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PHRM 5001 > 4. Non-Steroidal Anti-Asthma Medications > Flashcards

4. Non-Steroidal Anti-Asthma Medications Flashcards

1
Q

Non-steroidal anti-asthma agents are used in the prophylactic management of what type of asthma?
When is it indicated? (in relation to use of rescue drug)

A

mild, persistent asthma (controller/maintenance, introduced for “poor control”)

indicated if rescue drugs needed > 2x/week

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2
Q

List some general indications.

A

alternative to low-dose inhaled corticosteroids, infants/young children, combined with ICS to low dose of steroid

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3
Q

Inflammation manifests as:

A

broncho-constriction, a/w swelling, mucus secretion, a/w obstruction, a/w remodeling

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4
Q

What are the 3 categories of agents?

A

mast cell stabilizers, anti-leukotrienes, monoclonal antibodies

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5
Q

How do mast cell stabilizers prevent degranulation?

A

controlling the releasing inflammatory mediators: histamine, chemotactic factors, eicosanoid mediators (LoX, CoX) (leukotrienes, prostaglandins, thromboxane)

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6
Q 
Cromolyn (Intal):
Prevents influx of \_\_\_ into mast cells. 
Target cells can or cannot degranulate? 
Suppresses the release what? 
Inhibits what class of mediators?
Age range?
How long for full prophylactic effect?
Effect is dependent on what?
A

Ca +2
target cells CANNOT degranulate
suppresses release of arachidonic acid from nuclear membrane phospholipids
inhibits the eicosanoid class of mediators
> or equal to 2 years
6-12 weeks
dose

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7
Q

What are the available formulations of Cromolyn (Intal)? (Hint: 6)

A

nebulized solution, MDI, DPI, Nasal solution, Eye drops, Oral

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8
Q

What are the contraindications of Cromolyn? Precautions?

A

acute exacerbations, hypersensitivity

systemic corticosteroids must be tapered, patients exhibiting poor compliance, not to be mixed with iptratropium

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9
Q

Adverse reactions to Cromolyn? (Hint: 5)

A

throat irritation/hoarseness with DPI, nasal congestion, urticaria, dizziness, headaches

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10
Q

Ketotifen (Zaditen):

what type of effects? antagonizes what? Formulations? How long for full prophylaxis?

A

anti-allergic/anti-histaminic
antagonizes histamine at H1 histamine receptors (sustained action)
oral pill/syrup
1-2 months

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11
Q

Nedocromil (Tilade):

mechanism of action? Formulations? Age range?

A

arachidonic acid pathway suppression: suppresses HRF, blocks release of adhesion molecules (ICAM-I), blocks neuropeptide synthesis (substance P)
MDI
> 12 yo

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12
Q

What are the 2 different mechanisms of action for antileukotrienes?

A
  1. antagonist drugs that compete for LT receptors (blocking agents)
  2. inhibitor drugs that prevent the synthesis of leukotrienes
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13
Q

What are leukotrienes products of?

A

arachidonic acid metabolism via the lipoxygenase pathway

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14
Q

AA is found in the nuclear membranes of:

A

mast cells, granulocytes, macrophages/monocytes, B lymphocytes

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15
Q

Stimulation of leukotrienes induces:

A

broncho-constriction, capillary leakage, vasodilation, increased glandular secretions, leukocyte chemotaxis

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16
Q

What are the 2 different leukotriene receptors? What is the result when stimulated?

A

BLT - stimulation by LTB4 results in chemotaxis of WBCs (neutrophils/eosinophils)
CysLT - stimulation by cysteinyl luekotrienes (LTC4, LTD4, LTE4) causes potent histamine-like effects (*CysLT1 found in a/w, CysLT2 found in pulmonary vessels)

17
Q 
Zafirlukast (Accolate):
Antagonizes which receptor/leukotrienes? Reduces severity of inflammation induced by: (Hint 4)
Dose?
Age range?
Precautions/Interactions?
A

antagonist at CysLT1 receptor
competitively antagonizes LTC4, LTD4, LTE4
exercise, cold air, allergens, aspirin
oral prep BID, 1-2 hr after meal
12+ years (5+ in US)
pre-existing liver dysfunction, increased serum theophylline levels, increased clotting times in pts on warfarin, inhibits aspirin

18
Q

Adverse effects of Zafirlukast (Accolate)

A

headache, infection, nausea, liver enzyme changes

19
Q 
Montelukast (Singulaire):
Blocks what receptor?
Age range?
Administration?
Drug interactions?
Adverse Effects?
A 
Competitively antagonizes CysLT1
2+ (6 months+ in US)
oral prep (tablets, chewables, granules) taken +/- food in evening
no reported drug interactions
headache, influenza, abdominal pain
20
Q 
Zileuton (Zyflo):
Inhibits what?
Administration?
Age range?
Contraindications?
Drug interactions?
Adverse effects?
A

inhibits 5-lipoxygenase (suppresses chemoattraction/spasmogen in a/w
oral agent
12 +
pts with active liver disease/elevated liver enzymes
theophylline, warfarin, propranolol
headache, pain, liver enzyme elevations, dyspepsia

21
Q

List some advantages of leukotriene modifiers.

A

generally well tolerated, may have higher compliance due to oral option vs. inhaled, symptoms improvement may be greater in more severe asthmatics, can have additive effects with ICS

22
Q

List some disadvantages of leukotriene modifiers.

A

elevation of serum hepatic enzyme, side effects: headache, GI disturbances, nausea, vomiting, rashes, fever, and has some drug interactions

23
Q

Define monoclonal.

A

identical clones of a single parent immune cell

24
Q

Antigen is used to generate ____ _____

A

specific mAbs

25
Q

What do B lymphocytes do in response to an allergen/antigen? How are the B lymphocytes stimulated?

A

produce IgE

overreacting T cell sends out IL3/4

26
Q

In the a/w how is IgE prevented from attaching to target cells? What are these target cells?

A

mAbs bind to IgE

mast cells, basophils, a/w smooth muscle cells

27
Q

How are mAbs produced?

A
  1. immunization of mouse (Ag challenge)
  2. isolation of B lymphocytes from the spleen
  3. cultivation of myeloma cells
  4. myeloma cells + B cells = hybridomas
  5. separation of cells lines
  6. mAbs screened for Ag specificity
  7. selected hybridoma cells maintained in continuous cell culture to grow (unlimited Ab production)
  8. screened for antibodies
28
Q

What are mAbs designed to do?

A

suppress immune system, kill/inhibit malignant cells, inhibit angiogenesis

29
Q 
Omalizumab (Xolair):
Type?
Circulating complexes with IgE inhibit what?
Indications?
Administration?
How long till peak concentration?
Adverse effects?
A

Anti-IgE mAb
binding to the IgE receptors on target cells
control of severe asthma
subq injection every 2-4 weeks depending on pt weight/serum IgE level
peak after 7-8 days
anaphylaxis, malignancies, injection site reactions, viral infection, URTI, pharyngitis

PHRM 5001 (12 decks)

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