers of these cells?

1 - mast cells
2 - eosinophils
3 - T helper cells
4 - macrophages

Answer 2

1 - mast cells
2 - eosinophils

Question 3

Once releases leukotrienes activate cells by binding with what?

1 - GPCR
2 - tyrosine kinase receptors
3 - cytoplasm receptors
4 - through Na+ co-transporter

Answer 3

1 - GPCR
- specifically CysLT1 GPCRs
- once bound they initiate inflammation and bronchoconstriction of the smooth muscle in the lungs

Question 4

What is the main Leukotriene Receptor Antagonists (LTRA) that wee need to be aware of?

1 - salbutamol
2 - montelukast
3 - formoterol
4 - theophylline

Answer 4

2 - montelukast
- inhibits leukotrienes ability to bind with CysLT1 GPCRs

• administered orally at 10mg

Question 5

Leukotrienes are produced from arachidonic acid by the enzyme 5-lipoxygenase. The leukotrienes are then able to bind with leukotriene receptors on the bronchial smooth muscle and mucus cells. What are the effects following this?

1 - reduced mucus production and vasodilation
2 - increased mucus production and vasodilation
3 - increased mucus production and vasoconstriction
4 - increased mucus production

Answer 5

3 - increased mucus production and vasoconstriction

• also increase vascular permeability, increasing the number of immune cells

Question 6

Leukotrienes are produced from arachidonic acid by the enzyme 5-lipoxygenase. The leukotrienes are then able to bind with leukotriene receptors on the bronchial smooth muscle and mucus cells. Montelukast is the core drug we need to be aware to inhibit Leukotrienes. What is the mechanisms of action of this drug?

1 - bind and inhibit mast cells
2 - bind leukotrienes receptors on smooth muscle
3 - reduce vascular permeability
4 - inhibit IgE production

Answer 6

2 - bind leukotrienes receptors on smooth muscle

• reduce vascular permeability
• reduce inflammation
• induce bronchodilation

Question 7

What are the indications for Montelukast?

1 - exercise induced asthma, COPD, cold air and aspirins
2 - exercise induced asthma, allergens, cold air and aspirins
3 - COPD, allergens, cold air and aspirins
4 - exercise induced asthma, allergens, chronic asthma

Answer 7

2 - exercise induced asthma, allergens, cold air and aspirins

Question 8

Montelukast is generally well tolerated, but does have some side effects. Which of the following is an adverse event, BUT NOT a common one?

1 - headaches
2 - GI upset
3 - neuropsychiatric reactions
4 - abdominal pain

Answer 8

3 - neuropsychiatric reactions

• can include sleep disturbance, depression and agitation

Question 9

Montelukast is generally well tolerated, but does have some side effects. These can increase the risk of what?

1 - upper airway infections
2 - lower airway infections
3 - mucous plugs
4 - rhinitis

Answer 9

1 - upper airway infections

Question 10

Montelukast is metabolised by cytochrome P450 enzymes. What would an inhibitor and induce of CYP 450 have on Montelukast?

Answer 10

• inducer = reduced efficacy as it would be metabolised quickly
• inhibitor = increased plasma levels and potentially increased risk of adverse events