Clinical Case 1 By E.B. Andaya

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Clinical Case 1ByE.B. Andaya

• A 15 year old male presents to pediatric chest
  clinic for evaluation. He has story of
  intermittent wheezing (approximately 6-8/yr.)
  frequently provoked by exposure to cats or eating
  chocolate. There is a strong family history of
  allergies. Routine spirometry is within normal
  limits and peak flow is 350L/min. He is seen
  again 2 weeks later with acute onset of wheezing,
  peak flow 280L/min.

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• Subjective findings wheezing
• Diagnosis Asthma
• Differential Diagnosis
• Nocturnal awakening
• upper airway obstruction by tumor or laryngeal
  edema
• glottic dysfunction
• acute left ventricular failure
• endobronchial disease

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• Asthma
• chronic inflammatory disease of airways
  characterized by increased tracheobronchial tree
  responsiveness to a multiplicity of stimuli
• manifested by widespread narrowing of air
  passages which may be relieved spontaneously or
  as a result of therapy and clinically by
  paroxysms of dyspnea, cough, and wheezing
• episodic disease, with acute exacerbations
  interspersed with symptom free periods

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• Symptoms dyspnea, cough, wheezing
• Stimulants
• allergenic
• pharmacologic
• environmental
• Occupational
• Infections
• exercise related
• emotional

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• What is the basis of the bronchial responsiveness
  in asthmatic subjects?
• Disease mediated by IgE Ab bound to mast cells in
  airway mucosa
• Re-exposure to Ag ? Ag-Ab interaction on surface
  of mast cells triggers
• Release of mediators stored in cells granules
• Synthesis release of other mediators
• Agents for immediate bronchoconstriction (His,
  Tryptase, PGD2, LTC4, PAF)

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• What bronchodilator drugs are used in asthma?
  Give examples.
• ß-adrenergic Receptor Agonists
• Short acting
• Albuterol
• Levalbuterol
• Metaproterenol
• Terbutaline
• Pirbuterol
• Long acting
• Salmeterol xinafoate
• Bitolterol
• Non-selective ß-agonists
• Epinephrine
• Ephedrine
• Isoproterenol
• Muscarinic Antagonists Ipatropium Bromide
• Methylxanthines Theophylline

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• What intracellular transduction mechanisms are
  involved in the action of the main bronchodilator
  drugs?
• Mechanism of ß-agonists ? activation of adenylyl
  cyclase ? ATP conversion to cAMP
• Activation of cyclase enzyme is mediated by
  stimulatory coupling protein Gs
• cAMP major 2nd messenger of ß-receptor
  activation
• ß-receptor activation promotes relaxation of
  smooth muscle
• Best-characterized action ? relaxation of smooth
  muscle ? bronchodilation
• Stimulation of ß2-receptors
• relaxes airway smooth muscle
• inhibits mediator release
• causes skeletal muscle tremor as a toxic effect

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ATP
ß-agonist
AC

Bronchodilation
cAMP

Bronchial tone
PDE
AMP
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Which anti-asthma drugs can be given by
inhalation and which cannot? How are this latter
agents given?
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Drug Specific Drug Inhalant Oral Parenteral
Bronchodilators Albuterol Bitolterol Ephedrine Epinephrine Isoproterenol Levalbuterol Metaproterenol Pirbuterol Salmeterol Tertbutaline X X X X X X X X X X X X X X X X X
Corticosteroids Beclomethasone Budesonide Flunisolide Mometasone X X X X
Cromolyn Na Nedocromil Na X
Methylxanthines Theophylline X X
Antimuscarinic Ipratropium X
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• What is the role of Sodium Cromolglycate in the
  treatment of asthma and what is its mechanism of
  action?
• Blocks bronchoconstriction caused by
• Antigen inhalation
• Exercise
• Aspirin
• Variety of causes of occupational asthma
• Mechanism of action inhibits release of histamine
  in mast cells.