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

LECTURES 22 & 23 - drugs used in asthma Flashcards

(51 cards)

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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

Study These Flashcards
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

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

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

Study These Flashcards
A

epinephrine (IV for severe attack)

24
Q

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

Study These Flashcards
A

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

25
List drug(s) in the beta-selective sympathomimetic category
Isoproterenol
26
List drug(s) in the B2-selective sympathomimetic category - specifically LABAs
Salmeterol (Serevent®) Formoterol (Foradil®) Arformoterol (Brovana®)
27
Explain the mechanism of action of leukotriene pathway inhibitors
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
List 5-Lipoxygenase Inhibitor drug(s) used for treatment of asthma
Zileuton (Zyflo®)
29
List Cysteinyl Leukotriene Receptor Antagonists (LTRAs) used for treatment of asthma
Zafirlukast (Accolate®) Montelukast (Singulair®)
30
List Inhaled Corticosteroids (ICSs) used for treatment of asthma
Triamcinolone acetonide (Azmacort®) Beclomethasone dipropionate (__, __) Flunisolide (Aerobid®) Budesonide (Pulmicort®) Mometasone furoate (Asmanex®) Fluticasone propionate (Flovent®) Ciclesonide (Alvesco®)
31
Describe the mechanism of action of methylxanthines (phosphodiesterase inhibitors)
- 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
List methylxanthines (phosphodiesterase inhibitors) used to treat asthma
Theophylline (most effective) Theobromine Caffeine
33
Describe the mechanism of action of antimuscarinic agents (anticholinergics)
- Stimulation of cholinergic (parasympathetic) nerves causes bronchoconstriction and mucus secretion - Antimuscarinic drugs competitively inhibit the action of acetylcholine at muscarinic receptors
34
List antimuscarinic agents (anticholinergics) used to treat asthma
Ipratropium (Atrovent®)
35
Describe the mechanism of action of mast cell stabilizers
Inhibit mast cell degradation (no direct bronchodilator action)
36
List mast cell stabilizers used to treat asthma
Cromolyn (Gastrocrom®, Intal®) Nedocromil (Tilade®)
37
Describe the mechanism of action of monoclonal antibodies (biologics)
- 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
List the anti-IgE biologic(s) used to treat asthma
Omalizumab (Xolair®)
39
List the anti-IL5 biologic(s) used to treat asthma
Reslizumab (Cinqair®) Mepolizumab (Nucala®)
40
List the anti-IL5 reeptor biologic(s) used to treat asthma
Benralizumab (Fasenra®)
41
List the anti-IL4 receptor biologic(s) used to treat asthma
Dupilumab (Dupixent®)
42
List the anti-TSLP (thymic stromal lymphopoietin) biologic(s) used to treat asthma
Tezepelumab (Tezspire®)
43
Describe Metaproterenol (Alupent)
--SABA-- - Resorcinol analogue of isoproterenol - Least potent B-2 agonist - When inhaled → 5-min onset, 4-hour duration - Good oral bioavailability
44
Describe Terbutaline (Brethine)
-- SABA -- - N-t-butyl analogue of metaproterenol - More selective for B-2 - 3-fold greater potency than metaproterenol - Good oral bioavailability
45
Describe Albuterol (Ventolin)
-- 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
Describe Pirbuterol (Maxair)
- Analogous to albuterol, but has a pyridine ring - Comparable duration of action to albuterol - Less potent than albuterol
47
Describe LABAs
CONTRAINDICATED as monotherapy - Usually used in combination with inhaled corticosteroids (ICSs) - Not for acute attacks
48
Describe Salmeterol (Serevent)
-- LABA -- - Greater water solubility - Moderate lipophilicity - 20-min onset & 12-hour DOA - Moderate resistance to MAO/COMT - Available as a powder
49
Describe Formoterol (Foradil)
-- LABA -- - Highest receptor affinity - Comparable DOA to salmeterol - More rapid onset than salmeterol - Increased lipophilicity & resistance to MAO/COMT
50
List inhaled corticosteroids used as a maintenance therapy for asthma
- Triamcinolone acetonide - Beclomethasone dipropionate - Budesonide - Flunisolide - Mometasone furoate - Fluticasone propionate - Ciclesonide
51
List the monoclonal antibodies used in asthma
Omalizumab (Xolair®) Reslizumab (Cinqair®) Mepolizumab (Nucala®) Benralizumab (Fasenra®) Dupilumab (Dupixent®) Tezepelumab (Tezspire®)

PHRM 825 - Exam 3 (8 decks)

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