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Anti-Inflammatory and Anti-asthmatic Agents. MODULE F. Objectives. 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.

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Anti inflammatory and anti asthmatic agents

Anti-Inflammatory and Anti-asthmatic Agents

MODULE F


Objectives
Objectives

  • 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.


Objectives1
Objectives

  • 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.


Objectives2
Objectives

  • 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.


Objectives3
Objectives

  • 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
Anti-Inflammatory Drugs

  • Non-Steroidal Anti-inflammatory

    • Mast Cell Stabilizers or anti-asthmatics

    • Leukotriene Antagonists (anti-leukotrienes)

  • Adrenocorticosteroid Anti-inflammatory

    • Corticosteroids or Steroids


Mechanism of inflammation
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 inflammation1
Mechanism of Inflammation

  • Mediator Release

    • Bronchospasm

    • Vasodilation resulting in mucosal edema

      • Increased vascular permeability

    • Increased mucus gland secretion


Mediators of inflammation
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



Phases of inflammatory response in asthma
Phases of Inflammatory Response in Asthma

  • Early phase - Immediate

  • Late phase – 6 to 8 hours after exposure


Early phase
Early Phase

  • Local vasodilation

  • Increased vascular permeability

  • Redness

  • Bronchoconstriction

  • Wheezing

  • Coughing

  • Dyspnea

  • Hypoxemia


Late phase
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



Goal of therapy
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
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
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
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
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
nedocromil sodium (1992)

  • Tilade

  • MDI:

    • 1.75 mg/inhalation

    • 2 inhalations QID

  • Side Effects similar to cromolyn


Adrenocorticosteroids
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 Gland

ADRENAL CORTEX


Hpa axis
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.



Hpa axis1
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
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
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
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
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




Adverse reactions of aerosolized steroids
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
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 ModifiersAnti-LeukotrienesLeukotriene AntagonistsLeukotriene Inhibitors


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 inhibitors1
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 inhibitors2
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 inhibitors3
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 anti leukotrienes
Disadvantage of Anti-leukotrienes

  • Inhibit one mediator pathway

  • Asthma involves multiple mediators

  • 50 – 70% of patients respond to the medication

  • Trial & Error


Upper airway congestion
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
IGE Inhibitors

  • omalizumab (Xolair)


Dosing
Dosing

  • http://www.xolair.com/hcp/dosing_calculator2.jsp


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