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Asthma Flashcards

1
Q

Drugs that trigger or increase susceptibility to asthma

A 
acetaminophen
aspirin
NSAIDs (cyclooxygenase inhibitors)
sulfites
benzalkonium chloride
nonselective beta blockers
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2
Q

Asthma

A

reversible airflow obstruction

prolonged expiration

diffuse wheezes

sx worse at night/early morning

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3
Q

Asthma: targets of drug therapy

A
  • narrow airway
  • tightened muscles
  • inflammation
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4
Q

Asthma: diagnostics

A

limitation of airflow on PFTs
or
positive bronchoprovocation challenge

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5
Q

Asthma: pathology

A

bronchial lumen is narrowed due to:
-airway remodeling (hypertrophy of BM, mucus plugging, hypertrophy of smooth muscle, hypertrophic goblet cells)

-inflammation (infiltration of inflammatory cells, edema, cellular debris)

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6
Q

Phases of Asthma: immediate asthmatic response

A

minutes

bronchoconstriction

lymphocytes and mast cells
histamine and prostaglandins

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7
Q

Phases of Asthma: late asthmatic response

A

hours

submucosal edema, hyperresponsiveness

neutrophils, macrophages, eosinophils, monocytes

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8
Q

Phases of Asthma: chronic asthma

A

days

epithelial damage, mucus hypersecretion, hyperresponsiveness

eosinophils, lymphocytes
preeosinophil

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9
Q

Asthma and Exercise

A

initial bronchodilation then crash in PEF

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10
Q

Intermittent Asthma (initial)

A 
symptoms: = 2 d/wk
nighttime awakenings: = 2 d/wk
SABA use: =2 d/wk
limit on activity: none
FEV1: >80%
FEV1/FVC: >85% or N
exacerbation risk: 0-1/year
recommended step: step 1
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11
Q

Persistent Mild Asthma (initial)

A 
symptoms: >2d/wk
nighttime awakenings: 3-4/mo
SABA use: >2d/wk
limit on activity: minor
FEV1: >80%
FEV1/FVC: >80% or N
exacerbation risk: >/= 2/yr
recommended step: step 2
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12
Q

Persistent Moderate Asthma (initial)

A 
symptoms: daily
nighttime awakenings: >1x/week
SABA use: daily
limit on activity: some
FEV1: 60-80%
FEV1/FVC: 75-80%
exacerbation risk: >/=2/year
recommended step: step 3
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13
Q

Persistent Severe Asthma (initial)

A 
symptoms: throughout the day
nighttime awakenings: 7x/wk
SABA use: several times per day
limit on activity: extreme
FEV1: <60%
FEV1/FVC: <75%
exacerbation risk: >/=2/year
recommended step: step 3/4
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14
Q

Risk Factors for Exacerbations

A

uncontrolled asthma symptoms
high SABA use
>/= 1 exacerbation in the last 12 months
low FEV1
incorrect inhaler technique/poor adherence
smoking
obesity, chronic rhinosinusitis, pregnancy, blood eosinophilia

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15
Q

Risk factors for fixed airflow limitation

A 
no ICS treatment
smoking
occupational exposures
mucus hyper secretion
blood eosinophilia
pre term birth
low birth weight
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16
Q

Risk factors for medication side effects

A

frequent oral steroids
high dose ICS
P450 inhibitors

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17
Q

Treatment Goals

A

prevent bronchoconstriction
reduce inflammation
prevent irritant reaction

immunotherapy if severe

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18
Q

Treatment Goals: prevent bronchoconstriction (agents)

A

early phase - rescue

  • beta 2 agonist
  • theophylline
  • anticholinergic (antimuscarinic)
  • mediator antagonist
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19
Q

Treatment Goals: reduce inflammation (agents)

A

late/chronic phase - controller

-corticosteroids

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20
Q

Treatment Goals: prevent irritant reaction (IgE) (agents)

A

aka bronchial hyperresponsiveness

late/chronic phase

  • lipoxygenase
  • leukotriene inhibitors
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21
Q

Asthma: Step 1

A

SABA as needed

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22
Q

Asthma: Step 2

A

low dose ICS

alternative: cromolyn, LTRA, theophylline

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23
Q

Asthma: Step 3

A

low dose ICS + LABA
or
medium dose ICS

alternative: low dose ICS + either LTRA, theophylline, zileuton

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24
Q

Asthma: Step 4

A

medium dose ICS + LABA

alternative: medium dose ICS+either LTRA, theoyphylline, zileuton

consult with asthma specialist

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25
Asthma: Step 5
high dose ICS + LABA and consider omalizumab for patients who have allergies consult with asthma specialist
26
Asthma: Step 6
high dose ICS + LABA + oral corticosteroids and consider omalizumab for patients who have allergies consult with asthma specialist
27
What is the therapy target in the arachidonic cascade?
LTD4 (leukotriene)
28
Effects of Nitric Acid in Asthma
``` smooth muscle relaxation capillary leakage increased mucus secretion inflammatory cell chemotaxis (eosinophils, T lymphocytes)(iNOS) remodeling (arginase pathway) ```
29
Muscarinic Effects (dumbbbelss)
``` diarrhea urination miosis/muscle weakness bronchorrhea bronchospasm bradycardia emesis lacrimation salivation sweating ```
30
Beta 2 Agonist: MOA
beta adrenoreceptor agonist stimulate adenylyl cyclase--> inc cAMP in smooth muscle--> powerful bronchodilator response
31
Beta 2 Agonist: agents, method of delivery
albuterol, terbutaline, metaproterenol (~6 hr duration) salmeterol, formoterol, indacaterol (12-24hr duration) inhalation - dec systemic dose (adverse effects) - effective dose to airway smooth muscle
32
Beta 2 Agonist: albuterol (SABA)
beta selective bronchodilation acute asthma attacks ADE: toxicities, tachycardia
33
Beta 2 Agonist: salmeterol (LABA)
beta 2 selective bronchodilation, potentiation of corticosteroid action asthma prophylaxis (NOT acute release) slow onset preventative potentiates corticosteroid effects ADE: tremor, tachycardia, cardiovascular events
34
Antimuscarinic (Anticholinergic) Agents
atropine: belladonna alkaloid ipratropium: little systemic action tiotropium: longer acting analog
35
Antimuscarinics: MOA
competitively block muscarinic receptors --> prevent bronchoconstriction can also reverse bronchoconstriction in asthmatic children and COPD patients
36
Antimuscarinics: ipratropium, tiotropium
competitive muscarinic antagonists asthma and COPD ADE: dry mouth, cough
37
Methylxanthines
provide stimulant effects caffeine (coffee)(inc CNS effect) theophylline (tea) theobromine (cocoa)(inc cardiac effect)
38
Theophylline: MOA
- inhibits PDE --> inc cAMP - blocks adenosine receptors **adenosine: can momentarily stop the electrical impulse propagation through the heart, esp for PSVT
39
Theophylline
bronchodilation inc strength of contraction of the diaphragm CNS stimulation, cardiac stimulation, vasodilation, inc BP, diuresis, inc GI motility **beta blockers are useful in reversing severe cardiovascular toxicity from theophylline. elimination through liver CYP450 enzymes
40
Theophylline: clearance
highest in young adolescents higher in smokers varies with concurrent use of other drugs that inhibit/induce hepatic enzymes
41
Theophylline: clinical applications, effects, ADEs
asthma (prophylactic against nocturnal attacks) bronchodilation cardiac stimulation inc skeletal muscle strength ``` ADE: insomnia tremor anorexia seizures arrhythmias ```
42
Theophylline: dosage
start low go slow check drug levels
43
Corticosteroids: prednisone, prednisolone
systemic (oral) acute exacerbations or chronically when other tx unsuccessful
44
Corticosteroids: beclomethasone, budesonide, dexamethasone, flunisolide, fluticasone, mometasone
aerosol common 1st line for mod-sev asthma
45
Corticosteroids: prednisolone and hydrocortisone
IV for status asthmaticus
46
Corticosteroid: MOA
- reduce synthesis of arachidonic acid by phospholipase A2 - inhibit/red expression of COX-2 (inducible form of cyclooxygenase) inc responsiveness of beta adrenoreceptors reduces mediators of inflammation
47
Inhaled Corticosteroids: clinical applications, ADEs
prophylaxis if asthma (drugs of choice) ADEs: pharyngeal candidiasis minimal systemic steroid toxicity (eg: adrenal suppression)
48
Systemic Corticosteroids: clinical applications
treatment of severe refractory chronic asthma
49
Inhaled Corticosteroids: beneficial effects
dec eosinophils dec mast cells dec T lymphocyte cytokine production inhibition of transcription of inflammatory genes in airway epithelium reduced endothelial cell leak
50
Inhaled Corticosteroids: beneficial effects
dec eosinophils dec mast cells dec T lymphocyte cytokine production inhibition of transcription of inflammatory genes in airway epithelium reduced endothelial cell leak upregulates beta 2 receptor production reduced airway epithelial subbasement membrane thickening
51
Inhaled Corticosteroids: potential adverse effects
hoarseness, dysphonia, thrush growth retardation, skeletal muscle myopathy osteoporosis, fractures, aseptic necrosis of hip posterior subcapsular cataract formation and glaucoma adrenal axis suppression, immunosuppression impaired wound healing, easy bruising, striae hyperglycemia/hypokalemia, HTN psychiatric disturbances
52
Look at systemic corticosteroid comparison chart slide 44
dexamethasone might be the best but idk
53
Are ICS medications routinely prescribed or written for PRN use?
Routinely prescribed - they're late phase
54
Leukotriene Antagonists: MOA
interfere with the synthesis/action of leukotrienes not as effective as corticosteroids in severe asthma
55
Leukotriene Antagonists: zafirlukast, montelukast
leukotriene receptor blockers - antagonists at LTD 4 receptor prevent exercise, antigen, aspirin induced bronchospasm NOT recommended for acute episodes designed to be most useful for nighttime symptoms
56
Leukotriene Antagonists: zileuton
selectively inhibits 5-lipoxygenase (converts arachidonic acid to leukotrienes) prevents exercise and antigen induced bronchospasm effective against "aspirin allergy" ADE: elevation of liver enzymes
57
Aspirin Allergy
bronchospasm resulting from ingestion of aspirin divert all eicosanoid production to leukotrienes when cyclooxygenase pathway is blocked
58
Leukotriene Antagonists: clinical application
prophylaxis of asthma
59
Cromolyn and Nedocromil
anti IgE antibody rarely used in the US use prior to gardening or outdoor activity prophylaxis of asthma (also ophthalmic, nasopharyngeal, GI allergy) ADE: cough
60
Cromolyn: MOA
dec in the release of mediators (leukotrienes, histamines) from mast cells prevents bronchoconstriction/ acute bronchospasm prevent early and late response to challenge some efficacy preventing food allergy
61
Monoclonal Antibodies: Omalizumab
anti-IgE antibody binds to IgE on mast cell --> prevents activation by asthma triggers and inflammatory mediator release prophylactic for severe, refractory asthma reduces frequency of exacerbations parenteral long term toxicity
62
Monoclonal Antibody: Mepolizumab, Benralizumab, Reslizumab
antibody to IL-5 severe eosinophilic asthma 12+ years old frequent exacerbations **marker for eos phenotype: : absolute eos count in peripheral blood >/=150 enables a reduction in the oral glucocorticoid dose SQ **sm inc in herpes zoster in treated adults (vaccine at least 4 wks prior to initiation)

PHA 550 (26 decks)

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