Pharmacology of airway disease

Question 1

Use an acronym to describe which drugs should be administered in the event of a severe acute asthma attack.

Answer 1

O, SHIT

Oxygen
Salbutamol
Hydrocortisone
Ipratropium
Theophylline

Question 2

Describe the effect of the sympathetic nervous system on the lungs in terms of which mediator acts on which nerve fibres and what this causes.

Answer 2

Noradrenaline acts on B2-adrenergic receptors on bronchial smooth muscle which causes bronchodilation

Question 3

Describe the effect of the parasympathetic nervous system on the lungs in terms of which mediator acts on which nerve fibres and what this causes.

Answer 3

Acetylcholine acts on muscarinic (M3) receptors on bronchial smooth muscle which causes bronchoconstriction

Question 4

What 2 key effects does protein kinase A have which aid in bronchodilation?

Answer 4

Promotes dephosphorylation of myosin light chains

Reduces cytoplasmic calcium

Question 5

Describe in detail how the binding of salbutamol to a B2-adrenergic receptor leads to bronchodilation.

Answer 5

The binding of salbutamol to B2-adrenergic receptor activates a G-protein. The activated G-protein stimulates the enzyme adenylate cyclase, located in the cell membrane.

Adenylate cyclase converts ATP into cAMP.

cAMP activates protein kinase A.

Protein kinase A promotes the dephosphorylation of myosin light chains and reduces cytoplasmic calcium. Myosin and calcium are both required for muscle contraction, so the overall effect is bronchodilation

Question 6

Which enzyme inactivates cAMP?

Answer 6

Phosphodiesterase

Question 7

What is the MOA of methylxanthines?

Answer 7

Blockade of phosphodiesterase enzyme, which leads to increased levels of cAMP since phosphodiesterase breaks down cAMP

Question 8

In what form are methylxanthines given?

Answer 8

Oral tablet (or IV in an acute asthma attack)

Question 9

How does acetylcholine binding to M3 muscarinic receptors cause bronchoconstriction?

Answer 9

The binding of acetylcholine to M3 muscarinic receptor activates a G-protein. The activated G-protein stimulates the enzyme phospholipase C, which brings about the production of Inositol triphosphate (IP3). IP3 stimulates the release of calcium, which promotes muscle contraction

Question 10

What is the MOA of antimuscarinics?

Answer 10

Blockade of M3 muscarinic receptors to prevent binding of acetylcholine

Question 11

Which specific leukotriene receptors does montelukast block?

Answer 11

CysLT1

Question 12

Which receptor do corticosteroids bind to? What is the location of this receptor?

Answer 12

Glucocorticoid receptor

Intracellular

Question 13

List 2 anti-inflammatory mediators which corticosteroids enhance.

Answer 13

Lipocortin-1

Secretory leukocyte peptidase inhibitor (SLPI)

Question 14

List 6 key side effects of corticosteroids.

Answer 14

Moon face
Easy bruising
Osteoporosis
Hyperglycaemia
Poor wound healing
Increased susceptibility to infection

Question 15

What are the 2 b2-adrenergic agonists?

Answer 15

Salbutamol (short-acting)
Salmeterol (long-acting)

Question 16

What are the 2 key side effects of b2-adrenergic agonists?

Answer 16

Tachycardia
Tremor

Question 17

What are the 3 antimuscarinics?

Answer 17

Ipratropium (short-acting)
Tiotropium (long-acting)
Glycopyrronium (long-acting)

Question 18

What is the key side effects of antimuscarinics?

Answer 18

Dry mouth

Question 19

What are the 2 methylxanthines?

Answer 19

Theophylline
Aminophylline

Question 20

What are the 2 key side effects of methylxanthines?

Answer 20

Cardiac arrhythmia
Seizures

Question 21

What are the 3 corticosteroids?

Answer 21

Beclometasone (inhaled)
Prednisolone (oral)
Hydrocortisone (IV)

Question 22

What are the 2 leukotriene receptor antagonists?

Answer 22

Montelukast
Zafirlukast

Question 23

What are the 2 key side effects of leukotriene receptor antagonists?

Answer 23

Abdominal pain
Headache