Drugs for COPD and Asthma

Question 1

What are the two treatment approaches to COPD and asthma?

Answer 1

1. Bronchodilation - via relaxation of airway smooth muscle (i.e. beta agonists)
2. Anti-inflammation - reverse airway mucosal thickening caused by edema and cellular infiltration (i.e. corticosteroids)

Question 2

What are the two types of asthma and which is associated with allergy?

Answer 2

1. Early onset asthma or extrinsic asthma - associated with allergy in young children
2. Late onset asthma or intrinsic asthma - non-specific factors, stress, or severe exertion

Question 3

How does binding of the beta-2 receptor result in relaxation of airway smooth muscle?

Answer 3

Gs protein triggers increase in cAMP. cAMP promotes phosphorylation of MLCK to inactive form. If MLCK is inactive, it cannot cause contraction of smooth muscle

Question 4

How do the M3 receptors in the lungs cause bronchoconstriction and increased mucus secretion?

Answer 4

Gq mechanism causes increase in Ca+2, which binds calmodulin and activates MLCK which causes bronchiolar contraction.

Question 5

Other than increasing bronchiolar relaxation, how does cAMP increase benefit patients in acute asthmatic attacks?

Answer 5

Inhibits the exocytosis of histamine from mast cells and basophils (cGMP will increase the exocytosis)

Question 6

Why is alpha receptor activation of epinephrine actually good in anaphylaxis?

Answer 6

Constricts the bronchial mucosal vessel and decreases the blood flow, preventing the mucosal gland from overacting and decreasing congestion / edema

Question 7

What are the short-acting Beta-2 agonists of consequence?

Answer 7

Albuterol
Levalbuterol (R-isomer)
Pirbuterol
Terbutaline

Question 8

What are the long-acting Beta-2 agonists of consequence?

Answer 8

Formoterol
Salmeterol
Olodaterol

Question 9

When is it good to use a beta-2 agonist vs a corticosteroid?

Answer 9

Beta-2 agonist - only during exacerbations (bronchospasm) or at low levels in combined therapy with corticosteroid

Corticosteroid - Long-term control to prevent exacerbation, or at very high levels in life threatening situations (not good for acute attack)

Question 10

What are the two cholinergic antagonists used for asthma control and why are they used?

Answer 10

1. Ipratropium
2. Tiotropium (longer-acting)

Used in asthma exacerbations when patient is on a beta-blocker or can’t tolerate beta-2 agonists

Question 11

What is the mechanism of action of Xanthines? Give an example

Answer 11

Inhibit phosphodiesterase, increasing cAMP levels

Example: Theophylline

Question 12

What are the 5 stages of asthma?

Answer 12

1. Mild
2. Moderate
3. Severe
4. Hypoxemia
5. Respiratory acidosis

Question 13

In what stage of asthma are Xanthines used?

Answer 13

Can be used in all stages, may be given IV in later stages. Generally has a synergistic effect with beta-2 agonists.

Question 14

Why should you use xanthines cautiously? What drug-drug interaction do you worry about most?

Answer 14

Very narrow therapeutic range, can give high probability of seizure and cardiac stimulation which causes arrhythmia and fatal cardiac arrest

Most likely to accumulate due to structural analog -> caffeine

Question 15

What are the three drugs which have the highest efficacy in long-term corticosteroid management of asthma?

Answer 15

1. Fluticasone
2. Budesonide

First two are fluorinated to have longer action and less systemic effects

3. Ciclesonide

Question 16

Why is Ciclesonide juicy?

Answer 16

It is activated by two enzymes that are only expressed in upper and lower airway epithelium limiting adverse effects

Question 17

What are combination inhalers?

Answer 17

Corticosteroid combined with long-acting beta-2 agonist -> not recommended in children less than 12 years old

Question 18

Why drug is super efficacous in the treatment of mild to moderate extrinsic asthma? How is it taken?

Answer 18

Cromolyn sodium -> prevents mast cell degranulation

Taken via inhalation

Question 19

What are the leukotriene receptor blockers used only for extrinsic asthma?

Answer 19

1. Montelukast (Taken orally)
2. Past: Zafirleukast -> too many drug-food interactions

Treatment of allergic rhinitis

Question 20

What is the anti-IgE monoclonal antibody which may be injected and when is it used?

Answer 20

Omalizumab

Used for those with moderate to severe extrinsic asthma whose symptoms are not adequately controlled by inhaled corticosteroid