Anti-Inflammatory Drugs by wuyunqing


									Anti-Inflammatory and
Anti-asthmatic Agents
      MODULE F
•   List two mast cell stabilizers.
•   Describe and diagram the antigen/antibody
    reaction on mast cells
•   Explain which antibody is elevated in allergic
•   List three mediators that are released with
•   Explain the effects of chemical mediators such as
    histamine and leukotrienes on airway epithelium.
•   Given signs and symptoms, differentiate between
    the early and late phase of an inflammatory
•   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.
•   Define HPA insufficiency.
•   Differentiate between systemic and inhaled
•   List three actions of steroids on inflammation.
•   Describe the process of weaning a patient from
•   List four side effects or adverse reactions of
    steroid administration.
•   State the trade and generic names of the inhaled
    steroids discussed in class.
•   Describe how a RCP can decrease the incidence
    of oral fungal infections when administering
    aerosolized steroids.
•   List three leukotrienes inhibitors discussed in
•   State two side effects of leukotrienes.
•   State how leukotrienes are administered.
•   Describe the cellular mechanism for leukotriene
•   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 (anti-
• Adrenocorticosteroid Anti-
  • 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
  • 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
• Neutrophil Chemotactic Factor of Anaphylaxis
• Leukotrienes (formerly known as slow-reacting
  substance of anaphylaxis – SRS-A)
• Prostaglandins
• Explanation of Mast
  Cell rupture
• 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
•   Local vasodilation
•   Increased vascular permeability
•   Redness
•   Bronchoconstriction
•   Wheezing
•   Coughing
•   Dyspnea
•   Hypoxemia
                  Late Phase
• Effect of WBC (lymphocyte) and other
• Hypersecretion of mucus and mucosal
  • 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

• 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
• MDI:
  • 0.8 mg/inhalation
  • 2 inhalations QID
• Ophthalmic and Nasal solutions available
      Hazards/Adverse Reactions
• Generally well tolerated
  •   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
• 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
  • Reliever and controller medication.
• Given to control allergies.
Adrenal Gland

                  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
• 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
• 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
• Alternate day therapy.
                       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
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
• Aerosolized steroids may not be adequate
  to control asthma during periods of stress
  and systemic administration may be
 Leukotriene Modifiers
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)
  •   12 years of age or older
  •   Works well in aspirin-sensitive asthmatics
  •   600 mg orally QID
  •   Elevate liver enzymes
  •   Interaction with
       •   Warfarin
       •   Seldane
       •   Theophylline
       •   Propanolol
  • 5 - Lipoxygenase inhibitor
           Leukotriene Inhibitors
• zafirlukast (Accolate)
  •   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
  • Blocks the leukotriene receptor site
    (Leukotriene receptor antagonist)
        Disadvantage of Anti-
• Inhibit one mediator pathway
• Asthma involves multiple mediators
• 50 – 70% of patients respond to the
• 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)

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