PHRM 825: Asthma - Hazbun

Question 1

How are mast cells activated?

Answer 1

Cross linking of the Fc receptor and IgE via an antigen

Question 2

What do mast cells release?

Answer 2

PGD2, LTC4, LTD4, Histamine, tryptase

Question 3

What causes the early reaction in asthma?

Answer 3

Antigen binding to IgE antibodies triggering degranulation of mast cells

Question 4

What causes the delayed reaction in asthma?

Answer 4

Activation of TH2 lymphocytes

Question 5

What do eosinophils contain a lot of?

Answer 5

histamine molecules

Question 6

Which receptors cause the development of hyperplasia?

Answer 6

EGFR and CLCA

Question 7

Which receptor causes the maintenance of hyperplasia?

Answer 7

Bcl-2

Question 8

What polymorphism contributes to goblet cell hyperplasia?

Answer 8

R576 polymorphism in the IL-4alpha receptor

Question 9

What polymorphism induces hyperreactivity to inhaled antigens?

Answer 9

Q576R in the IL-4alpha receptor

Question 10

Which receptors are upregulated in asthma?

Answer 10

IL-13

Question 11

What happens to the epithelium during airway remodeling?

Answer 11

Mucous hyperplasia and hypersecretion

Question 12

What happens to the basement membrane during airway remodeling?

Answer 12

It thickens

Question 13

What happens to the smooth muscle during airway remodeling?

Answer 13

It undergoes hypertrophy (increase in size, NOT NUMBER of cells)

Question 14

What are 3 results of COPD?

Answer 14

• Fibrosis of small airways
• Alveolar wall destruction (aka emphysema)
• Mucus hypersecretion

Question 15

What are the main 3 places that the CFTR channel is expresses?

Answer 15

• Airway epithelium
• Sweat duct epithelium
• Pancreatic duct epithelium

Question 16

What is an early sign of CF and what causes it?

Answer 16

Excessively salty sweat - caused by loss of CFTR function

Question 17

What are the 2 treatment strategies in asthma?

Answer 17

• Bronchodilation

- Anti-inflammation

Question 18

What is a prevention strategy for asthma?

Answer 18

Inhibition of mast cell degranulation

Question 19

SABAs are resistant to what enzymes?

Answer 19

COMT

Question 20

LABAs are resistant to what enzymes?

Answer 20

COMT and MAO

Question 21

What is the administration route of choice for acute attacks?

Answer 21

Inhalation

Question 22

What is one advantage of using inhaled products versus oral products?

Answer 22

Fewer systemic adverse effects

Question 23

What medications are contraindicated as monotherapies in asthma but not COPD?

Answer 23

LABAs (e.g. salmeterol and formoterol)

Question 24

What do glucocorticoids do?

Answer 24

Decreases the hyperresponsiveness of bronchial smooth muscle cells that occurs in chronic asthma

Question 25

Which medication has a narrow therapeutic range?

Answer 25

Theophylline (10-15mcg/mL)

Question 26

Pre-treatment with Cromolyn sodium and Nedocromil sodium prevents asthma attacks by blocking what?

Answer 26

bronchoconstriction caused by antigen inhalation, exercise, aspirin, and environmental toxins

Question 27

How does Xolair work?

Answer 27

Inhibits binding of IgE antibodies to the Fc(epsilon)R1 Receptor on mast cells and basophils inhibiting degranulation

Question 28

What is an important AE of Zileuton?

Answer 28

- Doubles the blood levels of theophylline | - Causes increase in prothrombin time of patients taking warfarin

Question 29

What 4 drug classes can be used to treat COPD?

Answer 29

- Inhaled muscarinic receptor antagonists - Long-acting beta2-adrenergic agonists - Short-acting beta2-adrenergic agonists - Alpha1-antitrypsin replacement (rare)

Question 30

What are 2 muscarinic antagonist medications?

Answer 30

Ipratropium and Tiotropium | Quaternary ammonium compounds that limit systemic absorption

Question 31

What 3 things happen during lung remodeling in COPD?

Answer 31

- Fibrosis of small airways - Hyperinflation of lungs (alveolar wall destruction) - Mucus hypersecretion

Question 32

What genetic deficiency occurs in <1% of COPD patients?

Answer 32

Alpha 1 antitrypsin

Question 33

What medications are used to treat alpha 1 antitrypsin deficiency?

Answer 33

- Prolastin - Aralast - Zemaria

Question 34

Where is the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) expressed?

Answer 34

- Airway epithelium - Sweat duct epithelium - Pancreatic duct epithelium

Question 35

What happens to the CFTR protein in most CF cases?

Answer 35

Defective processing - it never reaches the membrane surface

Question 36

What drug is used to treat CF in the small subset of patients?

Answer 36

Ivacaftor

Question 37

What drug classes are used to treat CF in the majority of patients?

Answer 37

Mucolytics (Dornase alfa, Pulmonase, Mucomyst, Hypersal) Bronchodilators (albuterol) Antibiotics (Tobramycin and azithromycin)