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44 Cards in this Set

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what is asthma?
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
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
what kinds of anti inflam drugs do we use for asthma? which is best
corticosteroids - BEST b/c most versatile
leukotrienes modifiers
mast cell stabilizers
omalizumab
what is best way to take corticosteroids for asthma?
why
inhale them. reduces side effects
list the inhaled corticosteroids, and the top 2 we will see
FLUTICASONE
BUDENSONIDE
beclomethasone dipropionate
triamcinolone
flunisolide
ciclesonide
MOA of inhaled corts on asthma
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
when is steriod use NOT effective in asthma?
during acute exacerbation
side effects of inhaled corts
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
what are the oral systemic corticosteroids
prednisone
prednisolone
methylprednisolone
when do we use oral systemic corticosteroids in asthma?
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
what are the 2 mast cell stabilizers
cromalyn
nedocromil
MOA of mast cell stabilizers
Not extremely clear but prevents the degranulation of mast cels, and therefore stops release of mediators from mast cells
difference between cromolyn and nedocromil
nedocromil does same, but affects broader range of inflammatory cells
would cromolyn or nedocromil reverse acute bronchospasm?
no because damage has been done
Do NOT use for acute exacerbation of asthma
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
side effects of mast cell stabilizers
irritate throat - cough, transiet bronchospasm

Nedocromil has a bad taste
what are the leukotriene modifiers? and specific MOAs
zileuton - inhibit LTE production
Montelukast
zafirlukast - these 2 block LTE receptor
what are the effects of leukotrienes on the body
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
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
side effects of LTE modifiers
churg-straus syndrome - seen in LTE receptor (cyt) inhibitors

elevated liver enzymes - zileuton
what is churg strauss sndrome
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
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
side effects of omalizumab
anaphylaxis
what are the classes of bronchodilators?
Beta2 agonists
Muscarinic blockers
methylxanthines
what are the main 2 beta2 agonists for asthma
albuterol - SABA
salmeterol - LABA
anticholinergics we use for asthma
ipratroprium bromide
tiotropium bromide - mainly COPD
what receptors do we see in the lungs
B2 and M3 receptors
activating B2
blocking M3
side effects of b2 agonists
tremor
HYPOKALEMIA - b/c b2 receptors on sk. muscle, shifts k+ into cell
palpitations
sinus tachy
Increase BP
what is the signaling pathway for B2 receptors that cause bronchodilation
Gs - increase cAMP -> increase PKA -> phosphorylation of proteins
what enzyme breaks down cAMP
phosphodiesterase
what are the 2 methylxanthines

what other compound are they similar to
theophylline
aminophylline

similar to caffeine
MOA of methylxanthines
inhibit phosphodiesterase- keeps cAMP high from Beta2 receptor activation

and
inhibits adenosine receptor
what is effect of methylxanthines on inflammatory cells? which type of cells?
affects T-cells, eosinophils, and mast cells

prevents cAMP breakdown and blocks adenosine receptor to cause anti inflam effects
advantages and disadvantages of methylxanthines
ad - oral, cheap
dis- narrow therapeutic index, erratic bioavailability, must monitor drug levels
methylxanthine side effects
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
what bronchodilators used for acute asthma attack
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!!!!
what bronchodilators used in Long term therapy of asthma
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
what drugs used for quick asthma relief
SABA
anticholinergics - add on in ED
systemic corts
what drugs used for long term asthma tx?
1. anti inflams - corts, LTE mod, Mast cell stab, omalizumab
2. bronchodilators - LABAs and mehtylxanthine
what happens in COPD that we can control with drugs?
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
Why are corticosteroids not effective for COPD??
Corts target mast cells and B- lymphocytes, and eosinophils which we see in Asthma

In COPD, we see lots of PMN infiltrate
bronchodilators in COPD for ACUTE exacerbation
SABA
and anticholingeric if it doesnt work fast enough
Bronchodilators in COPD for chronic management
as needed to prevent or reduce sx's
combo therapy

generally LABA, tiotropium bromide, methylxanthines
Corticosteroids in COPD?
ADD an inhaled glucocorticoid to bronchodilator tx for more sever symptomatic COPD (chronic tx)

systemi glucocorticoids for acute exacerbations of COPD - most sever