Asthma Pharmacology

Question 1

What are the causes of airway narrowing in acute ashtma?

Answer 1

Constriction of smooth muscle
inspissation of viscid mucous plugs
Thickening of bronchiole mucosa due to edema, infiltration, and hyperplasia

Question 2

What cause is most easily reversed?

Answer 2

Smooth muscle constriciton (by B-androceptor stimulants)

Question 3

How is long term control of asthma most readily acheived

Answer 3

Inhaled corticosteroid

Less effectively with LT pathway antagonist or mast cell stabilizer

Question 4

What is the pathogenesis of Asthma?

Answer 4

Allergens provoke IgE production, IgE binds to mast cells on re-exposure crosslinks are formed causing mast cell degranulation releasing histamine, tryptase, LTC4, LTD4 and PGD2

Question 5

Characterize the asthmatic response

Answer 5

Early asthmatic response is acute bronchoconstriction, often it is followed in 3-6 hours by the late asthmatic response which is the result of the influx of inflammatory cells that may hypersensitize the airway.
Mediators of the late response are thought to be controlled by TH2 mediated cytokines.

Question 6

How is broncial reactivity assessed?

Answer 6

Measuring drop in FEV1 after administration of serially strong doses of methacholine.

Question 7

What are the “relievers” of asthma?

Answer 7

Adrenoceptor agonists and sympathomimetic agents

Question 8

What are the controllers of asthma?

Answer 8

Inhaled corticosteroids and anti-inflammatory agents

Question 9

What are the general actions of adrenoceptor agonists?

Answer 9

Relax airway smooth muscle
Prevent mediator release
Increase heart rate
Causes skeletal muscle tremors

Question 10

Why are isoproterenol and epinephrine reserved for special situations?

Answer 10

Because they increase the heart rate through stimulation of B1

Question 11

What is the best method of delivery for B-agonists?

Answer 11

Inhalation
Most direct action, least systemic toxicity
80-90% still lost to mouth and pharynx
Slow inhalation and breath holding for five seconds maxiize dose response

Question 12

What B agonists are rarely used for asthma?

Answer 12

Epinephrine, ephedrine, and isoproterenol

Question 13

What is the mechanism of antimuscarinic agents?

Answer 13

Inhibit acetylcholine

Question 14

What is the mechanism of theophylline?

Answer 14

Inhibits PDE, keeping cAMP active leading to continuous bronchodilation.
Most commonly affects PDE4 whose inhibitions causes decreases release of cytokines

Question 15

What is the mechanism of B-agonists?

Answer 15

Stimulate cAMP through B2 receptors

Question 16

What are the primary B2 selective agonists?

Answer 16

Albuterol, terbutaline, metaproterenol, pirbuterol

All have large substitutions near the amino and hydroxyl group

Question 17

What are salemeterol and formoterol?

Answer 17

Long acting B2 selective agonists, salmeterol is a partial B agonist
Both have a high lipid solubility which permits them to dissolve in smooth muscle in high concentrations
They interact with inhaled corticosteroids to improve asthma control.
o antiinflammatory action so they are not recommended for monotherapy

Question 18

What are the important methylxanthines?

Answer 18

Theophylline, theobromine, and caffeine

Aminophylline is the theophylline prep commons used for therapeutic purposes

Question 19

What is the function of antimuscarinic agents in acute bronchospasm?

Answer 19

They are less effective than B-agonists but can add to bronchodilation when co-administered

Question 20

What is the mechanism of corticosteroids?

Answer 20

Broad anti-inflammatory activity
No direct relaxation of smooth muscle but reduce bronchial reactivity
Potentiate B agonist activity

Question 21

How are corticosteroids administered?

Answer 21

Usually by inhalation (fluticasone 4x daily)

Oral and parental are usually reserved for severe situations in order to avoid systemic effects.

Question 22

What is ciclesonide?

Answer 22

Oral corticosteroid given as a prodrug that is activated in the bronchial epithelial cells
When in the serum it is tightly bound to proteins so it does not have access to other receptors

Question 23

What is the effect of leukotriene inhibitors?

Answer 23

They inhibit the lipoxygenase pathway or block the LTB4 receptor which leads to a decrease in the production of inflammatory cytokines and chemokines.
Have suffix Kast
Taken orally

Question 24

What is the mechanism of aspirin-induced asthma?

Answer 24

Cox inhibitors shunt the metabolism of arachadonic acid toward Lipoxygenase pathway which increases Leukotrienes and causes inflammatory exacerbation.
Blocked by inhibitors of Lox

Question 25

What is advair and for what is it prescribed?

Answer 25

Cobination of salmetoral and fluticason

Indicated for patients who are failing on long term corticosteroid therapy