Transcript Mediator Antagonists

Mediator Antagonists
Chapter 12
Mechanisms of inflammation in
asthma

1.
2.

Types of asthma
Extrinsic dependent on allergies
Intrinsic shows no sensitization to allergens
With both forms airway inflammation is evident
causing bronchoconstriction, airway swelling,
mucus secretion and obstruction
Allergic response
Primarily involves mast cells and
immunoglobin E
 Lymphocytes (T cells) activated by an
antigen result in the production of IgE
 IgE binds to mast cells
 Releases mediators of inflammation such
as prostaglandins, leukotrienes, histamine,
platelet aggregating factor, and cytokines

Allergic response
Mediators from mast cell cause vascular
leakage, bronchoconstriction, mucus
secretion, and mucosal swelling
 Once initiated the inflammatory response
causes the release of eosinophils,
neutrophils, and lymphocytes which
increase the severity of the inflammation

Disodium
cromoglycate/Cromolyn sodium
Comes from the seeds of a plant Ammi visagna
 Extract of khellin taken from here-originally used
to treat colic
 Prophylactic agent to prevent asthmatic
reactions
 Not related to any other drug category such as
beta agonists, xanthines, or glucocorticoids

Indications for use
Prophylactic management of asthma
 Prevention of exercise induced asthma
 For allergic rhinitis
 Extrinsic asthma

Mode of action






Prevents mast cell degranulation
Blocks release of chemical mediators
Must be used as a pretreatment
May work by preventing calcium from allowing
the contraction of the filaments on the mast cell
which release the mediators
Does not work as an antagonist on the
mediators themselves
Does not affect alpha or beta receptors
Mode of action cont.

Does not prevent antibody formation, the
attachment of IgE, and the combination
of antibody-antigen reactions-only
prevents the release of the mediators
Dosage and administration
Spinhaler (dry powder inhaler)-can be
irritating and cause coughing or
bronchoconstriction. May need beta 2
agonist prior to or after tx.
 Ampule for nebulization (20 mg/2ml).
Brand names Aarane or Intal
 MDI
 Nasal solution(Nasalcrom)

Side Effects
Safe drug
 Dry powder causes throat irritation,
hoarseness, dry mouth
 Nebulizers associated with cough,
wheezing, sneezing

Clinical Applications
Drug is only prophylactic and should not
be used during acute bronchospasm. No
bronchodilating action.
 No affect on the adrenal system and can’t
be used as replacement for corticosteroids
 May take 2 to 4 weeks for improvement
in patient’s symptoms

Nedocromil sodium (Tilade)
Cromolyn sodium type drug
 Prophylactic therapy for asthma
management
 Inhibits mast cell mediator release
 Can inhibit eosinophil activity

Leukotrienes
Production from leukocytes.
 Release of leukotrienes during
inflammatory reaction causes narrowed
airways, excessive mucus production,
airway inflammation

Role of leukotrienes in asthma
Leukotrienes originally called SRSA
 Released by inflammatory cells
 Directly contract airway smooth muscle
 1000 x more potent than histamine in
causing bronchial contraction and the
contraction lasts longer
 Also stimulate hypersecretion of mucus

Leukotrienes

Also stimulate vascular permeability which
causes airway swelling
Antileukotriene therapy
Inhibit the production and block the action
of leukotrienes
 Two main classes: leukotriene synthesis
inhibitors and leukotriene receptor
antagonists

Pharmacologic agents
Montelukast (singulair)
 Leukotriene receptor antagonist
 Blocks leukotrienes at receptor site
 Improves airway obstruction, may keep
episodes from worsening in chronic
asthma

Pharmacologic agents
Zafirlukast (Accolate)
 Receptor antagonist used in the tx of
chronic asthma
 Inhibits bronchoconstriction.

Pharmacologic agents
Zileuton (Zyflo)Inhibits formation of
leukotrienes
 Inhibits bronchoconstriction caused by
various allergens

Side effects
Accolate(Zafirlukast)-headache, nausea,
diarrhea, abdominal pain, infection
 Zileuton(Zyflo)-headache, abdominal pain,
loss of strength, stomach upset
 Montelukast(Singulair)- does not have
these side effects
