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Pharm I ( Melicia) > Asthma > Flashcards

Asthma Flashcards

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1
Q

What is bronchial hyper reactivity?

A

Pathologic increase in the bronchoconstrictor response to antigens and irritants; caused by bronchial inflammation

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2
Q

What is an IgE mediated disease?

A

Disease caused by excessive or misdirected immune response mediated by IgE antibodies.

Example: asthma

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3
Q

What is mast cell degranulation?

A

exocytosis of granules from mast cells with release of mediators of inflammation and bronchoconstriciton

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4
Q

What is phosphodiesterase (PDE)?

A

family of enzymes that degrade cyclic nucleotides to nucleotides

ex. cAMP (active) to AMP (inactive)

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5
Q

What is tachyphylaxis?

A

rapid loss of responsiveness to a stimulus

i.e. a drug

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6
Q

What are some agents/events that can trigger or increase susceptibility to asthma?

A

Respiratory infection, Allergens Environment (cold air, nitrogen dioxide, tobacco smoke, etc.), emotions, exercise, drugs/preservatives (Acetaminophen, ASA, NSAIDs, sulfites), occupation stimuli

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7
Q

Host factors that increase the risk for asthma…

A

obesity, African American race, Hispanic ethnicity, low SES

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8
Q

What are some high sulfite containing foods that may trigger asthma?

A

dried fruit, lemon juice, wine, molasses

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9
Q

Describe asthma

A

episodic or chronic sxs of airflow obstruction

reversibility of airflow obstruction spontaneous or after bronchodilator

prolonged expiratory and diffuse wheezes on PE

limitation of airflow on PFT or + bronchoprovocation challenge

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10
Q

What is asthma drug therapy aimed at?

A

narrow airway, tightened muscles, inflammation

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11
Q

Pathology found in asthmatic bronchus?

A

narrowed lumen:

hypertrophy of the BM, mucus plugging and smooth muscle hypertrophy and constriction contribute

inflammatory cells infiltrate, producing submucosal edema & epithelial desquamation fills airway w/ cellular debris and exposes airway to smooth muscles to other mediators

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12
Q

What are the different phases of asthma?

A

Immediate asthma response (IAR): minutes –> bronchoconstriction

late asthma response (LAR): hours–> submucosal edema, hyper-responsiveness

chronic asthma: epithelial cell damage, mucus hyper secretion, hyper-responsiveness

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13
Q

What are the long term goals of asthma management?

A
  • achieve good control of sxs and maintain norm. activity levels
  • minimize future risk of exacerbations, fixed airflow limitation and side effects

(According to GINA-global initiative for asthma)

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14
Q

Asthma treatment goals in immediate phase? (rescue)

A

Prevent bronchoconstriction (rescue)

  • B2 adrenergic agonist
  • theophylline
  • anticholinergic (antimuscarinic)
  • Mediator antagonist
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15
Q

Asthma treatment goals in late/chronic phase? (controller)

A

reduce inflammation
-corticosteroids

prevent irritant reaction (IgE)
(bronchial hyper-responsiveness)
-lipoxygenase or leukotriene inhibitors

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16
Q

B agonists, muscarinic antagonists, theophylline and leukotriene antagonists all work to…

A

alter bronchial tone in asthma

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17
Q

Beta agonists MOA?

A

stimulate adenylyl cyclase

increase cyclic adenosine monophosphate (cAMP) in smooth muscle cells

increase in cAMP results in a powerful bronchodilator response

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18
Q

Name 3 Beta2 agonists

A

Albuterol*
Terbutaline
Metaproterenol

(inhalation route decreases the systemic dose & adverse effects while delivering an effective dose locally to the airway smooth muscle)

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19
Q

Duration of action of newer beta2 agonist agents such as salmeterol, formoterol and indacaterol? older agents?

A

12-24hrs

older agents: 6 hrs or less

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20
Q

Clinical application of Albuterol?

A

acute asthma attack drug of choice

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21
Q

Effects of albuterol?

A

prompt bronchodilation

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22
Q

Albuterol toxicities?

A

tremor, tachycardia

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23
Q

Which short acting beta2 agonists can be given orally or parenterally?

A

Terbutaline

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24
Q

Name 3 long acting beta agonists

A

Salmeterol, formoterol, indacaterol

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25
LABA MOA?
beta2 selective agonists, bronchodilation, potentiation of corticosteroid action
26
Salmeterol clinical application?
asthma prophylaxis Indacaterol for COPD
27
effects of Salmeterol?
slow onset, primarily preventative action, potentiates corticosteroid effects
28
Salmeterol toxicities?
tremor, tachycardia, CV events
29
What are some antimuscarinic (anticholinergic) agents?
Atropine Ipratropium Tiotropium: longer acting analogue of Ipratropium
30
Ipatropium and Tiotropium MOA?
given as aerosol competitively block muscarinic receptors in the airways and effectively prevent bronchoconstriction mediated by vagal discharge reverse bronchoconstriction in some asthma pts and in many pts with COPD
31
Do antimuscarinic agents have an effect on the chronic inflammatory aspects of asthma?
NO
32
Toxicities of Ipratropium and Tiotropium?
dry mouth, cough
33
What are three major Methylxatines, which are found in plants and provide the stimulant effect of 3 common drinks?
Caffeine Theophylline (tea) Theobromine (cocoa)
34
Theophylline MOA?
inhibits phosphodiesterase (PDE) -enzyme that degrades cAMP to AMP, thus increase cAMP block adenosine receptors (adenosine as used to momentarily stop electrical impulse propagation through the heart)
35
Effects of theophylline?
Bronchodilation Increased strength of contraction of diaphragm Other effects: CNS stimulation, cardiac stimulation, vasodilation, slight increased in BP, diuresis, increased GI motility
36
What can be used to revere severe CV toxicity from theophylline?
Beta blockers
37
Theophylline PK?
oral short and long acting formulations eliminated through liver CYP450 enzymes clearance varies w/ age: highest in young adults, higher in smokers
38
Clinical applications of theophylline?
asthma, especially prophylactic against nocturnal attacks
39
Theophylline toxicities?
insomnia, tremor, anorexia, seizures, arrhythmias
40
How should you dose Theophylline?
gradually increase as tolerated
41
Name some corticosteroids
Prednisone, Beclomethasome, Budesonide, Fluticasone, Mometasone all potentially beneficially in severe asthma
42
When are systemic corticosteroids used?
for acute exacerbations or chronically only when other therapies are unsuccessful
43
Prednisolone is an...
active metabolite of prednisone important IV corticosteroids for status asthmaticus
44
Corticosteroid MOA?
reduce the synthesis of arachidonic acid by phospholipase A2 and inhibit the expression of COX-2, the inducible form of cyclooxygenase increase the responsiveness of beta in the airway prevent the full expression of inflammation and allergy by activating glucocorticoid response elements reduce activity of phospholipase A
45
Effects of inhaled corticosteroids like Beclomethasone?
Reduces mediators of inflammation, powerful prophylaxis of exacerbations
46
Beclomethasone toxicities?
pharyngeal candidiasis minimal systemic steroid toxicity (such as adrenal suppression).
47
What are some of the beneficial effects of inhaled corticosteroids?
decreased eosinophils/mast cells/t lymphocyte cytokine production inhibit transcription of inflammatory genes in airway epithelium reduce epithelial cell leak upregulate B2 receptor production reduce airway thickening
48
What are some potential adverse effects of inhaled corticosteroids?
hoarseness, dysphonia, thrush, growth retardation, skeletal muscle myopathy, osteoporosis, fractures, adrenal axis suppression, immunosuppression, impaired wound healing, HTN, psychiatric disturbances
49
Use of ICS in children...
does cause mild growth retardation but these children will generally reach full predicted adult stature
50
Which systemic corticosteroid has the high anti-inflammatory potency?
dexamethasone
51
Leukotriene antagonists MOA?
interfere with the synthesis or the action of the leukotrienes -not as effective as corticosteroids in severe asthma
52
Name 2 leukotriene antagonists (receptor blockers)
Zafirlukast and Montelukast -antagonists at the LTD4 leukotriene receptor orally active
53
Clinical application of Montelukast?
effective in preventing exercise, antigen and aspirin induced bronchospasm -not recommended for acute episodes of asthma-
54
Name a lipoxygenase inhibitor (Leukotriene antagonist). MOA?
Zileuton orally active drug selectively inhibits 5 lipoxygenase, which is a key enzyme in the conversion of arachidonic acid to leukotrienes
55
Zileuton clinical application?
prevents both exercise and antigen induced bronchospasm, affective against "ASA allergy"
56
Zileuton toxicities?
elevation in liver enzymes
57
When is cromolyn used?
rarely in US, use prior to gardening or outdoor activity Anti-igE antiiody
58
Cromolyn MOA?
poorly understood. decreased in release of mediators (leukotrienes), can prevent bronchoconstriction, prevent early and late responses to challenge. Cromolyn can help w/ preventing food allergy.
59
Cromolyn can also be used for...
ophthalmic, nassopharyngeal and GI allergy
60
Side effect of Cromolyn?
cough
61
What are some monoclonal abs for use in asthma?
omalizumab, mepolizumab, benralizumab
62
Omalizumab drug class? MOA?
anti IgE antibody humanized murune monoclonal ab to human IgE binds to the igE on sensitized mast cells and prevents activation by asthma triggers and subsequent release of inflammatory mediators
63
Why is Omalizumab not really used?
very expensive and must be administered parenterally
64
What pts can Mepolizumab be used in?
tx of asthma in pts who are age 12 or older, have freq. asthma exacerbations and have an eosinophilic phenotype (one marker eosinophil count >150) admin SQ at 4 wk intervals small increase in herpes zoster in treated adults
65
GINA asthma dx...pt must have?
-hx of respiratory sxs that vary over time and intensity - variable expiratory airflow limitation - reduced FEV1/FVC - FEV1 increases >12% w/ bronchodilator tx
66
GINA recommends what to asthma pts, even though with infrequent sxs, to reduce the risk of serious exacerbations?
ICS
67
Asthma step wise tx approach, what do you give at each step?
``` 1- maybe ICS 2-low dose IC 3- low dose ICS/LABA 4-med or high ICS/LABA 5-refer for add on tx ``` SABA for all

Pharm I ( Melicia) (18 decks)

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