Bronchodilators: Phosphodiesterase inhibitors (xanthine derivatives)

Question 1

Gas GPCR are present on all B-adrenergic receptors. Organise the following intracellular pathway that occurs when these receptors become active?

1 - pKA moves around cell and phosphorylates target proteins triggering a cellular response
2 - adenylyl cyclase (AC) becomes active
3 - cAMP binds and activates protein kinase A (pKa)
4 - AC takes 2 phosphates from ATP and becomes cyclic adenosine monophosphate (cAMP)

Answer 1

2 - adenylyl cyclase (AC) becomes active
4 - AC takes 2 phosphates from ATP and becomes cyclic adenosine monophosphate (cAMP)
3 - cAMP binds and activates protein kinase A (pKa)
1 - pKA moves around cell and phosphorylates target proteins triggering a cellular response

Question 2

B agonists used for respiratory conditions such as asthma and COPD are able to activate the Gas GPCR intracellular pathway and induce smooth muscle vasodilation. However, to ensure the level of cAMP does not become excessive, which enzyme is responsible for inhibiting cAMP activation?

1 - phosphodiesterase (PDE)
2 - HMG-CoA reducatase
3 - adenylyl cylcase
4 - phospholipase C

Answer 2

1 - phosphodiesterase (PDE)

• converts the active cAMP into the inactive form 4-AMP

Question 3

Theophylline is a medication given orally to COPD patients or patients with chronic asthma. What is the mechanisms of action of this drug?

1 - inhibits phosphodiesterase
2 - inhibits GPCR Gaq
3 - antagonist of M3
4 - inhibits IgE

Answer 3

1 - inhibits phosphodiesterase
- increases cAMP

• also inhibits adenosine, which causes vasoconstriction in the smooth muscle of the lungs

Question 4

Theophylline is a medication given orally to COPD patients or patients with chronic asthma. It is able to inhibit phosphodiesterase, which increases cAMP levels in smooth muscles and thus vasodilation. What effects does this drug have on the lungs?

1 - bronchodilation
2 - reduced mucus production
3 - increased mucus removal
4 - reduced IgE

Answer 4

1 - bronchodilation

Question 5

Theophylline is a medication given orally to COPD patients or patients with chronic asthma. It is able to inhibit phosphodiesterase, acting as a bronchodilator. This drug has a narrow therapeutic window so needs to be monitored. What important enzyme metabolises this drug?

1 - cytochrome P450
2 - LFT
3 - GGT
4 - AST

Answer 5

1 - 1 - cytochrome P450

• if other drugs are inducers or inhibitor of cytochrome P450 then their affects could be altered

Question 6

In chronic asthma and COPD, are these medications ever given in isolation?

Answer 6

• no