Pharmacology of Asthma

Question 1

Name 3 groups of medications used to control the symptoms of asthma.

Answer 1

1. Beta Agonists/Sympathomimetics
2. Muscarinic Agonists/Anticholinergics
3. Xanthines

Question 2

Name 3 classes of medications used to control and prevent future asthma exacerbations.

Answer 2

1. Corticosteroids
2. Antileukotrienes
3. Anti-IgE Ab

Question 3

What medication do you use to diagnose asthma?

Answer 3

Methacholine “Challenge”

Question 4

Corticosteroids

Mechanism of Action

Answer 4

target is glucocorticoid receptor in cytoplasm

(1) inhibits phospholipase A2

decreases synthesis of all cytokines (PGEs, LTs)

(2) inactivates NF-κB

decreases transcription of TNF–α & other cytokines

(3) stimulates synthesis β2R in lung, nasal mucosa

co-administer with long-acting β2 agonists (prevents downregulation of β2R via β2 agonists)

Question 5

Oral Corticosteroid

Use and Toxicity

Answer 5

severe acute exacerbations (IV)

1st line therapy for chronic asthma (PO)

weight gain (nuchal hump, moon facies), mood alteration, muscle twitches, insomnia, bulging eyes

Question 6

Inhaled Corticosteroids

Use and Toxicity

Answer 6

1st line therapy chronic asthma

slow onset (MDI)

glaucoma, cataracts, osteoporosis, oral candidiasis, dysponia (hoarsness)

Question 7

Prednisone

Methylprednisolone

Answer 7

oral corticosteroids

Question 8

Beclomethasone

Answer 8

inhaled corticosteroid

Question 9

Fluticasone

Answer 9

inhaled corticosteroid

Question 10

Budesonide

Answer 10

inhaled corticosteroid

Question 11

Antileukotrienes

Use and Toxicity

Answer 11

exercise-/aspirin-induced asthma

can be combines with corticosteroids (PO)

monitor hepatic enzymes

moderate CYP1A2 inhibitor

Question 12

Montelukast

Answer 12

block leukotriene receptors (LTD4 receptor)

bronchodilation + anti-inflammatory

Question 13

Zafirlukast

Answer 13

block leukotriene receptors (LTD4 receptor)

bronchodilation + anti-inflammatory

Question 14

Zileuton

Answer 14

inhbits 5-lipoxygenase pathway

blocks arachidonic acid -> leukotrienes

LTB4 = attracts neuts; LTC/D4 = bronchoconstrict

Question 15

Omalizumab

Answer 15

allergic asthma resistant to inhaled steroids and long-acting β-agonists

monoclonal anti-IgE Ab

binds unbound serum IgE, blocks IgE from binding to FcεRI on mast cells

eventually decreases levels of circulating IgE

subcutaneous injection, expensive

URI, headaches

Question 16

Name the non-selective B agonists and their toxicity.

Answer 16

Epinephrine, Isoprotenerol

tachycardia, arrhythmia, angina

Question 17

Selective Beta Agonist Mechanism of Action

Answer 17

relaxes bronchial smooth m. (β2)

bind Gs -> increase cAMP -> bronchodilation

other effects - increase surfactant, decrease mediator release, decrease microvasculature leakage

Question 18

Short-Active B Agonist

Use and Toxicity

Answer 18

1st line for acute exacerbations

(MDI, nebulizer)

β1 (&α) agonism - HTN, angina, vomiting, vertigo, CNS stimulation, dryness/irritation of oropharynx

Question 19

Long-Acting Beta Agonist

Use and Toxicity

Answer 19

1st line prophylaxis chronic asthma

50X more selective than albuterol

coughing, tremor, arrhythmia, angina, headaches, hives, hypoK

Question 20

Name the SABAs

Answer 20

Albuterol

Terbutaline

Metaproterenol

Question 21

Name the LABAs

Answer 21

Salmeterol

Formoterol

Question 22

Name the three muscarinic antagonists, their uses, and relative toxicities.

Answer 22

Atropine - many systemic side effects

Ipratropium - short-acting

Tiotropium - long-acting

Iprotropium and Tiotropium have rare side effects - dry mouth, dry bronchial secretions, urinary retention.

Question 23

Xanthines

Mechanism of Action

Use and Toxicity

Answer 23

(1) inhibits phosphodiesterase

increases cAMP (via decrease in cAMP hydolysis)

promotes bronchodilation

(2) blocks actions of adenosine

decreases bronchoconstriction

Use w/ asthma refractive to other medications; use is limited due to narrow therapeutic index.

cardiotoxicity, neurotoxicity

toxicity especially <1 yr olds

(hypoTN, seizures, arrhythmias, nervousness and tremor)

*Many drug intercations - metabolized via cytochrome P450

Question 24

Theophylline

Answer 24

aka aminophylline

xanthine

Question 25

name two xanthines not used clinically

Answer 25

caffeine and theobromine