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Pharm I ( Melicia) > Asthma > Flashcards

Asthma Flashcards

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
Q

LABA MOA?

A

beta2 selective agonists, bronchodilation, potentiation of corticosteroid action

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26
Q

Salmeterol clinical application?

A

asthma prophylaxis

Indacaterol for COPD

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27
Q

effects of Salmeterol?

A

slow onset, primarily preventative action, potentiates corticosteroid effects

28
Q

Salmeterol toxicities?

A

tremor, tachycardia, CV events

29
Q

What are some antimuscarinic (anticholinergic) agents?

A

Atropine

Ipratropium

Tiotropium: longer acting analogue of Ipratropium

30
Q

Ipatropium and Tiotropium MOA?

A

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
Q

Do antimuscarinic agents have an effect on the chronic inflammatory aspects of asthma?

A

NO

32
Q

Toxicities of Ipratropium and Tiotropium?

A

dry mouth, cough

33
Q

What are three major Methylxatines, which are found in plants and provide the stimulant effect of 3 common drinks?

A

Caffeine

Theophylline (tea)

Theobromine (cocoa)

34
Q

Theophylline MOA?

A

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
Q

Effects of theophylline?

A

Bronchodilation

Increased strength of contraction of diaphragm

Other effects: CNS stimulation, cardiac stimulation, vasodilation, slight increased in BP, diuresis, increased GI motility

36
Q

What can be used to revere severe CV toxicity from theophylline?

A

Beta blockers

37
Q

Theophylline PK?

A

oral

short and long acting formulations

eliminated through liver CYP450 enzymes

clearance varies w/ age: highest in young adults, higher in smokers

38
Q

Clinical applications of theophylline?

A

asthma, especially prophylactic against nocturnal attacks

39
Q

Theophylline toxicities?

A

insomnia, tremor, anorexia, seizures, arrhythmias

40
Q

How should you dose Theophylline?

A

gradually increase as tolerated

41
Q

Name some corticosteroids

A

Prednisone, Beclomethasome, Budesonide, Fluticasone, Mometasone

all potentially beneficially in severe asthma

42
Q

When are systemic corticosteroids used?

A

for acute exacerbations or chronically only when other therapies are unsuccessful

43
Q

Prednisolone is an…

A

active metabolite of prednisone

important IV corticosteroids for status asthmaticus

44
Q

Corticosteroid MOA?

A

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
Q

Effects of inhaled corticosteroids like Beclomethasone?

A

Reduces mediators of inflammation, powerful prophylaxis of exacerbations

46
Q

Beclomethasone toxicities?

A

pharyngeal candidiasis

minimal systemic steroid toxicity (such as adrenal suppression).

47
Q

What are some of the beneficial effects of inhaled corticosteroids?

A

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
Q

What are some potential adverse effects of inhaled corticosteroids?

A

hoarseness, dysphonia, thrush, growth retardation, skeletal muscle myopathy, osteoporosis, fractures, adrenal axis suppression, immunosuppression, impaired wound healing, HTN, psychiatric disturbances

49
Q

Use of ICS in children…

A

does cause mild growth retardation

but these children will generally reach full predicted adult stature

50
Q

Which systemic corticosteroid has the high anti-inflammatory potency?

A

dexamethasone

51
Q

Leukotriene antagonists MOA?

A

interfere with the synthesis or the action of the leukotrienes

-not as effective as corticosteroids in severe asthma

52
Q

Name 2 leukotriene antagonists (receptor blockers)

A

Zafirlukast and Montelukast

-antagonists at the LTD4 leukotriene receptor

orally active

53
Q

Clinical application of Montelukast?

A

effective in preventing exercise, antigen and aspirin induced bronchospasm

-not recommended for acute episodes of asthma-

54
Q

Name a lipoxygenase inhibitor (Leukotriene antagonist). MOA?

A

Zileuton

orally active drug

selectively inhibits 5 lipoxygenase, which is a key enzyme in the conversion of arachidonic acid to leukotrienes

55
Q

Zileuton clinical application?

A

prevents both exercise and antigen induced bronchospasm, affective against “ASA allergy”

56
Q

Zileuton toxicities?

A

elevation in liver enzymes

57
Q

When is cromolyn used?

A

rarely in US, use prior to gardening or outdoor activity

Anti-igE antiiody

58
Q

Cromolyn MOA?

A

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
Q

Cromolyn can also be used for…

A

ophthalmic, nassopharyngeal and GI allergy

60
Q

Side effect of Cromolyn?

A

cough

61
Q

What are some monoclonal abs for use in asthma?

A

omalizumab, mepolizumab, benralizumab

62
Q

Omalizumab drug class? MOA?

A

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
Q

Why is Omalizumab not really used?

A

very expensive and must be administered parenterally

64
Q

What pts can Mepolizumab be used in?

A

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
Q

GINA asthma dx…pt must have?

A

-hx of respiratory sxs that vary over time and intensity

  • variable expiratory airflow limitation
  • reduced FEV1/FVC
  • FEV1 increases >12% w/ bronchodilator tx
66
Q

GINA recommends what to asthma pts, even though with infrequent sxs, to reduce the risk of serious exacerbations?

A

ICS

67
Q

Asthma step wise tx approach, what do you give at each step?

A 
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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