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PHRM 825 - Exam 3 > LECTURES 22 & 23 - drugs used in asthma > Flashcards

LECTURES 22 & 23 - drugs used in asthma Flashcards

1
Q

describe extrinsic asthma

A
  • allergic or “classical” asthma
  • hypersensitivity reaction induced by exposure to an extrinsic antigen
    (ex. dust mite, molds, pollens)
  • commonly associated with other allergy in the past in the patient as well in other family members
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2
Q

what is the onset of extrinsic asthma?

A

usually early in life

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3
Q

describe the immune response in extrinsic asthma

A
  • elevated serum IgE levels & eosinophil count
  • driven by TH-2 subset of CD4+ T-cells
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4
Q

describe intrinsic asthma

A

nonimmune triggering mechanism
(ex. aspirin, viral infection, cold, psychological stress, exercise)
-> no personal or family hx of allergy

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5
Q

List the main events in the acute bronchoconstriction

A

– mediated by IgE –

  1. IgE binds to FcεR-1 on mast cells in the airway mucosa
  2. Re-exposure to the allergen trigger the release of mediators from the mast cells
    (Mast cell degranulation)
  3. Mast cells release histamine, tryptase, PGD-2, leukotrienes (LTC-2, LTD-4)
    (Mediators cause smooth muscle contraction and vascular leakage)
  4. Direct stimulation of subepithelial vagal (parasympathetic) receptors provokes reflex bronchoconstriction
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6
Q

describe serum IgE levels in intrinsic asthma

A

Serum IgE levels are normal

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7
Q

List the main events in the sustained bronchoconstriction

A

– Caused by the activation of TH-2 cells and cytokine production (IL-5, IL-9, IL-13) –

  1. Attract & activate eosinophils
    – Releases major basic proteins (MBP), eosinophil cationic protein (ECP), peroxidase
    (Causes tissue damage)
    – Amplifies and sustains the inflammation without additional exposure to the triggering antigen
  2. Stimulate mucus hypersecretion by bronchial epithelial cells
  3. Stimulate IgE production by B lymphocytes
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8
Q

What does IAR stand for?

A

immediate asthmatic response

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9
Q

What does LAR stand for?

A

late asthmatic response

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10
Q

What does FEV-1 stand for?

A

forced expiratory volume

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11
Q

What does ECP stand for?

A

eosinophil cationic protein

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12
Q

What does PAF stand for?

A

platelet activiating factor

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13
Q

Describe neutrophil proteases

A

may activate eosinophils

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14
Q

Describe periostin

A

matrix protein that is used as an asthma biomarker

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15
Q

describe FEV-1

A

used to meaure efficacy of asthma therapy

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16
Q

describe ECP

A

cytotoxic secretory protein & marker of inflammation

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17
Q

Describe PAF

A

causes hyperresponsiveness

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18
Q

Explain the role of IgE in the pathology of extrinsic asthma

A
  • IgE is bound to FcεR-1 on mast cells
  • Cross-linking by the antigen leads to mast-cell degradation
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19
Q

Explain the role of mast cells in the pathology of extrinsic asthma

A

mast cell degranulation leads to the release of granule contents

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20
Q

Explain the role of vagal (parasympathetic) receptors in bronchoconstriction

A

When the receptors are directly stimulated, they provoke reflex bronchoconstriction
– acute bronchoconstriction (IAR) –

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21
Q

Explain the mechanism of action of sympathomimetics

A

Binds to B-2 adrenergic receptors in the bronchial smooth muscle

Increases the cAMP concentration → relaxes the muscle cells

22
Q

List the types of sympathomimetics used to treat asthma

A
  • non-selective
  • beta selective
  • B-2 selective (SABAs, LABAs)
23
Q

List drug(s) in the non-selective sympathomimetic category

A

epinephrine (IV for severe attack)

24
Q

List drug(s) in the B2-selective sympathomimetic category - specifically SABAs

A

Albuterol (Ventolin®)
Levalbuterol (Xopenex®)
Metaproterenol (Alupent®)
Terbutaline (Brethine®)
Pirbuterol (Maxair®)

25
Q

List drug(s) in the beta-selective sympathomimetic category

A

Isoproterenol

26
Q

List drug(s) in the B2-selective sympathomimetic category - specifically LABAs

A

Salmeterol (Serevent®)
Formoterol (Foradil®)
Arformoterol (Brovana®)

27
Q

Explain the mechanism of action of leukotriene pathway inhibitors

A

5-Lipoxygenase Inhibitor –> inhibits 5-lipooxygenase

Cysteinyl Leukotriene Receptor Antagonists (LTRAs) –> Blocks the binding of LTC-4, LTD-4, and LTE-4 to the receptor

28
Q

List 5-Lipoxygenase Inhibitor drug(s) used for treatment of asthma

A

Zileuton (Zyflo®)

29
Q

List Cysteinyl Leukotriene Receptor Antagonists (LTRAs) used for treatment of asthma

A

Zafirlukast (Accolate®)
Montelukast (Singulair®)

30
Q

List Inhaled Corticosteroids (ICSs) used for treatment of asthma

A

Triamcinolone acetonide (Azmacort®)
Beclomethasone dipropionate (__, __)
Flunisolide (Aerobid®)
Budesonide (Pulmicort®)
Mometasone furoate (Asmanex®)
Fluticasone propionate (Flovent®)
Ciclesonide (Alvesco®)

31
Q

Describe the mechanism of action of methylxanthines (phosphodiesterase inhibitors)

A
  • Inhibition of phosphodiesterase (PDE-3 and PDE-4) increase in the cellular cAMP concentration
    – Bronchodilation and suppression of histamine release
  • Block the action of adenosine, which causes bronchoconstriction and the release of histamine
  • Histone deacetylation, which suppresses inflammatory gene expression
32
Q

List methylxanthines (phosphodiesterase inhibitors) used to treat asthma

A

Theophylline (most effective)
Theobromine
Caffeine

33
Q

Describe the mechanism of action of antimuscarinic agents (anticholinergics)

A
  • Stimulation of cholinergic (parasympathetic) nerves causes bronchoconstriction and mucus secretion
  • Antimuscarinic drugs competitively inhibit the action of acetylcholine at muscarinic receptors
34
Q

List antimuscarinic agents (anticholinergics) used to treat asthma

A

Ipratropium (Atrovent®)

35
Q

Describe the mechanism of action of mast cell stabilizers

A

Inhibit mast cell degradation
(no direct bronchodilator action)

36
Q

List mast cell stabilizers used to treat asthma

A

Cromolyn (Gastrocrom®, Intal®)
Nedocromil (Tilade®)

37
Q

Describe the mechanism of action of monoclonal antibodies (biologics)

A
  • Recognizes the portion of IgE that binds to its receptor (FcεR-1 and FcεR-2) on immune cells
  • Inhibits IgE binding to mast cells
38
Q

List the anti-IgE biologic(s) used to treat asthma

A

Omalizumab (Xolair®)

39
Q

List the anti-IL5 biologic(s) used to treat asthma

A

Reslizumab (Cinqair®)
Mepolizumab (Nucala®)

40
Q

List the anti-IL5 reeptor biologic(s) used to treat asthma

A

Benralizumab (Fasenra®)

41
Q

List the anti-IL4 receptor biologic(s) used to treat asthma

A

Dupilumab (Dupixent®)

42
Q

List the anti-TSLP (thymic stromal lymphopoietin) biologic(s) used to treat asthma

A

Tezepelumab (Tezspire®)

43
Q

Describe Metaproterenol (Alupent)

A

–SABA–

  • Resorcinol analogue of isoproterenol
  • Least potent B-2 agonist
  • When inhaled → 5-min onset, 4-hour duration
  • Good oral bioavailability
44
Q

Describe Terbutaline (Brethine)

A

– SABA –

  • N-t-butyl analogue of metaproterenol
  • More selective for B-2
  • 3-fold greater potency than metaproterenol
  • Good oral bioavailability
45
Q

Describe Albuterol (Ventolin)

A

– SABA –

  • MOST WIDELY USED
  • Resistant to COMT → salicyl alcohol in the phenyl ring
  • When inhaled → 5-min onset & 4-8 hour duration
  • Levalbuterol → used when albuterol has side effects in pediatric patients
  • R-isomer of albuterol
  • Greater potency, but more expensive
46
Q

Describe Pirbuterol (Maxair)

A
  • Analogous to albuterol, but has a pyridine ring
  • Comparable duration of action to albuterol
  • Less potent than albuterol
47
Q

Describe LABAs

A

CONTRAINDICATED as monotherapy

  • Usually used in combination with inhaled corticosteroids (ICSs)
  • Not for acute attacks
48
Q

Describe Salmeterol (Serevent)

A

– LABA –

  • Greater water solubility
  • Moderate lipophilicity
  • 20-min onset & 12-hour DOA
  • Moderate resistance to MAO/COMT
  • Available as a powder
49
Q

Describe Formoterol (Foradil)

A

– LABA –

  • Highest receptor affinity
  • Comparable DOA to salmeterol
  • More rapid onset than salmeterol
  • Increased lipophilicity & resistance to MAO/COMT
50
Q

List inhaled corticosteroids used as a maintenance therapy for asthma

A
  • Triamcinolone acetonide
  • Beclomethasone dipropionate
  • Budesonide
  • Flunisolide
  • Mometasone furoate
  • Fluticasone propionate
  • Ciclesonide
51
Q

List the monoclonal antibodies used in asthma

A

Omalizumab (Xolair®)
Reslizumab (Cinqair®)
Mepolizumab (Nucala®)
Benralizumab (Fasenra®)
Dupilumab (Dupixent®)
Tezepelumab (Tezspire®)

PHRM 825 - Exam 3 (8 decks)

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