PHRM 825: Asthma - Hazbun Flashcards
How are mast cells activated?
Cross linking of the Fc receptor and IgE via an antigen
What do mast cells release?
PGD2, LTC4, LTD4, Histamine, tryptase
What causes the early reaction in asthma?
Antigen binding to IgE antibodies triggering degranulation of mast cells
What causes the delayed reaction in asthma?
Activation of TH2 lymphocytes
What do eosinophils contain a lot of?
histamine molecules
Which receptors cause the development of hyperplasia?
EGFR and CLCA
Which receptor causes the maintenance of hyperplasia?
Bcl-2
What polymorphism contributes to goblet cell hyperplasia?
R576 polymorphism in the IL-4alpha receptor
What polymorphism induces hyperreactivity to inhaled antigens?
Q576R in the IL-4alpha receptor
Which receptors are upregulated in asthma?
IL-13
What happens to the epithelium during airway remodeling?
Mucous hyperplasia and hypersecretion
What happens to the basement membrane during airway remodeling?
It thickens
What happens to the smooth muscle during airway remodeling?
It undergoes hypertrophy (increase in size, NOT NUMBER of cells)
What are 3 results of COPD?
- Fibrosis of small airways
- Alveolar wall destruction (aka emphysema)
- Mucus hypersecretion
What are the main 3 places that the CFTR channel is expresses?
- Airway epithelium
- Sweat duct epithelium
- Pancreatic duct epithelium
What is an early sign of CF and what causes it?
Excessively salty sweat - caused by loss of CFTR function
What are the 2 treatment strategies in asthma?
- Bronchodilation
- Anti-inflammation
What is a prevention strategy for asthma?
Inhibition of mast cell degranulation
SABAs are resistant to what enzymes?
COMT
LABAs are resistant to what enzymes?
COMT and MAO
What is the administration route of choice for acute attacks?
Inhalation
What is one advantage of using inhaled products versus oral products?
Fewer systemic adverse effects
What medications are contraindicated as monotherapies in asthma but not COPD?
LABAs (e.g. salmeterol and formoterol)
What do glucocorticoids do?
Decreases the hyperresponsiveness of bronchial smooth muscle cells that occurs in chronic asthma
Which medication has a narrow therapeutic range?
Theophylline (10-15mcg/mL)
Pre-treatment with Cromolyn sodium and Nedocromil sodium prevents asthma attacks by blocking what?
bronchoconstriction caused by antigen inhalation, exercise, aspirin, and environmental toxins
How does Xolair work?
Inhibits binding of IgE antibodies to the Fc(epsilon)R1 Receptor on mast cells and basophils inhibiting degranulation
What is an important AE of Zileuton?
- Doubles the blood levels of theophylline
- Causes increase in prothrombin time of patients taking warfarin
What 4 drug classes can be used to treat COPD?
- Inhaled muscarinic receptor antagonists
- Long-acting beta2-adrenergic agonists
- Short-acting beta2-adrenergic agonists
- Alpha1-antitrypsin replacement (rare)
What are 2 muscarinic antagonist medications?
Ipratropium and Tiotropium
Quaternary ammonium compounds that limit systemic absorption
What 3 things happen during lung remodeling in COPD?
- Fibrosis of small airways
- Hyperinflation of lungs (alveolar wall destruction)
- Mucus hypersecretion
What genetic deficiency occurs in <1% of COPD patients?
Alpha 1 antitrypsin
What medications are used to treat alpha 1 antitrypsin deficiency?
- Prolastin
- Aralast
- Zemaria
Where is the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) expressed?
- Airway epithelium
- Sweat duct epithelium
- Pancreatic duct epithelium
What happens to the CFTR protein in most CF cases?
Defective processing - it never reaches the membrane surface
What drug is used to treat CF in the small subset of patients?
Ivacaftor
What drug classes are used to treat CF in the majority of patients?
Mucolytics (Dornase alfa, Pulmonase, Mucomyst, Hypersal)
Bronchodilators (albuterol)
Antibiotics (Tobramycin and azithromycin)
