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69 Cards in this Set

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what is the main feedback signmal in the HPA axis?
cortisol
when can the HPA feedback mechanism be overcome?
stress
where is cortisol synthesized?
zona fasciculata
where is cortisol metabolized?
the liver
what structural component of cortisol is required for cortisol activity?
ketone group and double bond at C4-5
how does 90% of cortisol travel through the body?
bound to corticosteroid binding globulin
what form of cortisol is active?
free
what happens in hyperthyroidism?
there is an increase in CBG thus a decrease of effective cortisol
what is dexamethasone?
a 9 alpha-fluouro analog
what is betamethasone?
9 alpha-fluoro analog
what is is triamcinolone?
9 alpha-fluoro analog
how do 9 alpha-fluoro analogs travel through the body?
primarily bound to albumin
what is the overall effect of cortisol on carbohydrates and protein?
increase in blood glucose and protein breakdown
what is the overall effect of cortisol on lipids?
overall redistribution of body fat from extremities to central regions
where will fat be deposited with high levels of cortisol?
decreased in extremities
increased in back of neck and face
what effect do cotricosteroids have on electrolyte and water balance?
retention of Na+ and increased extracellular fluid volume
increased excretion of K+ and H+
which steroid is the retention of Na+ and excretion of K+ and H+ mainly due to?
mineralcorticoid
what will an excess of corticosteroids do to the cardiovascular syste?
hypertension
what are cardiovascular changes from corticosteroids mostly due to?
secondary to mineralcorticoid induced changes
what will an excess of corticosteroids do to mood?
mood elevation
what will a deficiency of corticosteroids do to mood?
apathy, depression
what does excess of corticosteroids do to bones?
overall osteoporosis
how do corticosteroids increase bone breakdown?
increased osteoclast formation via
altering Ca++ homeostasis and vitamin D
what should chronic glucocorticoids use include to prevent osteoporosis?
bisphosphates
what do glucocoticoids do to the immune system?
inhibition of proliferation, activation, and chemotaxis of multiple luekocytes
how do glucocorticoids decrease immune response? (3)
decreased transcription/translation of proinflammatory mediators
increased transcription/translation of anti-inflammatory mediators
where are mineralcorticoids synthesized?
zona glomerulosa
what is mineralcorticoid mainly regulated by?
activation of agtII receptors
how much are oral glucocorticoids affected by first pass metabolism?
not signiticantly
how long do short acting oral glucocorticoids last?
8-12hrs
how long to intermediate acting oral glucocorticoids last?
18-36hrs
how long to long acting oral glucocorticoids last?
36-54hrs
what is a short acting oral glucocorticoid?
hydrocortisone
what patients should you be careful administering hydrocortisone to and why?
hypertensive patients because hydrocortisone includes equal parts mineralcorticoid and glucocorticoid
what are 3 intermediate acting oral glucocorticoids?
prednisone
prednisolone
methylprednisolone
what is a long acting oral glucocorticoid?
dexamethasone
what 3 things is potency a function of in topical glucocorticoids?
intrinsic activity of the drug
concentration in the formula
vehicle in the formultation (alcohol, lotion, etc)
what 2 glucocorticoids cannot be used topically and why?
cortisone and prednisone because they have a ketone on carbon 11 which is normally removed by 11-beta-hydroxysteroid dehydrogenase converts this into a hydroxyl group when taken orally
where are glucocorticoid receptors found?
in all tissues of the body
where are mineralcorticoid receptors found? (3)
kidney
colon
sweat glands
what affinity does cortisol have for glucocorticoid receptors vs mineralcorticoid receptors?
equal affinity
how are actions of glucocorticoids minimized in mineralcorticoid receptor expressing tissues?
11-beta-hydroxysteroid dehydrogenase type 2 reaction which converts cortisol to cortisone and deactivates it
what is the type I mechanism of glucocorticoid signal transduction?
direct
binds to receptor, receptor dissociates from heat shock proteins and crosses the nuclear membrane to effect its actions
what is the type II mechanism of glucocorticoid signal transduction?
indirect
GC/GR complex binds to DNA transcription factors (eg protein 1 or kappa-B)
what does the decrease of NF-kappa beta in turn decrease? (2)
PLA-2 trancription
GM-CSF transcription
how do glucocorticoids decreased prostaglandin and leukotriene synthesis?
decreases NK-kappa-beta which decreases PLA2
how do glucocorticoids decreased chemotaxis of all leukocytes? (2)
impairs TNF-alpha signaling
decreases IL-1 transcription
how do glucocorticoids decrease T cell synthesis and activation as vell as B-cell, monocyte, and NK cell activity?
decreases IL-2 transcription (growth factor)
name 4 cytokines that glucocorticoids decrease trancription of
GM-CSF
IL-6
TNF-alpha
IL-10
what is an important transcription factor for cellular growth and proliferation?
AP-1
whose activity is decreased by glucocorticoids?
AP-1
what 2 adenomas can cause endogenous overproduction of glucocorticoids?
pituitary adenomas
adrenal adenomas
what is primary adrenal insufficiency?
addisons disease
what can secondary adrenal insufficiency be due to?
defective anterior pituitary or hypothalamic function
what can atrophy due to adrenal insufficiency thus impairing recovery? (2)
anterior pituitary
hypothalamus
what do these symptoms suggest in terms of adrenal insufficiency?
GI symptoms
dehydration
hypothalamus
hyperkalemia
weakness
it was due to a sudden withdrawal of steroids
what can also cause symptoms of adrenal insufficiency and therefore warrants an increase in glucocorticoid dose?
stress
how long may it take for the adrenal glands to fully recover from insuffieicnecy?
2-18 months
what are 3 glucocorticoid complications that are unavoidable in early therapy?
insomnia
increased appetite
weight gain
what are 4 glucocorticoid complications that are common in patients with underlying risk factors?
hypertensions
diabetes
peptic ulcer disease
glaucoma
what are 2 glucocorticoid complications that are delayed and insideous?
cataracts
atherosclerosis
how do you diagnose cushings? (2 step process)
dexamethasone is administered overnight
level of cortisol is measures to diagnose cause of cortisol production
what are 4 conditions most treated with corticosteroids?
IBD
asthma
eczema
psoriasis
what corticosteroid is most used for IBD and severe asthma?
prednisolone
what corticosteroid is already active when administered?
prednisolone
what glucocorticoid is used for asthma
beclomethasone/budesonide
what glucocorticoid is used for graft-vs-host disease?
methylprednisone
what glucocorticoid is used for crohns
triamcinolone acetonide
how can glucocorticoids be used in developing fetus?
stimulation of lung maturation
admin 48 hours prior to birth and 24 hours prior to birth