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59 Cards in this Set
- Front
- Back
COPD is irreversible, clinically showing as emphysema or chronic bronchitis. Main cellular response is
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neutrophilic and monocytic
(neutrophils and resident macrohages release proteinases, particularly matrix metalloproteinases. |
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Main cellular response of astma is:
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CD4 T lymphocytes
B lymphocytes mast cells eosinophils |
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Beta 2 adrenergic receptors are activated by epinephrine which is secreted by the adrenal medulla and causes
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bronchodilation
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M3 receptors in airway smooth muscle when stimulated by acytelcholine can cause
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bronchoconstriction
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NANC fibers release neuropeptides including:
Neurokinin A, calcitonin gene related peptide, substance P, bradykinin, tachykinin and neuropeptide Y All of which cause |
bronchoconstriction
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NANC fibers release neuropeptides including:
Nitric oxide and Vasoactive intestinal polypeptide (VIP) All of which cause: |
bronchorelaxation
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_____ _______ Is a marker of the intensity of airway inflammation, and measurements have been used to assess the severity of asthma to titrate therapy accordingly.
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Nitric Oxide
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Inhaled corticosteroid use in COPD
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Is not a statistically significant benefit
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Cytokines produced by CD4 Th1 cells
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INF y
IL 2 TNF a |
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Cytokines produced by CD4 Th2 cells
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IL4
IL5 IL6 IL9 IL13 |
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What type of CD4 Th cells guide the immune response towards a cellular response involving Th adn Tc cells?
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Th1
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What type of CD4 Th cells guide the immune response towards a humoral response based on ab production by B cells?
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Th2
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Th1 or Th2 predominates in Asthma?
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Th2
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Hypersensitivity vs Hyperreactivity
How do they each shift the stimulus response curves? |
Hypersensitivity- normal response at abnormally low levels of stimuli, possibly due to increase activity of mosin light chain kinase in asthma patients (left shift)
Hyperreactivity-exaggerated response at normal to high levels of stimuli. (upward shift) |
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IL 4 in atopic patients can causes
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B cells to produce exaggerated amts of IgE ab directed against the allergen
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IgE ab bind to high affinity IgE receptors on mast cells, and crosslinking of the IgE receptors upon re-exposure to the allergen causes
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mast cell degranulaion
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IL-13 can cuse a type IV hypersensitivity rxn causing
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goblet cell hyperplasia
increased mucus production Smooth muscle hyperresponsiveness |
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Exposures to TB, viruses, siblings and day care w/in 6mo of life are associated with a _________ in incidence of asthma.
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decrease the incidence of asthma
(hygeine hypothesis) |
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Activated Th2 cells bind and activate B cells via, They also produce ____ and ____ which induce B cell transformation into IgE producing plasma cells.
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CD40 on the B cell surface
IL4 and IL13 |
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Two broad classes of pharma agents to treat asthma
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Relievers (bronchodilators) and Controllers (antiinflammatories)
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Relievers (bronchodilators) or Controllers (antiinflammatories)
Methylxanthines |
Both
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Relievers (bronchodilators) or Controllers (antiinflammatories)
Inhaled Corticosteroids, cromolyns, leukotriene pathway modifying agents |
Controllers (anti-inflammatories)
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Relievers (bronchodilators) or Controllers (antiinflammatories)
Ipratropium Tiotropium Epinephrine Isoproterenol Isoetharine Metaproternol Terbutaline Albuterol Levabuterol Pirbuerol Bitolterol Formoterol Salmeterol |
Relievers (bronchodilators)
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Relievers (bronchodilators) or Controllers (antiinflammatories)
Anticholinergics and Beta-adrenergic agonists |
Relievers (bronchodilators)
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Relievers (bronchodilators) or Controllers (antiinflammatories)
Ipratropium Tiotropium |
Relievers (bronchodilators)
Anticholinergics |
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Relievers (bronchodilators) or Controllers (antiinflammatories)
Epinephrine Isoproterenol Isoetharine Metaproternol Terbutaline Albuterol Levabuterol Pirbuerol Bitolterol Formoterol Salmeterol |
Relievers (bronchodilators)
beta adrenergic agonists |
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How do Anticholinergics work?
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antagonists at muscarinic receptors on airway sm muscle and glands leading to decrease bronchoconstriction.
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How do beta adrenergic agonists work?
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Agonists at beta adrenergic receptors on airway smooth muscle, act through a stimulatory G protien (Gs ie cAMP) to cause sm muscle relaxation and broncodilation.
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How do methylxanthines work?
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nonselective phosphodiesterase inhibitors the prevent the degredation of cAMP, and act as adenosine receptor antagonists; result is sm muscle relaxation and bronchodilation.
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How do inhaled corticosteroids work?
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Inhibit COX-2 action and prostiglandin biosynthesis by inducing lipocortins, activating endogenous anti-inflammatory pathways.
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How do cromolyns work?
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Inhibit chloride ion transport , which in turn affects calcium gating to prevent granule release, possibly decreasing mast cell response to inflammatory stimuli.
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Eosinophils are stimulated by ___ ___ and _______ produced by Th2 cells and mast cells
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IL3
IL5 GM-CSF |
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How are eosinophils recruited to the airway from the blood stream?
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Bind to adhesion molecules such as VCAM 1 and by following chemokine gradients.
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Once recruited to the airway, what do eosinophils do?
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Release lipid mediators, secrete cytotoxic granules, and release cytokines and chemokines to attract other inflammatory cells
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List five substances released by eosinophils
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Major Basic Protein
Eosinophilic cationic protein Eosinophil peroxidase Eosinophil derived neurotoxin Matrix metalloproteinases |
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Antigen Presenting Cells
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Macrophages
B cells Dendritic cells Eosinophils (pg 830 Golan) |
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What produces the following?
IL1 IL2 IL3 IL4 IL5 GM-CSF, TNFa, proteases, proteoglycans. When? |
Mast cells
4-6 hourse after exposure to allergen |
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What/Where are FcεRI receptors?
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High affinity IgE receptors on mast cells
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Preformed inflammatory mediators released from mast cells.
Mast cell degranulation acutely causes |
PAF, arachidonic acid, leukotriense, prostiglandin D2
Bronchoconstriction |
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SRS-A (slow reacting substances of anaphylaxis)
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Original name of leukotrienes.
Leukotrienes have a slower, but more powerful and sustained effect than that of preformed mediators. |
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_____________ __ is 1000x more potent than histamine in producing bronchoconstriction
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Leukotriene D4
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Anti-immunoglobulin E antibodies
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Omalizumab
(injections every 2-4 weeks, very costly, decreasing quantity of circulating IgE, affects both early and late phase asthmatic responses to challenge by inhaled allergen.) |
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Ipratropium bromide is derived from atropine but is less
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absorbed, leading to minimized adverse effects (nausea, dry mouth.)
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What type of adverse effect are found due to anticholinergic drugs (Ipratropium Br and Tiotropium)?
Type of drug? |
Mild effects
These drugs are both quaternary ammonium salts Competative antagonists at muscarinic acetylcholine receptors (M3) |
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Long acting anticholinergic recently approved for COPD treatment.
Why is it long acting? |
Tiotropium
Long acting because of its slow dissociation from M1 and M3 receptors. |
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Beta2 adrenergic stimulation of sm muscle leads to relaxation...so beta agonists....
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Bronchorelaxation...duh
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What epinephrine and where does it bind?
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Nonselective adrenergic agonist that binds to alpha, beta1 and beta2 receptors.
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Beta 1 receptors are also found in the heart, therefore, a side effect of epinephrine is...
Epinephrine causes________ via alpha receptors |
tachycardia, palpitations and potenial arrhythmias.
peripheral vasoconstriction leading to HTN |
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Slightly more selective than epinephrine, isoproterenol targets ____ ____ receptors, but ideally we'd like to target only _____.
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Beta 1 and 2
Beta 2 |
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Beta 2 adrenergic receptors, found in smooth muscle of the airway, are also found in _______ _______ _________ , so beta 2 drugs can cauase a tremor
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Peripheral skeletal muscle
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beta 2 selective beta adrenergic agonists bind to beta 2 adrenergic receptors 2-400x more strongly than beta 1 receptor. The consequence of this is:
List the 4 drugs |
significantly fewer cardiac events
Albuterol Terbutaline Pirbuterol Bitolterol |
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Peak effect of beta2 adrenergic agonists? Duration?
What two drugs can be used as long acting beta agonists? |
30-60 min
4-6 hours Formoterol Salmeterol |
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Two methylxanthines, theophylline & aminophylline, work via inhibition of phosphodiesterases III and IV via
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prevention of cAMP degredation (ie sm muscle relaxation, decreased intracellular Ca++, increased membrabe K+ conductance, and decreased myosin light chain kinase activity)
**They are bronchodilators and anti-inflammatory agents** |
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Adverse effects of theophylline:
Susceptible to what type of drug-drug interactions? |
Tachycardia, psychomotor agitation, gastric acid secretion, and diuresis.
With P450 inhibitors |
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Corticosteroids decrease the transcription of genes coding for many ....
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Proinflammatory proteins
(18!!! pg 834-835) |
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Corticosteroids reduce the # of inflammatory cells in the airway, and reduces hyperresponsiveness.
Inhibition of IL-4 and IL-5 markedly reduces the inflammatory response in asthma. Bc IL-4..... and IL-5..... |
IL-4 typically induces B cell production of IgE
IL-5 is typically an important recruiter of eosinophils |
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Why do the following corticosteroids have increased topical absorption?
Beclomethasone Triamcinolone Fluticasone Budesonide Flunisolide Mometsone Ciclesonide |
Substitution at the 17 alpha position increases topical absorption. (esp better if inhaled)
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Allergy antiinflammatory that is less efficacious but more safe than others:
(more effective in kids and young adults, prophylactic therapy in patients with allergic asthma associated with specific triggers) |
Cromolyns
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Disodium cromoglycate, and nedocromil are "mast-cell stabilizing agests"
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Cromolyns
(release of mediators of eos, neutros, monos, macros, and lymphocytes is also inhibited) |