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23 Cards in this Set
- Front
- Back
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Pathological Findings of Asthma
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Contracted airway smooth muscle, mucousal thickening from edema and cellular infiltration, mucous plugs block smaller airways
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Pathophysiology of Asthma
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1. Release of chemical mediators from mast cells and eosinophils (histamine, leukotrienes, TXA2, PGs)
2. Abnormality in regulation of smooth muscle tone (increased cholinergic activity) 3. Chronic airway inflammation (increased number of inflammatory cells even between acute attacks) |
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Allergen causing immediate granule content release
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Histamine, proteases, heparin, TNF
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Membrane derived lipid mediators
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(over minutes)- PGs, leukotrienes, platelet activating factor (PAF)
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Cytokine production
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Over hours- Interleukins, IL2,3,4,5,6,8 and TNF
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Cell infiltration
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Eosinophil- ECP, MBP
Neutrophil- Proteases, PAF Expand tissue and cause edema |
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Signs/Symptoms of Asthma
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Wheezing, coughing, tachypnea (rapid breathing), dyspnea (labored breathing)- using chest muscles along with diaphragm
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Drug classes that Reverse Bronchospasm
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Beta2 agonist, ipratropium (muscarinic antagonist), theophylline
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Drugs that remove trigger or antigen
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Cromolyn, Nedocromil
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Drugs that control inflammation
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Steroids, lipoxygenase inhibitors
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Beta2 agonists
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Independent of stimulus. Includes: albuterol, levalbuterol, metaproterenol, and pirbuterol.
Long acting (30 min onset, 12 hours): Salmeterol, Formoterol |
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Adverse effects fo B2 Agonists
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Tachycardia, hypotension, headache, dizziness, insomnia, tremors, hyperglycemia
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Ipratropium Bromide
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Nonselective muscarinic antagonist on bronchial smooth muscle (m3), slower onset and less bronchodilation than B2 agonists
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Tiotropium
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used in COPD and emphysema
Adverse effects include palpitations, blurred vision, dry mouth, bronchospasm |
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Theophylline
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used in COPD
1) Inhibit phosphodiesterase 4 and 5, increase cAMP and cGMP 2) Adenosine receptor (A2B) antagonist 3) Anti inflammatory actions inhibit inflammatory mediators in late response |
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Adverse effects if Theophylline
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Requires alot of monitoring!
Stimulant gastric acid, diuretic effects, smooth muscle relaxant, CNS stimulant- convulsions in doses > 20mcg/ml, cardiac stimulant- arrhythmias in doses > 20mcg/ml |
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Plasma level monitoring of Theophylline
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5-20 ug/ml: therapeutic levels
15-20 ug/ml: nausea, vomiting, cardiac effects 30-40 ug/ml: toxic effects- seizures, arrhythmias, possibly death |
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Cromolyn, Nedocromil
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-Both inhalation
-Remove trigger or antigen -Stabliize mast cells: limited use -Must be taken before antigen insult -Mechanism unknown, but may interefere with Ca++ |
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Corticosteroids
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beclomethasone, budesonide, flunisolide, fluticasone, mometasone, triamcinolone
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Mechanism of Corticosteroids
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Inhibit anti-inflammatory cascade
Up to 8 weeks for maximal effects adverse effects: oral candidiasis(thrush), suppress growth in children (high dose), inhibit immune system (systemic action) |
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Oral Leukotriene Antagonists
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Zafirlukast, Montelukast
-LTD4 antagonist (cysLT1 receptor): receptor mediates inflammation, bronchial constriction, mucous secretion -Zafirlukast inhibits CYP2C9 and 3A4 while Montelukast does not -Effective in ASA induced asthma |
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Zileuton
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-Very seldom used
-5-lipoxygenase inhibitor -Adverse effects: flu-like syndrome, drowsiness, hepatic enzyme elevation, inhibits CYP1A2 and 3A4 |
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Omalizumab
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SQ 3-4 weeks
-Recombinant DNA derived humanized IgE monoclonal antibody -Binds circulating IgE which decreases high affinity receptors on mast cells, prevents degranulation -Adverse effects: GI disturbances, anaphylaxis, secondary malignancies |
