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