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44 Cards in this Set
- Front
- Back
what is asthma?
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inflammatory disease - exaggerated Th2 response to an antigen that release cytokines to activate B cells and eosinophils!!!
B cells produce IgE to activate mast cells Eosinophils - in lung - make major basic proteins, leukotrienes and chemotactic factors ALL LEADS TO CHRONIC INFLAMMATION, BRONCHOSPASM, AND AIRWAY HYPERRESPONSIVENESS |
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what kinds of drugs do we use to treat asthma?
which is most effective |
anti inflammatory drugs - most effective b/c asthma is inflam condition
AND bronchodilators |
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what kinds of anti inflam drugs do we use for asthma? which is best
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corticosteroids - BEST b/c most versatile
leukotrienes modifiers mast cell stabilizers omalizumab |
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what is best way to take corticosteroids for asthma?
why |
inhale them. reduces side effects
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list the inhaled corticosteroids, and the top 2 we will see
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FLUTICASONE
BUDENSONIDE beclomethasone dipropionate triamcinolone flunisolide ciclesonide |
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MOA of inhaled corts on asthma
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they have anti inflam effect!!!
also... increase B adrenergic agents by enhancing cAMP production and upregulating receptor level - there is NO direct effect on muscle tension |
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when is steriod use NOT effective in asthma?
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during acute exacerbation
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side effects of inhaled corts
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bad taste - can lead to poor compliance
oral thrush - immunosuppressive dysphonia reflex cough and bronchospasm - due to hypersensitivity - so we give a Beta agonist before |
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what are the oral systemic corticosteroids
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prednisone
prednisolone methylprednisolone |
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when do we use oral systemic corticosteroids in asthma?
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in acute exacerbations - from 3-10days post to control severe inflammation(asthma)
only in LONG term for severe, difficult to control asthma and we minimize dose |
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what are the 2 mast cell stabilizers
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cromalyn
nedocromil |
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MOA of mast cell stabilizers
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Not extremely clear but prevents the degranulation of mast cels, and therefore stops release of mediators from mast cells
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difference between cromolyn and nedocromil
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nedocromil does same, but affects broader range of inflammatory cells
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would cromolyn or nedocromil reverse acute bronchospasm?
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no because damage has been done
Do NOT use for acute exacerbation of asthma |
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clinical uses of mast cell stabilizers
how is it given |
inhalation
It is an alternative agent for long term tx of mild persistent asthma preventative tx before exercise maximal therapeutic response within 2 weeks |
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side effects of mast cell stabilizers
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irritate throat - cough, transiet bronchospasm
Nedocromil has a bad taste |
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what are the leukotriene modifiers? and specific MOAs
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zileuton - inhibit LTE production
Montelukast zafirlukast - these 2 block LTE receptor |
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what are the effects of leukotrienes on the body
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activates the BLT receptor on leukocytes and causes chemotaxis
activates CytLT receptor on smooth muscles and causes bronchoconstriction, eosinophil migration, edema, secretion of viscous mucous |
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clinical uses of leukotriene modifiers in asthma??
how taken? how is it related to aspirin |
oral drugs
not for acute asthma alternative, not preferred tx, for mild persisten asthma adjunct therapy with inhaled corticosteroid use is aspirin sensitive asthmatics - due to COX inhibitor shift that increases LTE concentration |
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side effects of LTE modifiers
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churg-straus syndrome - seen in LTE receptor (cyt) inhibitors
elevated liver enzymes - zileuton |
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what is churg strauss sndrome
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one of many forms of vasculitis - inflam of vessels
independently associated iwth asthma or allergy occurs when px are withdrawn from corts while receiving LTRantagonist Angiitis in lungs, skin, nerves, abodmen Presentation: fever, wight loss, sinus inflammation in asthmatics, cough, SOB, numbness and weakness in extremities, seizures |
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What does omalizumab do?
how is it given why given |
Anti-IgE therapy
subQ injection every 2-4 weeks adjunct therapy for px's with allergies and SEVERE PERSISTENT astma that is inadequately controlled iwth combo of high dose corts and LABA |
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side effects of omalizumab
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anaphylaxis
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what are the classes of bronchodilators?
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Beta2 agonists
Muscarinic blockers methylxanthines |
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what are the main 2 beta2 agonists for asthma
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albuterol - SABA
salmeterol - LABA |
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anticholinergics we use for asthma
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ipratroprium bromide
tiotropium bromide - mainly COPD |
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what receptors do we see in the lungs
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B2 and M3 receptors
activating B2 blocking M3 |
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side effects of b2 agonists
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tremor
HYPOKALEMIA - b/c b2 receptors on sk. muscle, shifts k+ into cell palpitations sinus tachy Increase BP |
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what is the signaling pathway for B2 receptors that cause bronchodilation
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Gs - increase cAMP -> increase PKA -> phosphorylation of proteins
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what enzyme breaks down cAMP
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phosphodiesterase
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what are the 2 methylxanthines
what other compound are they similar to |
theophylline
aminophylline similar to caffeine |
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MOA of methylxanthines
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inhibit phosphodiesterase- keeps cAMP high from Beta2 receptor activation
and inhibits adenosine receptor |
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what is effect of methylxanthines on inflammatory cells? which type of cells?
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affects T-cells, eosinophils, and mast cells
prevents cAMP breakdown and blocks adenosine receptor to cause anti inflam effects |
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advantages and disadvantages of methylxanthines
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ad - oral, cheap
dis- narrow therapeutic index, erratic bioavailability, must monitor drug levels |
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methylxanthine side effects
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Gastric mucosa irritation - NVD, epigastric pain, cramps, anorexia
CNS simulation - headache, irritibility, restlesness, insomnia - worse in children! CV -palpitations, sinus tach, inc HR flushing, hypotension, ventricular arrythmias |
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what bronchodilators used for acute asthma attack
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SABA - drug of choice and drug for prevention of exercise induced asthma
ipratropium bromide - administered along with SABA in moderate or sever asthma exacerbations in ER!!!! |
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what bronchodilators used in Long term therapy of asthma
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LABA - adjunct to Cort therapy
maybe be used before exercise NOT recommended for monotherapy in long term tx!!!@$!@%! Theophylline - alternative but not preffered adunct to inhaled cort for long term control of moderate or persisten asthma |
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what drugs used for quick asthma relief
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SABA
anticholinergics - add on in ED systemic corts |
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what drugs used for long term asthma tx?
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1. anti inflams - corts, LTE mod, Mast cell stab, omalizumab
2. bronchodilators - LABAs and mehtylxanthine |
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what happens in COPD that we can control with drugs?
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Tissue damage
airway narrowing CHRONIC INFLAMMATION due to alveolar Macrophage and epithelial cell action due to smoking and irritants these activate neutrophils and CD8 lymphocytes |
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Why are corticosteroids not effective for COPD??
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Corts target mast cells and B- lymphocytes, and eosinophils which we see in Asthma
In COPD, we see lots of PMN infiltrate |
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bronchodilators in COPD for ACUTE exacerbation
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SABA
and anticholingeric if it doesnt work fast enough |
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Bronchodilators in COPD for chronic management
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as needed to prevent or reduce sx's
combo therapy generally LABA, tiotropium bromide, methylxanthines |
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Corticosteroids in COPD?
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ADD an inhaled glucocorticoid to bronchodilator tx for more sever symptomatic COPD (chronic tx)
systemi glucocorticoids for acute exacerbations of COPD - most sever |