Anti-Inflammatory and
Anti-asthmatic Agents
MODULE F
Objectives
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List two mast cell stabilizers.
Describe and diagram the antigen/antibody
reaction on mast cells
Explain which antibody is elevated in allergic
asthma.
List three mediators that are released with
inflammation.
Explain the effects of chemical mediators such as
histamine and leukotrienes on airway epithelium.
Objectives
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Given signs and symptoms, differentiate between
the early and late phase of an inflammatory
response.
Describe how cromolyn sodium and nedocromil
are anti-inflammatory agents.
State the generic and trade names, modes of
action, adverse reactions, routes of
administration, dosages, and adverse reactions
for cromolyn sodium and nedocromil sodium.
State the origin of corticosteroid secretion.
Describe why corticosteroids are now considered
first line drugs in the treatment of asthma.
Describe the pathway for the release and control
of corticosteroids in the body.
Objectives
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Define HPA insufficiency.
Differentiate between systemic and inhaled
corticosteroids.
List three actions of steroids on inflammation.
Describe the process of weaning a patient from
steroids.
List four side effects or adverse reactions of
steroid administration.
State the trade and generic names of the inhaled
steroids discussed in class.
Objectives
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Describe how a RCP can decrease the incidence
of oral fungal infections when administering
aerosolized steroids.
List three leukotrienes inhibitors discussed in
class.
State two side effects of leukotrienes.
State how leukotrienes are administered.
Describe the cellular mechanism for leukotriene
production.
State three medication types that are used for
upper-airway congestion.
State the IgE inhibitor used to treat asthma.
Anti-Inflammatory Drugs
• Non-Steroidal Anti-inflammatory
• Mast Cell Stabilizers or anti-asthmatics
• Leukotriene Antagonists (antileukotrienes)
• Adrenocorticosteroid Antiinflammatory
• Corticosteroids or Steroids
Mechanism of Inflammation
• Mast Cells, eosinophils, macrophages,
basophils are found in submucosa.
• The cells contain granules that are
storehouses of the chemical mediators of
lung inflammation.
• Antigen-Antibody reactions causes the
influx of Ca+2 into the cells and release of
mediators.
• IgE primary antibody
Mechanism of Inflammation
• Mediator Release
• Bronchospasm
• Vasodilation resulting in mucosal edema
• Increased vascular permeability
• Increased mucus gland secretion
Mediators of Inflammation
• Histamine
• Platelet Activating Factor
• Eosinophil Chemotactic Factor of Anaphylaxis
(ECF-A)
• Neutrophil Chemotactic Factor of Anaphylaxis
(NCF-A)
• Leukotrienes (formerly known as slow-reacting
substance of anaphylaxis – SRS-A)
• Prostaglandins
• Explanation of Mast
Cell rupture
(Degranulation)
• Figure 7-1, p. 132
• Mast cells are found
throughout the body
and their sensitization
explains the watery
eyes, runny nose, etc.
that accompanies an
allergic reaction.
Phases of Inflammatory
Response in Asthma
• Early phase - Immediate
• Late phase – 6 to 8 hours after exposure
Early Phase
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Local vasodilation
Increased vascular permeability
Redness
Bronchoconstriction
Wheezing
Coughing
Dyspnea
Hypoxemia
Late Phase
• Effect of WBC (lymphocyte) and other
mediators
• Hypersecretion of mucus and mucosal
swelling
• Traffic Jam
• Breakdown of Mast Cell releases
Arachidonic Acid
• Production of leukotrienes
• Prostaglandin
FIGURE 7-2, page 134
Goal of Therapy
• Stop Mast Cell from degranulating
• Prophylactic Anti-asthmatics
• Stop specific inflammatory processes
• Corticosteroids
• Broad spectrum response
• Leukotriene Inhibitors
• Antihistamines
• Prostaglandin Inhibitors
Mast Cell Stabilizers
• Prevent Ca+2 influx into the cell, thereby
preventing mediator release.
• cromolyn sodium
• Intal, Nasalcrom
• nedocromil sodium
• Tilade
• Ketotifen (Experimental)
• Zaditen
• These medications do not operate through the
C’AMP system and do not stimulate b or a
receptor sites
• Best used in limited populations and mild asthma
Indications for Mast Cell
Stabilizers
• Prophylactic management of Asthma.
• Pre-treatment for expected exposure.
• Prevention of exercise induced asthma
• Allergic rhinitis
• Do not use to treat an asthmatic attack
cromolyn sodium (1973)
• Small Volume Nebulizer
• Concentration: 1%
• Supplied in a 2 mL ampule (unit dose)
containing 20 mg (20 mg/2 mL).
• Give one ampule QID; may need to add
additional diluent (2 mL may nebulize too
quickly).
• MDI:
• 0.8 mg/inhalation
• 2 inhalations QID
• Ophthalmic and Nasal solutions available
Hazards/Adverse Reactions
• Generally well tolerated
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Nasal congestion
Throat irritation
Hoarseness
Dry mouth
Cough
Feeling of chest tightness
Wheezing/Sneezing/Epistaxis
• Give b2 agonist prior to administering Cromolyn
nedocromil sodium (1992)
• Tilade
• MDI:
• 1.75 mg/inhalation
• 2 inhalations QID
• Side Effects similar to cromolyn
Adrenocorticosteroids
• Secreted from the adrenal cortex.
• Epinephrine secreted from adrenal medulla.
• Multiple functions of medication.
• Anti-inflammatory.
• Orally, parenterally, aerosol.
• First line drugs in the management of
asthma.
• Reliever and controller medication.
• Given to control allergies.
Adrenal Gland
ADRENAL
CORTEX
HPA Axis
• Hypothalamic Pituitary Adrenal Axis
• Low blood levels of steroids.
• Hypothalamus is stimulated.
• Sends impulse to Anterior Pituitary Gland
which stimulates Corticotropin Releasing
Factor (CRF).
• This stimulates the formation of
Adrenocorticotropin hormone (ACTH ).
• ACTH in bloodstream stimulates Adrenal
Cortex to produce and release Corticosteroids.
• Increases blood levels of corticosteroids.
FIGURE 7-3, page 137
HPA Axis
• Diurnal or Circadian Rhythm
• Levels are highest around 8:00 a.m.
• Off-shift workers.
• Giving a patient steroids can suppress the
body’s HPA axis (Body stops producing
steroids).
• If you stop the added steroids abruptly, the
patient will experience HPA insufficiency
and death can occur.
HPA Insufficiency
• Once adrenal suppression has occurred,
the patient must be weaned slowly from
systemic steroids.
• This will allow for recovery of the body’s
own secretion.
• HPA insufficiency begins 1 day after use of
systemic steroid administration.
Prevention of HPA
Insufficiency
• Low dose steroid for 5 days or less.
• Take steroids in the morning when natural
levels are high.
• High dose tapered regimen lasting 5-6
days.
• Alternate day therapy.
Buffalo
Hump &
Moon Face
FIGURE 7-5, page 139
Cushing's Syndrome
• Increased secretion of corticosteroids
caused by a tumor of the adrenal glands
• Cushingoid appearance
• Central obesity
• Moon face
• Buffalo hump
Aerosolized Steroids
• Advantage is that aerosolized steroids do
not increase the blood levels of steroids
• Does not cause HPA insufficiency
• Less side effects
• Goal is to try to gain control of asthma with
the aerosolized steroids
• May take 4-8 weeks for maximum
improvement
Oral vs. Aerosol Corticosteroids
Common Inhaled Steroids
Page 140
Adverse Reactions of
Aerosolized Steroids
• Fungal Infections may occur after aerosol
• Rinse mouth and use spacer
• Throat irritation, hoarseness, dry mouth
and coughing have occurred
• HPA insufficiency may occur during transfer
from systemic to aerosol steroids
• Severe asthma may occur following
withdrawal of oral/IV steroids
Adverse
Reactions/Precautions
• Aerosolized steroids may not be adequate
to control asthma during periods of stress
and systemic administration may be
necessary
Leukotriene Modifiers
Anti-Leukotrienes
Leukotriene Antagonists
Leukotriene Inhibitors
Leukotriene Inhibitors
• Indications
• Prophylactic treatment of asthma
• “Controllers”
• Not to be used to treat an asthma attack
• zileuton
• Zyflo
• zafirlukast
• Accolate
• montelukast
• Singulair
Leukotriene Inhibitors
• zileuton (Zyflo)
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12 years of age or older
Works well in aspirin-sensitive asthmatics
600 mg orally QID
Elevate liver enzymes
Interaction with
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Warfarin
Seldane
Theophylline
Propanolol
• 5 - Lipoxygenase inhibitor
Leukotriene Inhibitors
• zafirlukast (Accolate)
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12 years of age or older
10 or 20 mg orally BID
Elevates liver enzymes
Interactions
• Warfarin
• Theophylline
• Blocks the leukotriene receptor site
(leukotriene receptor antagonist)
Leukotriene Inhibitors
• montelukast (Singular)
• Daily dosing
• 4 mg packet of granules (6 to 23 months )
• 4 mg chewable tablet or 4 mg packet of granules (2
to 5 years of age)
• 5 mg chewable tablet (child)
• 10 mg tablet (adult)
• Side effects: headache, influenza, abdominal
pain
• Blocks the leukotriene receptor site
(Leukotriene receptor antagonist)
Disadvantage of Antileukotrienes
• Inhibit one mediator pathway
• Asthma involves multiple mediators
• 50 – 70% of patients respond to the
medication
• Trial & Error
Upper Airway Congestion
• Allergic Rhinitis
• Antihistamine
• Prevents release of histamine.
• Significant side effects
• Newer generation are more “forgiving”
• Intranasal Medications
• Mast Cell Stabilizers (Nasalcrom)
• Nasal Steroids
• Decongestants
• a-adrenergic agents
• Vasoconstriction
• Table 7-14 (page 140)
ciclesonide
Omnaris
IGE Inhibitors
• omalizumab (Xolair)
Dosing
• http://www.xolair.com/hcp/dosing_calculato
r2.jsp