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Asthma, COPD, Rhinitis > Asthma > Flashcards

Asthma Flashcards

1
Q

What are common symptoms of asthma?

A

coughing

Wheezing

Chest tightness

SOB

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2
Q

What are the general mechanisms responsible for asthma (the “immunologic disease”)?

A

1) obstructive lung disease = bronchoconstriction

2) inflammation of the airway wall = airways respond to inflammation by airway edema, mucus secretion..

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3
Q

How does mast cell sensitization occur?

A

(1) exposure to antigen will induce systemic generation of antibodies by B cells and TH2 helper cells
(2) IgE antibodies will become fixated on the surface of the mast cell
(3) When antigens bind the antibody, degranulation follows

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4
Q

What mediators do mast cells release?

A

Histamine

Proteases

Heparin

Leukotrienes

Prostaglandins

Platelet activating factor (PAF)

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5
Q

What are preformed vs. lipid-derived mast cell mediators?

A

Preformed = immediate onset = histamine, protease

Lipid-derived = slower onset but LONGER duration = heparin, leukotrienes, Prostaglandins, PAF

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6
Q

Which are potent bronchoconstrictors?

A

Lipid-derived mast cell mediators

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7
Q

What effects do histamine have?

A

Vasodilation

Vasopermeability

Itch

Cough

Bronchoconstriction

Rhinorrhea

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8
Q

How does the second mechanism (inflammation of the airway wall) come about?

A

Immune cells get recruited during asthmatic inflammation

Their mediators are inflammatory and cause injury/inflammation in the airways

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9
Q

What is non-allergic asthma?

A

Inhaled irritants induce bronchoconstriction

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10
Q

What are 3 major pathways for treating asthma?

A

(1) anti-IgE therapy
(2) target inflammation with beta2 agonists, leukotriene modifiers, corticosteroids, or theophylline, anti-IgE therapy
(3) target bronchoconstriction with beta2 agonists, leukotriene modifiers, muscarinic receptor antagonists, theophylline

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11
Q

What is an advantage of aerosol delivery of drugs?

A

Produces high local concentration in the lungs with low systemic delivery

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12
Q

What drugs is aerosol delivery the main route for?

A

Beta2 adrenergic receptor agonists

Glucocorticoids

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13
Q

What are glucocorticoids used for asthma?

A

Maintenance therapy = reduces inflammation

Administered prophylactically !!!

Does NOT relax airway SM though

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14
Q

What are some examples of inhaled corticosteroids?

A

Beclomethasone

Triamcinolone

Flunisolide

Fluticasone

Budesonide

Fluticasone + salmeterol

Budesonide + formoterol

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15
Q

What’s the MOA for ICS?

A

Target lung inflammation

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16
Q

What are some side effects of ICS?

A

Oropharygneal candidiasis

Dysphonia

Modest decreases in bone density

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17
Q

What second messenger promotes bronchodilation?

A

Increased cAMP

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18
Q

What effect do beta2 adrenergic agonists have?

A

Bronchodilation

Activation of the receptor stimulates Gs and increases cAMP to relax bronchial SM

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19
Q

What effects do beta2 agonists have on inflammatory cells?

A

Stimulation of beta2 receptors on mast cells leads to increased cAMP and decreased mast cell degranulation

Cytokines production is impaired
Immune cell function is inhibited

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20
Q

What is a potential problem of beta2 adrenergic agonists?

A

Desensitization can occur = prolonged stimulation leads to loss of responsiveness, receptor downregulation

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21
Q

What are beta2 receptor agonists used for?

A

Rescue therapy!

Relief of acute bronchospasm

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22
Q

What are examples of beta2 adrenergic agonists?

A

Metaproterenol

Albuterol

Salmeterol

Terbutaline

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23
Q

Which is a SABA and which is a LABA?

A

SABA = short acting beta2 agonist = albuterol

LABA = salmeterol

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24
Q

What are side effects associated with beta2 adrenergic agonists?

A

Tremor

Hypokalemia

Tachycardia

Anxiety

Insomnia

Palpitations

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25
Q

Compare SABAs versus LABAs.

A

SABAs = effective for rescue therapy and for preventing exercise-induced asthma

LABAs = used in combination with ICS

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26
Q

What is a concern with LABAs?

A

Can lead to beta2 adrenergic receptor desensitization, downregulation

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27
Q

How do muscarinic antagonists work?

A

Block vagal nerve mediated bronchoconstriction and bronchial secretions mediated by ACh on SM

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28
Q

What are important examples of muscarinic antagonists?

A

Ipratropium = only COPD

Tiotropium = both COPD + asthma

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29
Q

What are some side effects of muscarinic antagonists?

A

Dry mouth

Urinary retention

Constipation

Tachycardia

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30
Q

What are important examples of leukotriene modifiers?

A

Zileuton

Montelukast

Used prophylactically in treatment of mild asthma

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31
Q

What are side effects of leukotriene modifiers?

A

Hepatotoxicity (liver function tests)

Rare Chung-Strauss syndrome (allergic response that can be fatal)

32
Q

How do Cromolyns work?

A

Inhibit mast cell degranulation

Used prophylactically for maintenance therapy

33
Q

What promotes bronchoconstriction?

A

Adenosine receptor activation

ACh

34
Q

What facilitates bronchodilation?

A

Increased cAMP

35
Q

Theophylline is an example of what?

A

Methylxanthines

36
Q

How do methylxanthines work?

A

Adenosine receptor antagonists

Inhibit PDE, leading to increased cAMP in SM and mast cells

37
Q

What effects do methylxanthines have?

A

Relaxation of SM (bronchodilation, vasodilation)

CNS stimulation

Diuretic effect

38
Q

What are side effects of methylxanthines?

A

CNS stimulation (convulsions)

Arrhythmias, tachycardia

Hypotension

39
Q

What is an important example of anti-IgE antibody?

A

Omalizumab

40
Q

How do humanize anti-IgE antibodies work?

A

Prevent sensitization and fixation of antibody on mast cell

NOT an acute bronchodilator

41
Q

For acute effect + rescue, what drug should be used?

A

SABA - to decrease bronchospasm since it’s short-acting

42
Q

For prophylaxis, anti-inflammatory effects, which drugs should be used?

A

Inhaled glucocorticoids (which can be combined with LABAs)

Leukotriene modifiers

Anti-IgE

43
Q

Which drugs are anti-inflammatory?

A

Glucocorticoids

Leukotriene modifiers

Cromolyns

Anti-IgE antibodies

44
Q

Which drugs are bronchodilators?

A

Beta2 adrenergic agonists

Muscarinic antagonists

Methylxanthines

45
Q

What receptors mediate bronchial smooth muscle constriction?

A

M3

LT-2

A1

46
Q

What is the first line drug for asthma?

A

Beta2 agonists - “-terol” drugs

47
Q

What two actions does theophylline have?

A

1) antagonist at Adenosine1 receptor (to block constriction of bronchial SM)
2) PDE inhibition - prevent degradation of cAMP to also help mediate SM relaxation

48
Q

What two actions do glucocorticoids have?

A

1) act at glucocorticoid receptor to affect gene transcription of inflammatory mediators
2) inhibits PLA2 = dec. arachidonic acid = decreased inflammation

49
Q

What treatment is the next step for an acute asthma exacerbation if there is no improvement following administration of inhaled beta agonist?

A

Systemic glucocorticoids

1) restore airway responsiveness to endogenous catecholamines and exogenous beta2 agonists
2) anti-inflammatory action delayed

50
Q

What are indications for salmeterol?

A

Long term asthma treatment

Long term COPD tx

51
Q

What are indications for fluticasone?

A

Long term asthma tx

Long term COPD tx

52
Q

What are indications for tiotropium?

A

Long term asthma tx

Long term COPD tx

53
Q

What are indications for theophylline?

A

Long term asthma tx

Long term COPD tx

54
Q

What are indications for ipratropium?

A

Acute asthma exacerbation

Long term asthma tx

Acute COPD exacerbation

Long term COPD tx

55
Q

What are indications for albuterol?

A

Acute asthma exacerbation

Long term asthma tx

Acute COPD exacerbation

Long term COPD tx

56
Q

What are indications for methylprednisolone?

A

Acute asthma exacerbation

Long term asthma tx

Acute COPD exacerbation

Long term COPD tx

57
Q

What are indications for cromolyn?

A

Long term asthma tx

58
Q

What are indications for montelukast?

A

Long term asthma tx

59
Q

What are indications for omalizumab?

A

Long term asthma tx

60
Q

What are indications for zileuton?

A

Long term asthma tx

61
Q

What are indications for roflumilast?

A

Long term COPD tx

62
Q

What is the MOA of zileuton?

A

Inhibits LOX = dec. leukotrienes = dec. inflammation (and dec. contraction)

63
Q

What is the MOA of montelukast?

A

Blocks Leukotriene receptor = dec. bronchial contraction

64
Q

What is the MOA of tiotropium and ipratropium?

A

Block M3 receptor = dec. bronchial contraction

65
Q

What is the asthma tx plan for intermittent asthma?

A

SABA taken PRN

66
Q

What is the tx plan for asthma affecting a patient more than 2x a week?

A

ICS (low dose)

67
Q

What are alternatives to ICS for patient on Step 2 of asthma treatment?

A

Cromolyn

“-lukasts”

Theophylline

68
Q

What is the tx plan for asthmatic with symptoms daily?

A

ICS (low dose) - no compromising!!

LABA

69
Q

What are alternatives for LABA for patient at step 3 of asthma tx plan?

A

Zileuton

“-lukasts”

Theophylline

70
Q

What is the tx plan for asthmatic suffering symptoms throughout the day (step 4)?

A

ICS (medium dose) - no compromising!

LABA

71
Q

What are alternatives for LABA at step 4 of asthma tx plan?

A

Zileuton

“-lukasts”

Theophylline

72
Q

What is the tx plan for step 5 of asthma plan?

A

ICS (high dose)

LABA

If theres an allergic component - consider omalizumab

73
Q

What is the treatment plan for asthmatic at step 6 of persistent asthma?

A

ICS (high dose)

LABA

Oral corticosteroid

**if allergic component, consider omalizumab

74
Q

What effect does stimulation of H1 receptors on arterioles, endothelial cells and venules have?

A

Arterioles = relaxation = inc. blood flow

Endothelial cells = contraction = SP release

Venules = contraction = edema

75
Q

What effect does SP release following flare in “triple response” have?

A

Vasodilation

76
Q

What does SP stand for? What is it?

A

Substance P

Vasodilatory peptide

Asthma, COPD, Rhinitis (2 decks)

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