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True or false - most of asthma is due to allergies
false - only 30%
What causes exacerbations of asthma?
decrease in expiratory airway, air is trapped or occluded
What factors cause immediate bronchospasm?
Histamine, PAF, leukotrienes (C4, D4)
What causes late bronchospasm?
mast cells, platelets, macrophages releasing chemotaxins and leuotrien B4, PAF
What are the major categories of anti asthmatic drugs?
anti inflammatory drugs
What is the mechanism of action of bronchodilator therapy?
beta-2 AR agonist
-causes decrease in Ca and decreased contractility
-hyper polarization of K
-Medication of choice
What are some selective Beta-2 AR agonists?
Why is inhalation therapy of Beta-2 AR agonists preferred?
-faster onset of action
-lower doses for effects
What are the advantages of a compressor driven nebulizer?
-consistent dose without coordination needed
-but are expensive and non portable and prone to bacterial contamination
Which B2 AR agonist can be injected subcutaneously?
What is unique about the metabolism of bitolterol?
-prodrug that is activated by lung esterases to tertbutylnorepinephrine
Which drug is the standard of inhaled beta-2 agonists for bronchospasm in asthma?
Which drug is the only beta-2 agonist that can be used by subcutaneous injection for emergency treatment of status asthmatics?
Which drug has the quickest onset of action of ant beta-2 agonist for asthma when inhaled?
Which drug has a long duration of action (8hr) when inhaled?
Which drug has the longest duration of action of any Beta2 agonist and should be used only for maintenance treatment?
What are the adverse effects of beta-2 agonists?
-Skeletal muscle tremor
-Anxiety, restlessness, apprehension
Give an example of a Methylxanthine
What is the MOA of Theophylline?
-Inhibits cAMP Phosphodiesterase, causing buildup of cAMP and Smooth Muscle Relaxation
-Antagonism of adenosine receptors
-interference with uptake and storage of Ca by SR in striated muscle, results in increase in cytoplasmic concentration of Ca ions (increase contraction of cardiac and skeletal muscle)
What affects the mean half-life of theophylline?
cigarette smoking shortens it
What is notable about Theophylline's pharmacokinetics?
narrow therapeutic window
What are adverse effects of Theophylline?
-elevated body temp
What is the MOA of Ipratropium bromide?
Muscarininc receptor antagonist
What is the biochemical effect of Ipratropium bromide?
-inhibits ACh released from airway vagal nerves
-muscarinic receptor antagonist
-decreased concentration of inositol triphosphate
-decreased release of Ca from ER = relaxation of bronchial smooth muscle
What are the clinical uses of Ipratropium bromide?
-combo with beta-2 agonists in severe acute asthma or if primary therapies are not well tolerated
-with coexisting chronic bronchitis or cough
-DOC for chornic bronchitis and emphysema
What are adverse effects of Ipratropium bromide?
-drying in the mouth post inhale
How are adrenal corticosteroids used for asthma?
-treats the chronic inflammation
-decreased inflammation will increase airway diameter
-reduced frequency and severity of chronic asthma attacks
What are examples of corticosteroids used in asthma?
What is the biochemical effect of corticosteroids?
-inhibits phospholibpase A2
-supresses arachidonic acid
-inhibits release of leukotrienes and prostaglandins
-reduces leukocyte chemotaxis and smooth muscle contraction and airway mucus secretion
What are the therapeutic uses of adrenal corticosteroids in asthma?
-first line prophylactic therapy for all cases of asthma
What are adverse effects of corticosteroids?
-rounding of facial contour
-HPA axis supression
-dryness of mouth and throat
What is an example of combination therapy ?
-mixture of glucocorticoid and long acting B-AR agonist
-Butenoside and Formototerol Fumarate
What is the clinical indication for Cromolyn sodium?
prevention of asthma attacks
-used prior to a challenge such as exercise or cold air
-wil not reverse asthmatic bronchospasm
-Combination therapy for those who do not respond well to primary lines of treatment
What is the mechanism of action of Cromolyn sodium?
-inhibits degranulation of mast cells (prevents release of histamine and other mediators)
-reduces transmembrane influx of Ca induced by IgE-antigen interaction
-Inhibits recruitment of neutrophils and eosinophils (inhibits NCF)
-Attenuates ability of PAF to cause airway hyperractivity
What are adverse effects of Cromolyn sodium?
What is the mechanism of action of Zileuton?
Inhibits synthesis of leukotreines by blocking 5-lipoxygenase
inhibits actions of LTB4
What is the mechanism of action of Zariflukast?
LT receptor antagonist
-blocks LTD4 action
What is the mechanism of action of Montelukast?
LT receptor antagonist
-blocks LTD4 action
What are the clinical indications of Zariflukast?
-prevent asthmatic attacks in patients over age of 12
-not a rescue medication
-reduces the need for rescue medications
-improves pulmonary function in mild to moderat asthma
-effective in aspirin induced asthma
-prevents cold air induced bronchoconstriction
What are contraindications of Zariflukast?
What are drug interactions of Zariflukast?
any CYP450 metabolized drug
what are the clinical uses of Zileuton?
-prevent exercise, cold air, and aspirin induced asthma
-reduces nocturnal symptoms
What are the adverse effects of Zileuton?
-inc. alanine transaminase
-contraindicated with hepatic disease
What is the mechanism of action of omalizumab?
-forms a complex with circulating IgE to lower serum concentration levels and prevent IgE from biding to mast cells
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