Post on 20-Jan-2016
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Mediator AntagonistsMediator Antagonists
Chapter 12Chapter 12
Mechanisms of Mechanisms of inflammation in asthmainflammation in asthma
Types of asthmaTypes of asthma
1.1. Extrinsic dependent on allergiesExtrinsic dependent on allergies
2.2. Intrinsic shows no sensitization to Intrinsic shows no sensitization to allergensallergens
With both forms airway inflammation is With both forms airway inflammation is evident causing bronchoconstriction, evident causing bronchoconstriction, airway swelling, mucus secretion and airway swelling, mucus secretion and obstructionobstruction
Allergic responseAllergic response
Primarily involves mast cells and Primarily involves mast cells and immunoglobin Eimmunoglobin E
Lymphocytes (T cells) activated by an Lymphocytes (T cells) activated by an antigen result in the production of IgEantigen result in the production of IgE
IgE binds to mast cellsIgE binds to mast cells Releases mediators of inflammation Releases mediators of inflammation
such as prostaglandins, leukotrienes, such as prostaglandins, leukotrienes, histamine, platelet aggregating factor, histamine, platelet aggregating factor, and cytokinesand cytokines
Allergic response Allergic response
Mediators from mast cell cause Mediators from mast cell cause vascular leakage, vascular leakage, bronchoconstriction, mucus bronchoconstriction, mucus secretion, and mucosal swellingsecretion, and mucosal swelling
Once initiated the inflammatory Once initiated the inflammatory response causes the release of response causes the release of eosinophils, neutrophils, and eosinophils, neutrophils, and lymphocytes which increase the lymphocytes which increase the severity of the inflammationseverity of the inflammation
Disodium Disodium cromoglycate/Cromolyn cromoglycate/Cromolyn
sodiumsodium Comes from the seeds of a plant Ammi Comes from the seeds of a plant Ammi
visagnavisagna Extract of khellin taken from here-Extract of khellin taken from here-
originally used to treat colicoriginally used to treat colic Prophylactic agent to prevent asthmatic Prophylactic agent to prevent asthmatic
reactionsreactions Not related to any other drug category Not related to any other drug category
such as beta agonists, xanthines, or such as beta agonists, xanthines, or glucocorticoidsglucocorticoids
Indications for useIndications for use
Prophylactic management of asthmaProphylactic management of asthma Prevention of exercise induced Prevention of exercise induced
asthmaasthma For allergic rhinitisFor allergic rhinitis Extrinsic asthmaExtrinsic asthma
Mode of actionMode of action
Prevents mast cell degranulationPrevents mast cell degranulation Blocks release of chemical mediatorsBlocks release of chemical mediators Must be used as a pretreatmentMust be used as a pretreatment May work by preventing calcium from May work by preventing calcium from
allowing the contraction of the filaments allowing the contraction of the filaments on the mast cell which release the on the mast cell which release the mediatorsmediators
Does not work as an antagonist on the Does not work as an antagonist on the mediators themselvesmediators themselves
Does not affect alpha or beta receptorsDoes not affect alpha or beta receptors
Mode of action cont.Mode of action cont.
Does not prevent antibody formation, Does not prevent antibody formation, the attachment of IgE, and the the attachment of IgE, and the combination of antibody-antigen combination of antibody-antigen reactions-only prevents the release reactions-only prevents the release of the mediatorsof the mediators
Dosage and administrationDosage and administration
Spinhaler (dry powder inhaler)-can Spinhaler (dry powder inhaler)-can be irritating and cause coughing or be irritating and cause coughing or bronchoconstriction. May need beta bronchoconstriction. May need beta 2 agonist prior to or after tx.2 agonist prior to or after tx.
Ampule for nebulization (20 mg/2ml). Ampule for nebulization (20 mg/2ml). Brand names Aarane or Intal Brand names Aarane or Intal
MDIMDI Nasal solution(Nasalcrom)Nasal solution(Nasalcrom)
Side EffectsSide Effects
Safe drugSafe drug Dry powder causes throat irritation, Dry powder causes throat irritation,
hoarseness, dry mouthhoarseness, dry mouth Nebulizers associated with cough, Nebulizers associated with cough,
wheezing, sneezingwheezing, sneezing
Clinical ApplicationsClinical Applications
Drug is only prophylactic and should Drug is only prophylactic and should not be used during acute not be used during acute bronchospasm. No bronchodilating bronchospasm. No bronchodilating action.action.
No affect on the adrenal system and No affect on the adrenal system and can’t be used as replacement for can’t be used as replacement for corticosteroidscorticosteroids
May take 2 to 4 weeks for May take 2 to 4 weeks for improvement in patient’s symptomsimprovement in patient’s symptoms
Nedocromil sodium (Tilade)Nedocromil sodium (Tilade)
Cromolyn sodium type drugCromolyn sodium type drug Prophylactic therapy for asthma Prophylactic therapy for asthma
managementmanagement Inhibits mast cell mediator releaseInhibits mast cell mediator release Can inhibit eosinophil activityCan inhibit eosinophil activity
LeukotrienesLeukotrienes
Production from leukocytes.Production from leukocytes. Release of leukotrienes during Release of leukotrienes during
inflammatory reaction causes inflammatory reaction causes narrowed airways, excessive mucus narrowed airways, excessive mucus production, airway inflammationproduction, airway inflammation
Role of leukotrienes in Role of leukotrienes in asthmaasthma
Leukotrienes originally called SRSALeukotrienes originally called SRSA Released by inflammatory cellsReleased by inflammatory cells Directly contract airway smooth muscleDirectly contract airway smooth muscle 1000 x more potent than histamine in 1000 x more potent than histamine in
causing bronchial contraction and the causing bronchial contraction and the contraction lasts longercontraction lasts longer
Also stimulate hypersecretion of mucusAlso stimulate hypersecretion of mucus
LeukotrienesLeukotrienes
Also stimulate vascular permeability Also stimulate vascular permeability which causes airway swellingwhich causes airway swelling
Antileukotriene therapyAntileukotriene therapy
Inhibit the production and block the Inhibit the production and block the action of leukotrienesaction of leukotrienes
Two main classes: leukotriene Two main classes: leukotriene synthesis inhibitors and leukotriene synthesis inhibitors and leukotriene receptor antagonistsreceptor antagonists
Pharmacologic agentsPharmacologic agents
Montelukast (singulair)Montelukast (singulair) Leukotriene receptor antagonistLeukotriene receptor antagonist Blocks leukotrienes at receptor siteBlocks leukotrienes at receptor site Improves airway obstruction, may Improves airway obstruction, may
keep episodes from worsening in keep episodes from worsening in chronic asthmachronic asthma
Pharmacologic agentsPharmacologic agents
Zafirlukast (Accolate)Zafirlukast (Accolate) Receptor antagonist used in the tx of Receptor antagonist used in the tx of
chronic asthmachronic asthma Inhibits bronchoconstriction.Inhibits bronchoconstriction.
Pharmacologic agents Pharmacologic agents
Zileuton (Zyflo)Inhibits formation of Zileuton (Zyflo)Inhibits formation of leukotrienesleukotrienes
Inhibits bronchoconstriction caused Inhibits bronchoconstriction caused by various allergensby various allergens
Side effectsSide effects
Accolate(Zafirlukast)-headache, Accolate(Zafirlukast)-headache, nausea, diarrhea, abdominal pain, nausea, diarrhea, abdominal pain, infectioninfection
Zileuton(Zyflo)-headache, abdominal Zileuton(Zyflo)-headache, abdominal pain, loss of strength, stomach upsetpain, loss of strength, stomach upset
Montelukast(Singulair)- does not Montelukast(Singulair)- does not have these side effectshave these side effects