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Clinical Pharmacology II > Asthma/COPD > Flashcards

Asthma/COPD Flashcards

1
Q

What is asthma?

A

Disease of inflammation due to allergen exposure

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2
Q

What causes the reduced airway in asthma?

A

Smoot muscle thickening causing bronchoconstriction

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3
Q

What are the inflammatory mediators of asthma?

A 
EOSINOPHILS
neutrophils
mast cells
CD4 cells
IL-5
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4
Q

What are the symptoms of asthma?

A

Episodic shortness of breath
Wheeze
Cough
Chest tightness

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5
Q

What happens to the lungs in asthma after treatment?

A

reversible lung function

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6
Q

What is COPD?

A

disease of inflammation due to irritation

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7
Q

What causes the reduced airway in COPD?

A

Cellular damage by external irritants

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8
Q

What are the inflammatory mediators of COPD?

A

NEUTROPHILS
macrophages
CD8 cells

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9
Q

What are the symptoms of COPD?

A

Chronic cough
sputum production
DOE

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10
Q

What happens to the lungs in COPD after treatment?

A

irreversible lung function

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11
Q

What is the pathophysiology of asthma?

A

Airway inflammation
Airflow obstruction
Bronchial hyperresponsiveness

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12
Q

What is the early response of asthma and what do we treat it with?

A

Mast cell degranulation causes release of mediators which causes smooth muscle contractions and vascular leakage

Treat with bronchodilator

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13
Q

What is the late response of asthma and what do we treat it with?

A

3-6 hours after allergen exposure there is more sustained bronchoconstriction mediated by cytokines

Treat with inhaled corticosteroids

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14
Q

What is the pathophysiology of COPD?

A

Airway inflammation
Structural changes/”remodeling”
Mucociliary dysfunction

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15
Q

What happens to the lungs in COPD?

A

fibrosis and scarring
Alveolar damage
Mucus hypersecretion

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16
Q

What are the treatment approaches for asthma?

A 
Short-acting beta-2 agonist
Long-Acting beta-2 agonist
Inhaled or oral corticosteroid
Mast cell stabilizers
Leukotriene Antagonists
Methylxanthine derivatives
Immunotherapy
Long-acting antimuscarinics (LAMA)
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17
Q

What are the treatment approaches for COPD?

A 
Smoking Cessation
Short-acting beta-2 agonists
Long-acting beta-2 agonists
Short acting antimuscarinics (SAMA)
Long acting antimuscarinics (LAMA)
Inhaled or oral corticosteroids
Methylxanthine derivatives
Phosphodiesterase 4 (PDE-4) inhibitors
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18
Q

What is the common delivery system of asthma and COPD treatments?

A

Aerosolized systems

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19
Q

Why are aerosolized delivery systems prefered?

A

They deliver small particle sizes of the drug directly to the lung in high concentrations which will reduce the risk of systemic exposure

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20
Q

What are the drawbacks of using aerosolized delivery systems?

A

Requires proper technique for effective treatment

Expensive

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21
Q

What are the different aerosolized delivery systems?

A

Metered Dose inhaler (MDI)
Dry powder inhaler (DPI)
Soft mist inhaler
Nebulizer

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22
Q

What are the advantages to using a metered dose inhaler?

A

Small, compact, portable
Easy to use
Can be used with spacer
No drug prep

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23
Q

What are the disadvantages to using a metered dose inhaler?

A

Needs proper technique/coordination of breath
Contains propellants
Expensive

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24
Q

What are the advantages of using a dry powder inhaler?

A

Small, compact, portable
Easy to use
Usually cheaper than an MDI
No coordination needed

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25
Q

What are the disadvantages of using dry powder inhaler?

A

Patient must prep the dose
Requires fast, deep inhalation
Moisture sensitive
NOT IDEAL FOR COPD patients

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26
Q

What are the different types of dry powder inhalers?

A 
Diskus
Handihaler
Twisthaler
Ellipta
Pressair
Flexhaler
Aerolizer
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27
Q

What are the advantages of using a soft mist inhaler?

A

Compact, portable
Multi-dose device
High lung deposition
Does not contain propellants

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28
Q

What are the disadvantages of using a soft mist inhaler?

A

Complicated process for the first dose
Slow moving mist
Cannot use a spacer
Expensive

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29
Q

What are the advantages of using a nebulizer?

A

Minimal technique required

Patient is not required to hold breath

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30
Q

What are the disadvantages of using a nebulizer?

A 
Expensive
Requires dose prep
Bulky
Administration time is 5-15 minutes
Needs a power source
Cleaning needed
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31
Q

What are the bronchodilators?

A 
SABA
LABA
Muscarinic antagonists
Methylxanthine derivatives
PDE-4 inhibitors
32
Q

What do we want the medications to do in order to prevent bronchoconstriction and increase bronchodilation?

A

Bronchoconstriction = inhibit ACh and adenosine

Bronchodilation = increase cAMP levels or prevent cAMP from being broken down

33
Q

What is the MOA of SABAs and LABAs?

A

Stimulates adenylyl cyclase at beta 2 receptor to increase cAMP in bronchial smooth muscle –>

BRONCHODILATION

34
Q

What are SABAs the drug of choice for?

A

Acute asthma attacks and exercise induced asthma

35
Q

What is the onset and duration of SABAs?

A 
Onset = 5 min.
Duration = 3-4 hours
36
Q

What is the administration of SABAs?

A

inhalation

37
Q

What are the ADRs of SABAs and LABAs?

A

Mouth irritation
Cough

At high doses:
Skeletal muscle tremor
Tachycardia/Palpitations
Arrhythmias
Tolerance with excessive use
38
Q

What is the onset and duration of LABAs?

A 
Onset = 30 min.
Duration = 12-24 hours
39
Q

What are LABAs used for?

A

CANNOT BE USED in MONOTHERAPY for asthma

THEY MUST BE USED WITH A CORTICOSTEROID for asthma treatment

Not for rescue therapy

Can be used in monotherapy for COPD

40
Q

What is the MOA of antimuscarinic agents?

A

Competitively block muscarinic receptors and the effects of ACh in the airway which prevents vasoconstriction mediated by vagal discharge

41
Q

What effects do antimuscarinic agents have and what are they typically used to treat?

A

no effects on chronic inflammation

mostly used in COPD

42
Q

What are the ADRs of antimuscarinic agents?

A

minimally absorbed and generally well tolerated

Potential for:
Dry mouth/eyes
Bitter, metallic taste
Constipation
Urinary retention
43
Q

What is the MOA of Methylxanthine derivatives?

A
  1. Nonselevtively inhibits PDE to increase cAMP causing BRONCHODILATION
  2. Blocks adenosine receptors in CNS
44
Q

What is the duration of action for methylxanthine derivatives?

A

12 hours

45
Q

What are methylxanthine derivatives used for?

A

PO in IR and SR forms

Requires high concentrations to be efffective

Considered Narrow Therapeutic index drug so they are not used very often to treat asthma/COPD

46
Q

What is Theophylline metabolized by and what are it’s DDIs?

A

CYP450 1A2

Febuxostat
Bupropion
Cabamazepine
Macrolide antibiotics

47
Q

What is the clearance of theophylline mediated by?

A

Age
Smoking status
Other drugs

Younger patients clear drug faster
Smokers clear the drug faster

48
Q

What monitoring is required with theophylline use?

A

Therapeutic monitoring for range between 10-20 mcg/mL

49
Q

What are the ADRs of theophylline?

A

GI DISTRESS (enhanced gastric acid secretion)
Tremor
Insomnia
In overdose = severe nausea and vomitting, hypotension, agitation, arrythmias, cardiac arrest, and seizures

50
Q

What is the MOA of PDE-4 inhibitors?

A

Selectively inhibits PDE-4 to increase cAMP causing Bronchodilation

51
Q

What are PDE-4 inhibitors used for?

A

Severe or very severe COPD

Should be given in combo with at least 1 other long acting bronchodilator for COPD

52
Q

What DDI’s are there with Roflumilast?

A

CYP450 3A4

Rifampin
Phenobarbital
Phenytoin
Carbamazepine

53
Q

What are the ADRs of Roflumilast?

A 
Diarrhea/N/V
Abdominal pain
headache
Dyspepsia
Psychiatric events
Weight loss
54
Q

What is the MOA of corticosteroids?

A

Binds to glucocorticoid receptors to:

Inhibit inflammatory cell migration and activation

Inhibit cytokine and mediator release

UPregulate beta 2 receptors

Inhibit IgE synthesis

55
Q

What are corticosteroids used for?

A

Persistent asthma

56
Q

Which corticosteroid is safest to use in pregnancy?

A

Budesonide

57
Q

What are the ADRs of inhaled corticosteroids?

A

Thrush = counsel patients to wash mouth after each use
Dysphonia
Sore throat
Cough

58
Q

What are the ADRs of oral corticosteroids?

A 
Adrenal suppression
Cushing syndrome
Growth retardation
Osteoporosis
Glucose intolerance
Infection risk
Mood changes
Weight gain
Edema
59
Q

What are leukotrienes?

A

Inflammatory mediators derived from arachadonic acids

60
Q

What do leukotrienes do?

A

Produce bronchoconstriction
Recruit eosinophils
Vascular and mucus secretions

61
Q

What is the MOA of Lipoxygenase inhibitors?

A

Inhibits actions of 5-lipoxygenase to inhibit the synthesis of leukotrienes

62
Q

What are the ADRs of lipoxygenase inhibitors?

A 
Headache
Insomnia
Somnolence
GI upset
HEPATOTOXICITY = do not use if LFTs are greater than 3X the upper limit of normal; do not give to female patients older than 65 and patients with preexisting LFT elevations
63
Q

What is the MOA of leukotriene receptor antagonists?

A

competitively blocks actions of leukotrienes at the LTD4 receptor

64
Q

What are leukotriene receptor antagonists used for?

A

Asthma
Allergic symptoms
Exercise-induced bronchospasm
Urticaria

Adjunctive treatment

65
Q

Which leukotriene receptor antagonist has a DDI with warfarin?

A

Zafirlukast increased risk of bleed

66
Q

What are the ADRs of leukotriene receptor antagonists?

A

Headache

Hepatotoxicity = Zafirlukast

67
Q

Which leukotriene receptor antagonist has a BBW for neuropsychiatric events and what events are they?

A

Montolukast

Abnormal dreams
Hostility
Aggression
Suicidality
Agitation
Hallucinations
68
Q

What is the MOA of Mast cell stabilizers?

A

Block influx of Ca to prevent mast cell degranulation which stablizes the mast cell and prevents release of inflammatory mediators

NO direct bronchodilating, antihistaminic or anti-inflammatory effects

69
Q

What are mast cell stabilizers used to treat?

A

mild asthma

Not used often in practice

70
Q

What are the ADRs of mast cell stabilizers?

A 
Mild throat irritation
Cough
Abnormal taste in mouth
Requires multiple daily doses
takes 2-6 weeks to take full effect
71
Q

What is the MOA of Omalizumab?

A

Inhibits binding of IgE to surface of mast cells and basophils which inhibits release of inflammatory medaitors

72
Q

What is Omalizumab used to treat?

A

Allergic asthma not relieved with corticosteroid treatment = patient must have allergy testing done prior to use

73
Q

What is the dose of Omalizumab based on?

A

IgE levels and body weight

74
Q

What are the ADRs of Omalizumab?

A 
Don't use in patients under the age of 12
Takes 12 weeks to work
Injection site reactions
Anaphylaxis 1.5-2 hours after dose
Arthralgia
Headache
Pharyngitis
Sinusitis
Malignancies
75
Q

What is the MOA of IL-5 antagonists?

A

Humanized interleukin-5 monoclonal antibody antagonist to reduce the amount of circulating eosinophils

76
Q

What are IL-5 antagonists used to treat?

A

Used for maintenance of severe asthma for patient who continues to have exacerbation despite adequate therapy

CAN ONLY BE USED in patients who are 18 or older that have eosinophil

77
Q

What are the ADRs of IL-5 antagonists?

A 
Not recommended for monotherapy
Injection site reactions
Headache
Hypersensitivity reactions
Malignancy
Muscle and face pain

Clinical Pharmacology II (25 decks)

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