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PHA 550 > Asthma > Flashcards

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
Q

Asthma: Step 5

A

high dose ICS + LABA and consider omalizumab for patients who have allergies

consult with asthma specialist

26
Q

Asthma: Step 6

A

high dose ICS + LABA + oral corticosteroids and consider omalizumab for patients who have allergies

consult with asthma specialist

27
Q

What is the therapy target in the arachidonic cascade?

A

LTD4 (leukotriene)

28
Q

Effects of Nitric Acid in Asthma

A 
smooth muscle relaxation
capillary leakage
increased mucus secretion
inflammatory cell chemotaxis (eosinophils, T lymphocytes)(iNOS)
remodeling (arginase pathway)
29
Q

Muscarinic Effects (dumbbbelss)

A 
diarrhea
urination
miosis/muscle weakness
bronchorrhea
bronchospasm
bradycardia
emesis
lacrimation
salivation
sweating
30
Q

Beta 2 Agonist: MOA

A

beta adrenoreceptor agonist

stimulate adenylyl cyclase–> inc cAMP in smooth muscle–> powerful bronchodilator response

31
Q

Beta 2 Agonist: agents, method of delivery

A

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
Q

Beta 2 Agonist: albuterol (SABA)

A

beta selective bronchodilation

acute asthma attacks

ADE: toxicities, tachycardia

33
Q

Beta 2 Agonist: salmeterol (LABA)

A

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
Q

Antimuscarinic (Anticholinergic) Agents

A

atropine: belladonna alkaloid
ipratropium: little systemic action
tiotropium: longer acting analog

35
Q

Antimuscarinics: MOA

A

competitively block muscarinic receptors –> prevent bronchoconstriction

can also reverse bronchoconstriction in asthmatic children and COPD patients

36
Q

Antimuscarinics: ipratropium, tiotropium

A

competitive muscarinic antagonists

asthma and COPD

ADE: dry mouth, cough

37
Q

Methylxanthines

A

provide stimulant effects

caffeine (coffee)(inc CNS effect)
theophylline (tea)
theobromine (cocoa)(inc cardiac effect)

38
Q

Theophylline: MOA

A
  • inhibits PDE –> inc cAMP
  • blocks adenosine receptors

**adenosine: can momentarily stop the electrical impulse propagation through the heart, esp for PSVT

39
Q

Theophylline

A

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
Q

Theophylline: clearance

A

highest in young adolescents

higher in smokers

varies with concurrent use of other drugs that inhibit/induce hepatic enzymes

41
Q

Theophylline: clinical applications, effects, ADEs

A

asthma (prophylactic against nocturnal attacks)

bronchodilation
cardiac stimulation
inc skeletal muscle strength

ADE: 
insomnia
tremor
anorexia
seizures
arrhythmias
42
Q

Theophylline: dosage

A

start low
go slow
check drug levels

43
Q

Corticosteroids: prednisone, prednisolone

A

systemic (oral)

acute exacerbations
or
chronically when other tx unsuccessful

44
Q

Corticosteroids: beclomethasone, budesonide, dexamethasone, flunisolide, fluticasone, mometasone

A

aerosol

common 1st line for mod-sev asthma

45
Q

Corticosteroids: prednisolone and hydrocortisone

A

IV

for status asthmaticus

46
Q

Corticosteroid: MOA

A
  • 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
Q

Inhaled Corticosteroids: clinical applications, ADEs

A

prophylaxis if asthma (drugs of choice)

ADEs:
pharyngeal candidiasis
minimal systemic steroid toxicity (eg: adrenal suppression)

48
Q

Systemic Corticosteroids: clinical applications

A

treatment of severe refractory chronic asthma

49
Q

Inhaled Corticosteroids: beneficial effects

A

dec eosinophils

dec mast cells

dec T lymphocyte cytokine production

inhibition of transcription of inflammatory genes in airway epithelium

reduced endothelial cell leak

50
Q

Inhaled Corticosteroids: beneficial effects

A

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
Q

Inhaled Corticosteroids: potential adverse effects

A

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
Q

Look at systemic corticosteroid comparison chart slide 44

A

dexamethasone might be the best but idk

53
Q

Are ICS medications routinely prescribed or written for PRN use?

A

Routinely prescribed - they’re late phase

54
Q

Leukotriene Antagonists: MOA

A

interfere with the synthesis/action of leukotrienes

not as effective as corticosteroids in severe asthma

55
Q

Leukotriene Antagonists: zafirlukast, montelukast

A

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
Q

Leukotriene Antagonists: zileuton

A

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
Q

Aspirin Allergy

A

bronchospasm resulting from ingestion of aspirin

divert all eicosanoid production to leukotrienes when cyclooxygenase pathway is blocked

58
Q

Leukotriene Antagonists: clinical application

A

prophylaxis of asthma

59
Q

Cromolyn and Nedocromil

A

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
Q

Cromolyn: MOA

A

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
Q

Monoclonal Antibodies: Omalizumab

A

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
Q

Monoclonal Antibody: Mepolizumab, Benralizumab, Reslizumab

A

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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