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71 Cards in this Set
- Front
- Back
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during the 1st wave in allergic asthma, what cells are activated initially?
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alveolar macrophages/ mast cells
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during the 1st wave in allergic asthma, what do macrophages secrete? what do mast cells do?
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macrophages--> cytokines TNF alph and GM-CSF
mast cells - release preformed mediators: Histamine, remodeling enzymes, TNFalpha. |
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what does effect does histamine have on the body?
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bronchoconstriction, vasodilation, mucous secretion
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what do remodeling enzymes do?
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breakdown ECM
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Two things occur during the 2nd wave of allergic asthma, what are they?
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chemotaxis and mast cells releasing induced mediators of inflammation
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What endothelial alterations occur during chemotaxis?
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1) sticky- increased adherence of neutrophils so those immune cells can adhere
2) leaky- endothelial cells separate so different immune cells can get thru. |
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what occurs during chemotaxis in the 2nd wave of allergic asthma?
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endothelial alterations
neutrophils activated capillaries dilate increased synthesis of leukocytes |
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what do macrophages secrete during the 2nd wave of allergic asthma?
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GM-CSF
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when do the mast cells released induced mediators of inflammation?
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hours later
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what reaction do leukotrienes induce?
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bronchoconstriction, vasodilation, mucous secretion
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what are the induced mediators of inflammation that are released by mast cells?
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leukotrienes
PGs IL-4 IL-5 |
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what effects do prostaglandins have on the body?
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pain, bronchoconstriction, vasodilation, chemotaxis
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which Interleukin induced IgE synthesis?
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IL-4
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In the chronic late phase of a pt with allergic asthma, what will you most commonly see?
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hyper-reactivity of airways to triggers, increased Th2 cell activity and eosinophil degranulation
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what cells mediate chronic reactivity in allergic asthma?
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T cells and eosinophils
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Non-specific bronchial hyperreactivity has two associated components, what are they?
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inflammatory and neural
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what does the increased Th2 cell activity sustain in the chronic phase of allergic asthma?
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sustains IgE synthesis, mast cell and eosinophil activity
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what type of HSN can be seen in chronic late phase allergic asthma?
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HSN 4
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T/F
Particle size is negligible to the delivery to the lungs via aerosol |
FALSE
Particle size is critical to delivery to the lungs-> larger particles that cannot go into the lungs will be desposited on the tongue and throat |
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what is the function of a spacer?
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to facilitate drug delivery and prevent deposition of large drug particles in the mouth which may be swallowed leading to systemic effects.
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what two qualities should the drug have in order to minimize systemic effects?
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should be poorly absorbed from GI system and be rapidly inactivated via first-pass metabolism
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which receptor are we most concerned for in the tx of asthma?
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B2 on the smooth vasculature of the lungs
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what is the most important pharmacologic action of B2 adrenergic receptor agonists? what other pharmacological action does it have?
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relaxation of airway smooth muscle. ALso inhibits the release of bronchoconstricting mediators from mast cells.
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why don't we see downregulation of the beta 2s in the lungs?
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due to the large number of spair receptors located on the smooth muscle of the lungs.
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what affect does arginine at position 16 have on short or long-term B2 AR agonists?
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increases the risk for exacerbations
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what type of receptor do B2-Adrenergic agonists bind to?
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beta2- adrenergic receptor which is a seven transmembrane G-protein couple, serpentine receptor
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what does the Galpha/ GTP complex activate? what does this lead to?
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adenylate cyclase--> increased intracellular cAMP --> activates PKA --> decreases intracellular calcium level by enhancing Ca2+ uptake by the ER --> relaxation
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prolonged stimulation of the Galpha/GTP complex can lead to what? how come this isn't a problem on the bronchioles?
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down-regulation (tolerance); B2ARs on bronchioles are resistant to tolerance at therapeutic doses
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what are the three short-acting specific B2-AR agonists? what are they used for?
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albuterol, levalbuterol, pirobuterol... used for rescue events, not for maintenance
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what are the two long-acting specific B2-AR agonists? what must these be paired with?
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salmeterol and formoterol... must be paired with a glucocorticoid
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what are the two long-acting specific B2 AR agonists that are reserved for special situations due to adverse effects? how is it administered?
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epinephrine and isoproterenol
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why don't we use oral B-AR agonists?
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there is a greater incidence of SE vs inhaled (like tremulousness, muscle cramps, tachyarrhythmias)
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Tricyclic antidepressant + salmeterol cause adverse drug rxn because it causes an increase in what?
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catecholamines
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what do MAO-I's cause?
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increased circulating sympathetics
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what five categories of disorders should cause you to pause before giving them any B2 AR agonists?
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cardiovascular disorders*, convulsive disorders*, diabetes mellitus*, hyperthyroidism, hypokalemia
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what are the three inhaled glucocorticoids used to tx asthma?
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budesonide, fluticasone, and triamcinolone
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what are the two systemic glucocorticoids used to tx asthma?
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prednisone and methylprednisolone
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why are glucocorticoids effective for tx asthma?
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via their anti-inflammatory activity.
suppression of proinflammatory genes and increased expression of anti-inflammatory genes |
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what are the two most common adverse Drug rxn w/ inhaled glucocorticoids?
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oropharyngeal candidiasis and pharyngitis
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what are the precautions before prescribing a glucocorticoid?
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active fungal, viral or bacterial infections; ocular herpes simplex, glaucoma.
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what are the two combo inhalers?
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salmeterol-fluticasone; formoterol-budesonide
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oral corticosteroids should be used with caution in pts with?
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concomitant use of other agents metabolized w/ CYP450 3A4, diabetes mellitus, Peptic ulcer disease, osteoporosis.
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what are the two chromones? what is their mechanism of action?
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cromolyn sodium and nedocromil sodium; It's not really understood, but it prevent mast cell degranulation and inhibits the activation of a chloride current in cells undergoing shape and volume changes associated with immune cell activation.
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what is a good prophylaxis for exercise induced asthma?
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chromones--> cromolyn sodium, nedocromil sodium
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what are the precautions associated with chromones?
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less than 2 years, cardiac arrhythmias, CAD.
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what are the two categories of leukotriene modulators used to tx asthma? what drugs fit these categories?
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LT receptor antagonists:
- zafirlukate, montelukast LT synthesis inhibitors: Zileuton |
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T/F
Histamine is 1,000 times more potent than Leukotrienes |
FALSE
Leukotrienes are 1,000 times more potent than histamine |
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how do leukotrienes differ from histamine?
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leukotrienes are induced, not pre-formed mediators of inflammation
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what do LT receptors look like? what other receptor does this resemble?
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serpentine, 7 transmembrane spanning domain, G protein-coupled receptor. It resembles the B2-AR
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what category of drugs falls under the category of leukotriene receptor antagonists? what do they cause?
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CysLT1- competitively blocks the effects of leukotriene binding to CysLT1 causing decreased bronchoconstriction, decreased vasodilation, decreased mucus secretion.
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what do leukotriene synthesis inhibitors do?
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inhibit 5-lipoxygenase causing decreased bronchoconstriction, decreased vasodilation and decreased mucus secretion.
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what are the two categories of leukotriene modulators?
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leukotriene receptor antagonists, leukotriene synthesis inhibitor.
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what are the adverse drug reactions associated with mast cell stabilizers?
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elevated liver enzymes (Zileuton), nausea, and neuropsyciatric events
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what are the subcategories of mast cell stabilizers?
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chromones, leukotriene modulators, leukotriene receptors, and leukotriene inhibitors
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what is the route of administration for all mast cell stabilizers?
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oral
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Zileuton decreases the clearance of what two drugs?
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warfarin and theophyllin
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what two drugs used to tx asthma are substrates and potent inhibitors of CYP450 2C9 and 3A4 isoenzymes?
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zafirlukast and zileuton
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how is contraction of smooth muscle caused via mast cell stabilizers acting of M3 receptors?
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the mast cell stabilizers activated M3 --> activated PLC --> IP3 --> calcium released from SR --> elevated intracellular calcium ---> contraction
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what is the purpose of the muscarinic receptor antagonists?
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to restore the normal tone of bronchial smooth muscle that is under excess cholinergic stimulation to normalize airway diameter.
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what does ipratropium block?
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all muscarinic receptor subtypes (its also short-acting)
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which asthma tx selectively blocks M1 and M3 subtypes and is a long-acting drug?
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tiotropium
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what is the mechanism of action of theophylline? what category does theophyllin fall into?
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blocks PDEs and increases Tissue concentrations of cAMP and its an antagonist at adenosine receptors. Methylzantine category
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why does theophylline have so many SEs?
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because it is not a specific PDE- inhibitor
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why is decreased clearance of theophylline such a big deal?
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Theophylline has a very narrow therapeutic window and as it concentrates over 15 mg, the pt starts to develop uncomfortable GI symptoms. At higher levels it can cause seizures or cardiac arrhythmias.
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what drug falls under the anti IgE antibodies category? what is it?
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omalizumab- humanized monoclonal ab against the Fc region of IgE ab.
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what is the aim of omalizumab? what are the long-term risks involved?
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bind up all the IgE in the body and remove it from the body so it cannot have an effect. Long-term--> disproportionate increase in CV disorders and maybe cancer.
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T/F
Both asthma and COPD are reversible lung disorders. |
FALSE
asthma- reversible COPD- irreversible |
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what is the pathogenesis of COPD?
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small air way fibrosis--> obstruction of airways/ destruction of alveoli --> increased mucous secretion --> chronic inflammation --> increased numbers of macrophages, neutrophils, and T-lymphocytes --> decreased effective area for transfer of gasses.
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T/F
there are no current txs to slow the progression of COPD. |
sadly, true
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what three areas in COPD can be txed pharmacologically?
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mucous secretion
chronic inflammation hypertrophied smooth muscle |
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what two categories of drugs are used for COPD pts?
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bronchodilators (short and long) and corticosteroids.
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