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Therapuetics - Exam 3 > Lecture 22/23 > Flashcards

Lecture 22/23 Flashcards

drugs used in asthma

1
Q

extrinsic asthma

A

hypersensitivity reaction induced by exposure to an extrinsic antigen
commonly associated with other allergies and genetics
onset is early in life
elevated serum IgE levels and eosinophil count
driven by TH2 subset of CD4+ T cells
two types: acute and sustained

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2
Q

acute bronchoconstriction

A

immediate response within 30 to 60 mins after antigen inhalation
occurs after sensitization, mediated by IgE

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3
Q

acute asthma pathway

A

mast cell degranulation –> release of histamine, tryptase, leukotrienes, and PGD2 –> smooth muscle contraction and vascular leakage –> direct stimulation of subepithelial vagal receptors –> reflex bronchoconstriction

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4
Q

sustained bronchoconstriction

A

late asthmatic response 3 to 6 hours after the immediate response
caused by the activation of TH2 cells and cytokine production and activation of eosinophils

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5
Q

sustained asthma pathway

A

activation of TH2 cells and cytokine production –> activation of eosinophils –> release MBP, ECP, peroxidase –> tissue damage –> amplify and sustain inflammation

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6
Q

intrinsic asthma

A

nonimmune triggering mechanism
example - aspirin, viral infection, cold, physiological stress, and exercise
no personal or family history of allergy
serum IgE levels are normal

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7
Q

IgE in acute

A

produced in response to foreign proteins
mediates sensitization
binds to FceR-1 on mast cells

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8
Q

mast cells in acute

A

in airway mucosa
release histamine, tryptase, leukotrienes, and PGD2

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9
Q

vagal (parasympathetic) receptors

A

direct stimulate provokes reflex bronchoconstriction in acute asthma

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10
Q

sympathomimetics

A

bronchodilators
types - nonselective, B selective, B2 selective
increases the cAMP concentration –> relaxation of muscle cells

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11
Q

nonselective sympathomimetic

A

example - epinephrine
IV injection to relieve a severe attack

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12
Q

B selective sympathomimetic

A

example - isoproterenol
displaced therapeutically by B2 selective drugs
affects the heart

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13
Q

B2 selective sympathomimetic

A

SABA and LABA drugs
most used for asthma treatment
SAR - bulky N-substitutions = B2 selective; phenyl ring substitutions = B2 selective and resistant to COMT

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14
Q

inhaled corticosteroids (ICSs)

A

anti-inflammatory steroids (controllers)
effective only so long as they are taken
systemic or oral are reserved for severe cases
most effective way to minimize adverse effects

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15
Q

leukotriene pathway inhibitors

A

either 5-lipoxygenase inhibitor or LTD4 antagonists
improve asthma control and reduce the frequency of asthma exacerbations
not as effective as IGC

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16
Q

5-lipoxygenase inhibitor

A

example - zileuton
alternative to LABA in addition to ICS
not for acute asthma
blocks LTB4 (a potent neutrophil chemoattract)
requires liver monitoring

17
Q

LTD4 antagonists

A

also know as selective antagonists for the cysLT1 receptor
examples - Zafirlukast, Montelukast
blocks the binding of LTC4, LTD4, and LTE4 to the receptor
once a day dosing with good bioavailability

18
Q

methylxanthine

A

examples - theophylline, theobromine, and caffeine
still used in some countries due to low cost (replaced by B2 selective agonists)

19
Q

methylxanthine mechanism

A

inhibit phosphodiesterase –> increase cAMP concentration –> block adenosine –> suppress histamine release and increase bronchodilation

20
Q

antimuscarinic agents

A

inhibit the action of acetylcholine at muscarinic receptors to prevent constriction and mucus secretion
used in pts intolerant of inhaled B agonists
example - ipratropium

21
Q

ipratropium

A

bronchodilator
type of antimuscarinic agent
derivative of atropine
poorly absorbed in the circulation after inhaled due to minimal oral bioavailability

22
Q

mast cell stabilizers

A

examples - cromolyn, nedocromil
inhibit mast cell degranulation
contraindication with direct bronchodilator actions
alternative use - allergic rhinoconjunctivitis as eye drops

23
Q

monoclonal antibodies

A

target either IgE or IL5
examples - omalizumab, mepolizumab, reslizumab, benralizumab

24
Q

omalizumab

A

inhibits IgE binding to mast cells
reserved for patients with severe asthma and allergic sensitization

25
Q

mepolizumab, reslizumab, bentralizumab

A

anti-IL5 monoclonal abs
maintenance therapy of severe asthma in patients with eosinophilic phenotype
prevents the release of TH2 cells that attract and activate eosinophils

26
Q

SABA

A

short acting b2 agonists
examples - albuterol, terbutaline, metaproterenol, pirbuterol
used - prn for acute attacks

27
Q

albuterol

A

most widely used
resistant to COMT due to salicyl alcohol in phenyl ring
5min onset with 4-8 hour duration when inhaled

28
Q

terbutaline

A

greater b2 selectivity with 3 fold greater potency than metaproterenol
good oral bioavailability

29
Q

metaproterenol

A

somewhat selective for b2 receptor
least potent b2 agonist
5min onset with 4 hour duration when inhaled

30
Q

pributerol

A

analogous to albuterol except for pyridine ring
comparable duration of action to albuterol, but with less potency

31
Q

LABA

A

long acting b2 agonists
examples - salmeterol, formoterol, and in-combo with ICSs
uses - additional therapy for patients who is currently using IGCs; daily regular use

32
Q

salmeterol

A

available as powder
LABA
greater lipid solubility due to dissolve in cellular membranes
20 min onset with 12 hour duration of action

33
Q

formoterol

A

LABA
available as powder
more rapid onset than salmeterol with a comparable duration
resistant to COMT and MAO

34
Q

LABA does NOT

A

treat acute attacks
have inflammatory action
have usage in monotherapies

35
Q

ICSs

A

triamcinolone acetonide
beclomethasone dipropionate
budesonide
mometasone furoate
fluticasone propionate
ciclesonide

Therapuetics - Exam 3 (12 decks)

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