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Asthma has dramatically risen worldwide over the past decades, particularly in
developed countries
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Not all people with asthma have
allergies
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Asthma is most likely caused by
- genetics
- biologic triggers
- infections
- diet
- hormonal changes
- allergens
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3 major characteristics of asthma
- airway inflammation
- airway obstruction
- hyperresponsiveness of airways
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Severe persistant asthma
Days with sx, nights with sx, FEV1, PEF
- continual
- frequent
- <60%
- >30%
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Moderate Persistant Asthma
Days with sx, nights with sx, FEV1, PEF
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Mild persistent Asthma
Days with sx, nights with sx, FEV1, PEF
- >2x/week less than 1x/day
- >2x/month
- >80%
- 20-30%
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Mild Intermittent Asthma
Days with sx, nights with sx, FEV1, PEF
- <2x/week
- <2x/month
- >80%
- <20%
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Controller medications
- corticosteroids
- long acting beta agonists
- leukotriene receptor modifiers
- methylxanthines
- immunomodulators: Anti-IgE
- cromolyn and nedocrimil
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Quick relief medications
- short acting beta agonists
- systemic corticosteroids
- anticholinergic agents
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Inhaled Beta 2-agonist
- treatment of choice for mild asthma and acute exacerbations
- smooth muscle relaxation
- can prevent and reverse exercise induced bronchospasm
- more effective on an "as needed" basis
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Beta 2-agonist onset of action and duration of action
- onset = 10-15 min
- max duration 4-6 hours
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Regular use (more than ___ canister(s) per month) is assocaited with diminished control of asthma.
more than 1 canister per month
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Beta 2 Agonists relieve symptoms but do not control
inflammation
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Side effects of Beta 2 Agonists
- action on systemic B2 receptors result in increased HR, BP and EKG.
- Tremor
- Hypokalemia and hypomagnesemia with frequent use, especially in pts on thiazides
- Hyperglycemia
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Metabolism and elimination of beta 2 agonists
- metabolized by sulfotransferases
- 80-100% eliminated through renal excretion
- 20% eliminated in feces
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Methylxanthine (theophylline) mechanisms of action
- decrease phosphodiesterase
- increase cAMP
- non-specific adenosine antagonist
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Theophylline is a ____ drug and ____ is essential.
- low therapeutic index
- monitoring blood levels
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Absorption and metabolism of theophylline
- rapidly absorbed
- distributed into fat free tissues
- metabolized by the liver
- short T1/2
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Conditions effecting Theophylline metabolism
- fever
- CHF
- hepatic insufficiency
- alcohol
- neonates and adults >60 have decreased clearance
- smokers and hyperthyroidism increased clearance
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Drugs that decrease clearance of theophylline
- ticlopidine
- erythromycin
- disulfiram
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Drugs that increase clearance of theophylline
- rifampin
- phenytoin
- phenobarbital
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Decreases absorption of theophylline
food
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Theophylline level >20mcg/ml will cause
- vomiting
- arrhythmia
- intractable seizures
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Cell types inhibited by inhaled corticosteroids
- mast cells
- eosinophils
- basophils
- neutrophils
- macrophages
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Preferred drug of treatment for persistent asthma
inhaled corticosteroids
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Mechanism of action for inhaled corticosteroids
act locally in the lungs to inhibit cytokine production
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absorption and metabolism of inhaled corticosteroids
- incomplete absorption
- metabolized in the gut and liver
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ADEs with inhaled corticosteroids
- hoarsness
- thrush
- thinning of skin and increased bruising
- growth velocity slowed
- cataracts
- osteopenia in post menopausal pregnancy
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Leukotriene pathway
- Arachidonic acid + 5-Lipoxygenase activating protein => Leukotriene A4.
- LA4 + LC4 synthase => LC4
- LC4 exits the cell and binds CysLT1 receptor
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Binding CysLT1 receptor results in
- smooth muscle constriciton
- eosinophil migration
- edema
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Cys LT1 blockers
- montelukast
- pranlukast
- zafirlukast
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5-Lipoxygenase inhibitor
Zileuton
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Leukotrine receptor antagonists (monteleukast and zafirlukast)
- no known drug interactions
- tablets
- safe
- once or twice daily dosing
- not as predictable as inhaled corticosteroids
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Lipoxygenase inhibitor (ziluetin)
- metablized by CYP2C9
- Dosed 2-4x/day
- drug drug interactions with warfarin, macrolides and theophylline
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Omalizumab
- anti-IgE
- only works in patients allergic to pollen or other seasonal identified causes
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