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