Asthma & COPD

Question 1

Compared to epinephrine, this sympathomimetic drug has longer duration, less potency, and more pronounced central effects.

Answer 1

ephedrine

Question 2

This sympathomimetic is valued in anaphylactic patients with acute vasodilation, shock, and bronchospam

Answer 2

epinephrine

Question 3

LABAs have this structural property

Answer 3

longer side chain

can interact with multiple receptor sites

Question 4

B2 agonist available as SC injection

Answer 4

terbutaline

Question 5

LABAs:

Answer 5

salmeterol, formoterol

Question 6

B2 agonists available in tablet form

Answer 6

albuteral/salbutamol, terbutaline

2-3x daily

Question 7

Full LABA?

Answer 7

formoterol

F=Full

Question 8

Partial LABA?

Answer 8

salmeterol

Question 9

LABA are not recommended for monotherapy for asthma because:

Answer 9

They lack anti-inflammatory properties.

Question 10

Ultra LABA

Answer 10

indacaterol

Question 11

R-isomer of B2 agonists do what?

S-isomer?

Answer 11

R-isomer = activate receptor
S-isomer = promotes inflammation

Question 12

B2 selectives inhibit production of ____ (it decreases cAMP level) which was shown to be elevated in asthmatic subjects and patients with other inflammatory lung disorders

Answer 12

endothelin-1

inhibiting ET-1 therefore increases cAMP levels

Question 13

How do B2 selectives INCREASE expression of glucocorticoid receptors?

Answer 13

Inc. cAMP –> activate PKa –> activate CREB –> DNA-level transcription

Question 14

B2 receptor polymorphism associated with increased agonist-mediated responsiveness and less reactive airways.

Answer 14

Glu27

Less reactive asthma

Question 15

B2 receptor polymorphism associated with enhanced agonist-mediated DESENSITIZATION

Answer 15

Arg16

Increased asthma severity, reduced response to bronchodilators

Question 16

B2 receptor polymorphism associated with increased airway hyperreactivity, NOCTURNAL symptoms and more severe asthma

Answer 16

Gly16

Question 17

R isomer of albuterol that is more active and produces greater bronchodilation over a longer period of time

Answer 17

levalbuterol

more affinity
higher profile of metabolism
does not contract airway smooth muscle

Remember that S isomers PROMOTE inflammation. However, lack of evidence as far as efficacy and patient outcomes.

Question 18

Combination of active groups of salbutamol/albuterol with theophyline

Answer 18

reproterol

salbutamol increases cAMP
theophylline decreases cAMP breakdown by inhibiting PDE

Question 19

B2 agonist that interacts with a receptor-specific auxiliary binding site

Answer 19

salmeterol

Question 20

B2 agonist with direct activation of receptor

Answer 20

albuterol

Question 21

B2 agonist taken up into a membrane depot to activate receptor

Answer 21

formoterol

Question 22

B2 agonists increase effects of (drug interaction)

Answer 22

TCA
MAOi
sympathomimetics

Question 23

In severely ill patients on B2 agonists, what must be monitored in order to prevent respiratory paralysis

Answer 23

hypokalemia

Question 24

First line drug for COPD

Answer 24

ipratropium

Question 25

MoA of ipratropium

Answer 25

blocks ACh in bronchial smooth muscle inhibits stimulation of M1, M2, M3 --> decreased secretion, increased bronchodilation

Question 26

Anti-musc with subtype-selectivity M3, M1 > M2

Answer 26

tiotropium

Question 27

Anti-musc with less frequent adverse effects

Answer 27

tiotropium

Question 28

Anti-musc that can cause dyspepsia, vomiting, GERD

Answer 28

tiotropium

Question 29

Non-selective PDE inhibitor used for asthma

Answer 29

theophylline

Question 30

theophylline MoA

Answer 30

blocks PDE --> inc. cAMP (i.e., decreasing cAMP hydrolysis) --> ++ Ca influx --> epi release --> bronchodilation and anti-inflammation Adenosine receptor blockage --> blocks Gq coupled receptor that causes bronchoconstriction Basically: blocks PDE and adenosine

Question 31

Common theophylline ADR at 2-35 mcg/L

Answer 31

tachycardia

Question 32

Common theophylline ADR at >35

Answer 32

seizure

Question 33

theophylline is metabolized by

Answer 33

CYP450

Question 34

theophylline decreases levels of these drugs (via induction)

Answer 34

``` barbiturates carbamazepine charcoal rifampicin ketoconazole sympathomimetics ```

Question 35

theophyilline increases levels of these drugs

Answer 35

``` allopurinol B blockers CCB ciprofloxacin INH macrolides ```

Question 36

Theophylline's effect on cor pulmonale

Answer 36

increases

Question 37

These drugs inhibit (virtually all) cytokine synthesis, inactivate NF-KB (a transcription factor that induces production of TNF-a), other inflammatory agents

Answer 37

corticosteroids beclomethasone prednisone fluticasone

Question 38

Prodrug activated by cleavage of esterases in bronchial epithelial cells. Less unwanted effects and no interaction with skin, eye, bone (tightly bound to serum proteins)

Answer 38

ciclesonide

Question 39

How does cAMP prevent smooth muscle contraction

Answer 39

PKA phosphorylates myosin light chain kinase MLCK (inactivating) --> no contraction

Question 40

5-LOX pathway inhibitor

Answer 40

zileuton blocks conversion of arachidonic acid to LTs For prevention not reversal. Liver toxicity.

Question 41

Blocks leukotriene receptor. Less effective than ICS.

Answer 41

montelukast | also zafirlukast

Question 42

Widely used in aspirin-induced asthma

Answer 42

montelukast

Question 43

Prevents degranulation of MAST CELLS

Answer 43

cromolyn Prevention not reversal.

Question 44

Cromolyn is more useful in the prevention of what?

Answer 44

allergic asthma

Question 45

Inhibits the binding of IgE to high-affinity IgE receptor on mast cells, basophils, dendritic cells

Answer 45

omalizunab

Question 46

B2 agonist + Inhaled CS combinations: (3 of them)

Answer 46

salmeterol + fluticasone formoterol + budesonide salbutamol + beclomethasone

Question 47

Gold standard of asthma gadgets

Answer 47

MDI