Treating Asthma

Question 1

Which disease is the leading cause of lost school days in children and work days among adults is what?

Answer 1

asthma

Question 2

How do we differentiate mild from severe asthma?

Answer 2

• mild: occasional symptoms, usually upon some sort of exposure
• sever: frequent attacks, especially at hight, which limit activity

Question 3

Describe airway changes in those suffering an asthma attack.

Answer 3

• bronchial and tracheal constriction
• mucosal thickening from edema and cellular infiltration
• the net result is narrow airways filled with thick mucous plugs

Question 4

During an asthma attack, what measures of airflow are likely to be reduced?

Answer 4

all indices of expiratory flow:

• FEV1
• FVC
• FEV1/FVC
• peak expiratory flow rate

Question 5

What is FEV1?

Answer 5

the volume of air expired in the first second of forced expiration

Question 6

What is FVC?

Answer 6

the volume breathed out from a maximally forced expiratory effort

Question 7

During an asthma attack, which measures of airflow are likely increased?

Answer 7

• total lung capacity
• functional residual capacity
• residual volume
• DLCO (diffusion capacity for CO)

Question 8

What is the difference between functional residual capacity and residual volume?

Answer 8

• functional residual capacity is the residual volume left during normal breathing
• residual volume is the residual volume left after maximally forced expiratory effort

Question 9

What role do bronchodilators and anti-inflammatory agents play in the treatment of asthma?

Answer 9

• bronchodilators are short-term relievers

- anti-inflammatory agents are long-term controllers

Question 10

How does the airway of an asthmatic individual differ from that of a healthy individual?

Answer 10

the airway of an asthmatic is hyper-responsive to inflammatory mediators released in response to allergens, cold, exercise, etc.

Question 11

Which inflammatory cells are involved in the early and late phase of an asthma attack?

Answer 11

• early: primarily mast cells

- late: T-cells, mast cells, eosinophils, and neutrophils

Question 12

Why do severe asthmatics often experiences more symptoms at night?

Answer 12

because PNS tone is highest at night, which means that bronchoconstriction is more likely

Question 13

How is bronchoconstriction mediated by the autonomic nervous system?

Answer 13

vagal efferents release acetylcholine onto muscarinic receptors on bronchial smooth muscle

Question 14

Through what two mechanisms can inhaled irritants cause bronchoconstriction?

Answer 14

• they can induce release of chemical mediators from mast cells
• they can stimulate afferent vagal nerves to initiate reflex bronchoconstriction

Question 15

What second messenger system regulates bronchial tone?

Answer 15

cAMP

Question 16

Through what mechanism does the sympathetic nervous system act on bronchial smooth muscle?

Answer 16

• B2-adrenergic receptors are activated, activating AC

- cAMP levels rise and induce bronchodilation

Question 17

Do high intracellular cAMP levels support bronchodilation or bronchoconstriction?

Answer 17

bronchodilation

Question 18

What role does PDE play in regulating bronchial tone?

Answer 18

it degrades cAMP, promoting bronchoconstriction

Question 19

How do phosphodiesterase inhibitors function in the treatment of asthma?

Answer 19

they inhibit the degradation of cAMP, promoting bronchodilation

Question 20

How does theophylline function in the treatment of asthma?

Answer 20

it is an adenosine receptor antagonists that inhibits adenosine from inducing bronchoconstriction

Question 21

Name two molecular signals that serve to initiate bronchoconstriction.

Answer 21

• acetylcholine

- adenosine

Question 22

Bronchodilators fail to treat what aspect of asthma pathology?

Answer 22

mucous formation, edema, and cellular infiltration

Question 23

Why are inhaled B2 agonists like albuterol relatively safe with few side effects?

Answer 23

• because inhalation, if done correctly, is essentially a topical administration without systemic effects of the drug
• that which is swallowed is either poorly absorbed or subject to a high first pass effect

Question 24

What effect does albuterol have on potassium?

Answer 24

it increases insulin release and therefore induces a hypokalemia

Question 25

What role do sympathomimetics play in the treatment of asthma?

Answer 25

- selective B2 agonists like albuterol are first line therapy - however, less selective sympathomimetics like epinephrine and ephedrine have too many off target cardiovascular effects and are thus reserved for resolution of severe attacks

Question 26

Drugs ending in the suffice "-phylline" are part of what class?

Answer 26

the methylxanthine bronchodilators

Question 27

Why aren't muscarinic antagonists a first line therapy for acute asthma given their bronchodilator effects?

Answer 27

because they have unpredictable efficacy due to varying involvement of parasympathetics in the bronchospasm of different people

Question 28

What role do muscarinic antagonists play in the treatment of asthma?

Answer 28

- they relax bronchial smooth muscle and decrease mucus secretion - however, they are only effective in those for whom parasympathetic involvement contributes significantly to their bronchospasms - most useful for those with symptoms at night (symptoms often induced by increased PNS tone)

Question 29

Through what mechanism of action do glucocorticoids function in the treatment of asthma?

Answer 29

- they inhibit the production of inflammatory cytokines | - they have no direct effect on bronchodilation

Question 30

List three benefits of using glucocorticoids in those with asthma?

Answer 30

- reduce bronchial reactivity - increase airway caliber by reducing edema - reduce frequency of attacks

Question 31

Many asthmatics require daily corticosteroids to prevent asthma attacks. How do we avoid the systemic symptoms of these treatments?

Answer 31

by prescribing inhaled corticosteroids

Question 32

What are the side effects that accompany long-term inhaled corticosteroid use?

Answer 32

oropharyngeal candidiasis or hoarseness from vocal cord irritation

Question 33

Drugs with the suffix "-lukast" act in what way?

Answer 33

they are leukotriene inhibitors used in the treatment of asthma

Question 34

What role do leukotrienes play in asthma?

Answer 34

they especially help mediate the late phase of asthma - LTB4 is a chemoattractant for eosinophils, monocytes, and neutrophils - LTC4 and LTD4 are eosinophil chemoattractants, potent broncho-constrictors, and promoters of vascular permeability and mucous secretion

Question 35

What is zileuton?

Answer 35

a 5-lipoxygenase inhibitor which impairs leukotriene synthesis and is used in the treatment of asthma

Question 36

Leukotriene antagonists are most specific for which receptor?

Answer 36

the LTD4 receptor

Question 37

What is omalizumab?

Answer 37

- an antibody against IgE, which inhibits binding of IgE to mast cells (doesn't inactivate already bound IgE) - lowers plasma IgE levels and reduces bronchospasms - lessens asthma severity and reduces the need for corticosteroids

Question 38

Which two monoclonal antibody drugs are useful in the treatment of asthma? What do they target?

Answer 38

- omalizumab: anti-IgE | - mepolizumab/reslizumab: anti-IL-5

Question 39

What role do mepolizumab and reslizumab play in the treatment of asthma?

Answer 39

- inhibit binding of IL-5 to mast cells - reduces severe asthma attacks by reducing number of eosinophils in the blood - used for refractory asthma

Question 40

What is the goal of asthma prophylaxis treatments?

Answer 40

reduce mast cell degranulation, thereby reducing the number of asthma attacks

Question 41

What is cromolyn sodium?

Answer 41

a drug used to stabilize mast cells and prevent degranulation, thereby inhibiting asthma attacks

Question 42

When are asthma prophylactic drugs used?

Answer 42

just before exercise or allergen exposure

Question 43

For what kinds of asthma are prophylactic drugs like cromolyn sodium best?

Answer 43

allergen- and exercise-induced asthma

Question 44

What is nedocromil sodium?

Answer 44

a mast cell stabilizer used as asthma prophylaxis

Question 45

How do asthma prophylactics differ from daily anti-inflammatory drugs?

Answer 45

- prophylactics offer acute protection when an exposure is expected soon - anti-inflammatory drugs are used daily to reduce the responsiveness of the airway and to prevent asthma attacks or limit their severity all the time

Question 46

How do cromolyn sodium and nedocromil sodium stabilize mast cells?

Answer 46

- they alter delayed chloride channels in the cell membrane | - this inhibits mast cell activation and reduces release of histamine and other mediators

Question 47

How is cromolyn sodium administered?

Answer 47

via inhalation since it experiences poor GI absorption

Question 48

Describe the asthma treatment pyramid.

Answer 48

- offer a short-acting B2 agonist for symptom relief - add a low dose ICS - then add a long-acting B-agonist (oral formulation) - then increase the dose of ICS - finally, add an OCS if necessary