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Acute mediators of bronchospasm
- LTC4, LTD4
- from mast cells after binding IgE antigen complex
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Chemotactant released by mast cells
LTB4
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drug class for chronic inflammation
- corticosteroids
- drugs that block release of mediators from cells; cromolyn and nedocromil
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Short acting B2 agonist
- atenolol
- terbutaline
- metaproternol
- first line of defense in acute asthma
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Long acting B2 agonist
- salmeterol
- formoterol
- slow onset of action
- 12 hours or more
- used as prophylaxis
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Beta agonist MOA
- Bind Gs coupled receptor and stimulate cAMP production
- cAMP activates protein kinase A thick phosphorilates myosin light chain kinase inactivating it
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toxicity of B agonists
- skeletal muscle tremors, not totally B2 specific
- tachycardia
- tolerance
- anxiety
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Methylxanthines
- caffeine
- theophylline, only one effective in treating asthma
- theobromine
- p450 cleared by liver
-
MOA for methyxanthines
- inhibit PDE4 and antagonizes adenosine receptor
- increases cAMP
- must used as a slow release control for nocturnal asthma
- small therapeutic index, since adenosine slows heart rhythm blocking its receptors can cause arrhythmia
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Toxicity of methyxanthines
- GI distress
- tremor
- insomnia
- large overdoses can cause arrhythmia
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Muscurinic antagonists
- atropine, not used for asthma anymore because of systemic effects
- ipratropium
- tiotropium- longer lasting
- stops phospholipase C
- used more in COPD then in acute asthma. Less toxic then B agonist in COPD, less risk of cardiovascular toxicity
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Cromolyn and nedocromil
- decrease the release of mediators; leukotrienes and histamine
- only have local effects, no absorption
- used in asthma and hey fever, can be a nasal and eye drops
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Corticosteroids
- safe if used as an inhaler, no systemic effects
- beclomethasone, flunisolide used most
- budesonide, dexamethasone, fluticasone, mometasone
-
status asmaticus
- acute asthma attack that does not respond to normal treatment
- IV prednisolone
-
MOA of corticosteroids
- reduce synthesis of arachidonic acid
- inhibits phospholipase A2
-
clinical use of corticosteroids
used in most cases of asthma that do not respond well to B agonists
-
Toxicity of corticosteroids
- aerosol may occasionally lead to slight adrenal suppression
- if given orally alternate dose to stop adrenal suppression
- more severe reactions when used for severe refractory asthma for more then two weeks
- can cause mild growth retardation , but they will recover
-
leukotriene receptor blockers
- zafirlukast and montelukast
- antagonize the LTD4 and LTE4 receptor
- orally taken and prevent exercise, antigen, and aspirin induced bronchospasms
- increase infections
-
lipoxygenase inhibitor
- zileuton
- inhibits 5 lipoxygenase, key enzyme in leukotriene synthesis
- increase infections
-
indirect sympathomimetics
- ephedrine
- release epi and norepi form stores
- produce alpha and beta reactions
- taken orally so produce systemic and cns effects
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Anti IgE antibody
Omalizumab
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Patient is on Beta blockers for heart condition and is an asthmatic
use muscurinic blockers, beta agonists would knock beta blocker off receptor and reduce its effects
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effect of cotisol on chatacholomines
- helps them bind to there receptors and stops desensitization
- give low dose with B2 agonist
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