Exam 4: Pulmonary Pharmacology Flashcards Preview

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Flashcards in Exam 4: Pulmonary Pharmacology Deck (94):
1

Pulmonary SNS innervation:

SNS fibers from thoracic ganglia innervating smooth muscles of bronchi, pulmonary blood vessels
Sympathetic tone: bronchodilation via β2 receptors

2

Pulmonary PSNS innervation:

Vagus nerve
Parasympathetic tone: bronchoconstriction via M3 receptors

3

β2 receptors in the lungs cause these effects (3):

Bronchodilation
Increased cAMP
Greater sensitivity to epi vs. norepi

4

NANC nerves & role:

Non-adrenergic, non-cholinergic; relax airway smooth muscle by releasing NO and VIP

5

M3 receptors in the lungs cause these effects (2):

Bronchoconstriction via IP3 --> ↑Ca2+
Increased mucus secretions

6

Effects of M3 stimulation on pulmonary blood vessels:

None

7

Asthma is:

Chronic inflammatory disorder of airways with increased responsiveness of tracheobronchial tree to stimuli

8

Characteristics of asthma obstruction:

Variable and reversible

9

Characteristics of airways during asthma:

Inflamed
Edematous
Hypersensitive to irritant stimuli

10

Cells activated in the bronchial mucosa by allergens:

Th2 lymphocytes (which release cytokines)

11

Mediator cells in asthma:

*Eosinophils*
*Mast cells*
Neutrophils
Macrophages
Basophils
T lymphocytes

12

Chemical mediators in asthma:

*Cytokines*
*Histamines*
*Interleukins 3-4-5*
*Leukotrienes*
Prostaglandins
Adenosine
Platelet activating factor

13

Atopic asthma:

Mediated by IgE

14

Goal of medications in asthma:

Flattening the response to mediators

15

Characteristics of COPD obstruction:

Non- or incompletely reversible

16

Causes (3) of cell damage in COPD:

Impaired lung parenchyma
Degraded matrix
Toxic action of macrophages and neutrophils

17

Changes to lung tissue in COPD:

Enlarged air spaces
Fibrosis
↑ mucus production

18

Steroid and bronchdilator efficacy in COPD:

Steroids: limited effect
Bronchodilators: modest role in breathlessness

19

Step 1 of airway outflow d/o treatment:

Short-acting bronchodilators

20

Step 2 of airway outflow d/o treatment:

Regular inhaled corticosteroid

21

Step 3 of airway outflow d/o treatment:

Long-acting bronchodilators

22

Step 4 of airway outflow d/o treatment:

Phosphodiesterase inhibitors
Methylxanthines
Leukotriene inhibitors

23

Step 5 of airway outflow d/o treatment:

Oral corticosteroid

24

Three classes of bronchodilators:

β-agonists
Anticholinergics
Methylxanthines

25

Short-acting β2-agonists:

Terbutaline
Albuterol
Levalbuterol
Salbutamol

26

Long-acting β2-agonist:

Salmeterol

27

Indication for long-acting β2-agonists:

Nocturnal asthma

28

Refresh: Stimulatory G-protein cascade?

Gαs → ↑cAMP → ↓Ca++

29

Onset of action of β-agonists:

Rapid; 15-30 min

30

Duration of action of β-agonists:

30-60 minutes
(Salmeterol up to 4 hours)

31

Indication for β-agonists:

Rescue inhaler

32

Delivery of β-agonists:

Inhalation/aerosol, powder or nebulized
Exception: terbutaline is SC

33

Side effects of β-agonists:

Tremor
↑ HR
Vasodilation
Hyperglycemia, hypokalemia (d/t insulin release), hypomag

34

Preferred β2-selective agonist:

Albuterol

35

Dosing of albuterol:

100 mcg/puff
2 puffs q4-6hr

2.5 - 5.0mg nebulized in 5ml saline

36

Duration of action of albuterol:

4 hours; some relief up to 8 hours

37

Anesthetic considerations for albuterol:

Additive effect with volatile anesthetics on bronchomotor tone

38

2 isomers of albuterol:

R-albuterol more β2 affinity
S-albuterol more β1 affinity

39

Side effects of albuterol:

Tachycardia
Hypokalemia

40

Anesthesia uses of albuterol:

4 puffs to blunt AW response to tracheal intubation in asthmatics

41

Dosage of metaproterenol:

No more than 16 puffs/day

42

Advantage of bitolterol:

Longer lasting
CV side effects rare

43

Dosage of bitolterol:

16-20 puffs/day
(270 mcg/puff)

44

Indications for terbutaline:

Asthma, esp. status asthmaticus
Preterm labor

45

Delivery of terbutaline:

Oral, SC, inhalation

46

Dosage of terbutaline:

SC: 0.25mg q15min (adult)
SC: 0.01 mg/kg (child)
MDI: 16-20 puffs/day
(200 mcg/puff)

47

Examples of long-acting β-agonists:

Salmeterol
Advair: fluticasone and salmeterol
Formoterol

48

Long-acting β-agonists are long acting because:

Lipophilic side chains resisting degradation

49

Duration of action of long-acting β-agonists:

12-24 hours

50

Indications for long-acting β-agonists:

Prevention, not flare-up

51

Indications for anticholinergics:

Treatment of COPD
Secondary tx for asthma (resistant to β-agonist or w/ cardiac disease)

52

Model of asthma exacerbation d/t viral infection:

Activated T-cell → eosinophilic activation → mediator release via degranulation → deposition on airway smooth muscle and stimulate PSNS bronchoconstriction

53

Classification of atropine:

Naturally occuring tertiary amide alklaoid

54

Dosing of atropine for asthma:

1-2mg neb in 3-5ml NS

55

Side effects of atropine:

Tachycardia
Nausea
Dry mouth
GI upset

56

Classification of ipratropium bromide:

Quaternary ammonium salt derived from atropine

57

Dosing of ipratropium bromide:

40-80mcg in 2 puffs MDI or via neb

58

Onset of ipratropium bromide:

Slow; 30-90 min

59

Duration of action of ipratropium bromide:

4-6 hours

60

Absorption of ipratropium bromide relative to atropine:

Not significantly absorbed, so less cardiac/systemic side effects

61

Side effects of ipratropium bromide:

If inadvertently orally ingested, dry mouth/GI upset

62

Structure of tiotropium:

Quaternary ammonium salt

63

Duration of action of tiotropium:

Long acting

64

Advantage of tiotropium:

Not significantly absorbed so few systemic side effects

65

Indication for tiotropium:

COPD

66

MoA for methylxanthines:

Nonspecific inhibition of phosphodiesterase isoenzymes

67

Function of phosphodiesterase isoenzymes:

Prevent cAMP degradation → ↑cAMP → ↓Ca++ → bronchodilation

68

Indications for methylxanthines:

COPD/asthma

69

Examples of methylxanthines:

Theophylline
Aminophylline

70

Therapeutic plasma level of theophylline:

10-20 mg/ml

71

Toxic level of theophylline:

> 20 mg/ml

72

Toxic level of theophylline:

> 20 mg/ml

73

Drug interactions with theophylline:

Halothane (not in US)
Activates CYP450

74

Side effects of methylxanthines:

Arrythemias
N/V
Irritability
Insomnia
Seizures
Brain damage
Hyperglycemia
Hypokalemia
Hypotension

75

Indication for inhaled corticosteroids:

Major preventative treatment for asthma

76

MoA (3) of inhaled corticosteroids:

Alters genetic transcription to ↓ pro-inflammatory protein synthesis, ↑ anti-inflammatory proteins and β2 receptors
Induces apoptosis of inflammatory cells
Indirectly inhibits mast cells over time

77

Relative importance of inhaled corticosteroids for asthma mgmt:

Most important drug in the arsenal!!

78

Examples of inhaled corticosteroids:

Beclomethasone
Triamcinolone
Fluticasone
Budesonide

79

Anesthesia uses of inhaled corticosteroids:

Consider using 1-2 hours pre-op
Consider 5 day course of combined inhaled corticosteroids/albuterol to minimize risk of intubation bronchospasm

80

Drug interactions with inhaled corticosteroids:

Prolong the response of β-agonists (hence combination drugs like Advair)

81

% of inhaled corticosteroids that reach the airway vs. the oropharynx:

25% into airway
80-90% into oropharynx

82

Side effects of inhaled corticosteroids:

Osteopenia/porosis
Delayed growth in children
Oropharyngeal thrush
Hoarseness
Hyperglycemia

83

MoA of cromolyn:

Stabilizes mast cells and inhibits antigen-induced release of histamine
Inhibits the immediate allergic response to an antigen, BUT NOT the response once activated

84

Indications for cromolyn:

Prevention, not rescue!

85

Delivery of cromolyn:

Inhalation; 8-10% enters systemic circulation

86

Dosing of cromolyn:

4 times daily
7 days to effect!

87

Side effects of cromolyn:

Infrequent but serious:
Laryngeal edema
Angioedema
Urticaria
Anaphylaxis

88

Leukotrienes synthesized from:

Arachidonic acid in the presence of activated inflammatory cells

89

MoA of zileuton:

Blocks the biosynthesis of leukotrienes

90

Disadvantages of zileuton:

Low bioavailability
Low potency
Significant adverse effects
Hepatotoxic

91

MoA of monteleukast:

Blocks the Cysteinyl-Leukotriene 1 receptors on the smooth muscle

92

Drug interaction with monteleukast:

Coadministration with warfarin can prolong PT

93

MoA of omalizumab:

Short-term: Binds to IgE antibodies and prevents their binding to mast cells to mitigate the acute response to inhaled allergen

Long-term: IgE receptors on mast cells/basophils/dendritic cells are down-regulated

94

Delivery of omalizumab:

Given SQ for 2-4 weeks or parenterally infused; during early and late phase of asthmatic response