ASTHMA

• What is associated with an increase in reactivity due to allergen inhalation?


  An increase in both eosinophils and polymorphonuclear leukocytes in bronchial lavage fluid
• What are the main actions of sympathomimetic agents in asthma treatment?


  • Relax airway smooth muscle
  • Inhibit release of broncho-constricting mediators from mast cells
  • Inhibit microvascular leakage
  • Increase muco-ciliary transport
• How do adrenoceptor agonists affect intracellular cAMP levels?


  They stimulate adenylyl cyclase and increase the formation of intracellular cAMP
• What are the side effects of stimulating β2 receptors?


  Tachycardia and skeletal muscle tremor
• Which agents are classified as sympathomimetic agents for asthma treatment?


  Epinephrine, Ephedrine, Isoproterenol, and Albuterol
• What is the duration of bronchodilation for sympathomimetic agents?


  Bronchodilation occurs within 15-30 minutes and persists for 3-4 hours
• What are the adverse effects of sympathomimetic agents?


  Skeletal muscle tremor, nervousness, and weakness
• What is the action of long-acting β2 selective agonists like Salmeterol and Formoterol?

  They provide bronchodilation for 12 hours
• How is epinephrine administered for asthma treatment?

  Injected subcutaneously or inhaled as a microaerosol
• What is the onset and duration of action for epinephrine when inhaled?


  Maximal bronchodilation is achieved 15 minutes after inhalation and lasts 60–90 minutes
• What are the characteristics of Ephedrine compared to other sympathomimetics?

  It has a longer duration, oral activity, more pronounced central effects, and much lower potency
• What is the duration of action for Isoproterenol?

  60 to 90 minutes
• What are the characteristics of short-acting Beta2 Agonists (SABA)?

  • Direct-acting B2-selective agonists
  • Used to reverse asthmatic bronchoconstriction
  • Bronchodilation is maximal within 15–30 minutes and persists for 3–4 hours
  • Available in metered-dose inhalers
• What are the hallmark clinical features of asthma?

  Recurrent episodes of shortness of breath, chest tightness, and wheezing
• What are the pathophysiologic features of asthma?

  Widespread, reversible narrowing of the bronchial airways and increased bronchial responsiveness
• What are the pathologic features of asthma?

  Lymphocytic and eosinophilic inflammation of the bronchial mucosa
• What are the types of drug therapy in asthma?


  • Rescue Medications: Acute relief for asthma
  • Prophylactic Medications: Prevent exacerbations
• What is the principle in asthma treatment using drugs?


  Use the least number of drugs to control symptoms
• What factors determine drug delivery to the lungs?


  1. Size of the particles (1 – 5 um for small airways)
  2. Rate of breathing and breath holding after inhalation
• What are the advantages and disadvantages of metered dose inhalers (MDI)?


  Advantages:

  • Cheaper
  • Portable

  
  

  Disadvantages:

  • Contain chlorofluorocarbons
• What are the advantages of nebulizers in asthma treatment?

  • Do not require hand/breathing coordination
  • Can be delivered by face mask to young children and confused older patients
  • Preferred for severe asthma exacerbations
• What foreign materials provoke IgE production in asthma?

  Dust mite, cockroach, animal danders, molds, and pollens
• What happens upon reexposure to a specific allergen in asthma?

  IgE antibodies bind to mast cells, triggering the release of mediators
• What mediators are released during the early asthmatic response?

  Histamine, tryptase, leukotrienes C4 and D4, and prostaglandin D2
• What characterizes the late asthmatic response?

  It is associated with an influx of inflammatory cells and increased bronchial reactivity
• What cytokines are involved in the late asthmatic response?

  Interleukins 5, 9, and 13
• How is bronchial reactivity assessed in asthma?

  By measuring the fall in forced expiratory volume in 1 second (FEV1) after inhaling methacholine
• What is the usual regimen for theophylline dosage?

  3–4 mg/kg every 6 hours
• What is the therapeutic range for theophylline concentrations?

  10-20 mg/L
• What are the potential toxic effects of theophylline at higher levels?

  Seizure or arrhythmia at levels greater than 40 mg/L
• What are the clinical uses of theophylline?

  • Most effective bronchodilator
  • Relieves airflow obstruction in acute asthma
  • Requires monitoring due to narrow therapeutic window
• What is the mechanism of action for methylxanthines?

  Inhibition of phosphodiesterase and antagonism of adenosine receptors
• What are the three important methylxanthines?

  Theophylline, Theobromine, and Caffeine
• What is the effect of caffeine on the central nervous system?


  It causes mild cortical arousal with increased alertness
• What are the cardiovascular effects of caffeine at low concentrations?


  Inhibition of presynaptic adenosine receptors increases catecholamine release
• What happens at higher concentrations of caffeine?


  Inhibition of phosphodiesterase and increased influx of calcium
• What is the effect of theophylline on smooth muscle?

  It causes bronchodilation and inhibits antigen-induced release of histamine
• How does theophylline affect skeletal muscle?

  It strengthens contractions and improves contractility of the diaphragm
• What is the mean plasma clearance of theophylline?

  0.69 mL/kg/min
• How does the clearance of theophylline differ in children compared to adults?

  Children clear theophylline faster at 1–1.5 mL/kg/min