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79 Cards in this Set
- Front
- Back
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what does the hypothalamus govern?
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emotional responses, autonomic functions and hormone synthesis
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what hormone is released by the anterior pituitary due to the release of CRH from the hypothalamus?
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Adrenocorticotropin Hormone (ACTH)
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what hormone is release by the adrenal gland d/t the release of CRH from the hypothalamus?
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cortisol
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what pathway and organ control ACTH release?
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hypothalamus and negative feedback
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what is another name for CRH?
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CRF- corticotrophin releasing factor
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what can overcome feedback inhibition by cortisol to increase the levels of secreted cortisol?
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stress (d/t hypolglycemia, trauma, hemorrhage, cold, etc)
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what effect does negative feedback by cortisol cause the anterior pituitary and hypothalamus?
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anterior pituitary:
decreased ACTH secretion decreased response of pituitary to CRH hypothalamus: decreased release of CRH |
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hormones synthesized and secreted by the cortex of the adrenal gland follow a certain rhythm, what is it? Name these hormones
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circadian rhythm--> peak early morning and after meals.
glucocorticoids- cortisol mineralocorticoids- aldosterone |
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what hormone is synthesized in the zona fasciculata of the adrenal cortex? It impacts regulation and function of which processes?
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glucocorticoids- cortisol
-metabolism -stress response -CNS fxns -immunity |
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what hormone is synthesized in the zona glomerulosa of the adrenal cortex? It impacts regulation of what?
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Mineralocorticoids- aldosterone
-Na+ and K+ concentrations in extracellular fluids (Low K+, High Na+) |
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what primarily regulates mineralocorticoid secretion?
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activation of angiotensin II receptors
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which one (mineralocorticoids or glucocorticoids) is more responsive to ACTH?
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glucocorticoids
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what is produced in the adrenal cortex that causes masculinization?
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androgens- dehydroepiandrosterone (DHEA)
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where is cortisol metabolized?
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liver
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2 double bonds are reduced and one ketone is converted to a hydrogxyl during the metabolism of cortisol, where are these located?
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double bonds- C4,5
ketone- C3 |
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what is cortisol conjugated with prior to excretion by kidneys?
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sulfate and glucoronate
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what percentage of cortisol is freely circulating? what are the rest of the cortisol molecules bound to?
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5-10%; Corticosteroid-binding globulin (CBG)
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what type of disorder will increase CBG production?
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hypermetabolic conditions (like hyperthyroidism)
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where can fluorine be introduced into the structure of cortisol to increase its activity? what do these molecules primarily bound to? what are the three drugs that fall into this category?
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9 alpha position.
Primarily bound to albumin. dexamethasone, betamethason, triamcinolone. |
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what are the oral glucocorticoids? Place them in their appropriate category: short-acting, intermediate-acting, and long-acting?
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short-acting (8-12): hydrocortisone
intermediate-acting (18-36): pednisone, prednisolone, methylprednisolone Long-acting (36-54): dexamethasone |
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what two glucocorticoids cannot be used topically?
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cortisone and pednisone
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what effects do corticosteroids have on the metabolism of carbohydrates/ proteins? what does this culminate in?
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Increase hepatic gluconeogenesis
increase formation of glycogen in the liver increased protein breakdown into AA decreased glucose utilization. ---> increase in blood glucose. |
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what are carbohydrates/ protein also referred to as?
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the anti-insulin
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what effects do corticosteroids have on the metabolism of lipids? what does this culminate in?
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net increased lipolysis --> increase FFA
increased deposition of fat in back of neck and face (moonface) decreased deposition of fat in extremities --> redistribution of body fat from extremities to central regions (lateral to medial) |
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what part of the nephrons do corticosteroids affect? why?
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distal tubule and collecting ducts to enhance reabsorption of Na from tubular fluids
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Corticosteroids cause the excretion of ___ and ____.
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K+ and H+
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which type of corticoid is most responsible for the effect on the nephrons?
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mineralcorticoid activity
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T/F
Most effects seen in the cardiovascular system are secondary to mineralocorticoid induced changes in renal Na+ excretion. |
True
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what does an excess of corticosteroid cause?
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HTN, arteriosclerosis, cardiomyopath and enhanced vascular responsiveness to vasoconstrictors such as NE and angiotensin
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what does a deficiency in corticosteroid cause?
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Hypotension, unresponsiveness to vasoconstrictors
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what effect does excess CS have on the CNS? deficiency? which CS is truly to blame?
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excess- mood elevation, euphoria, insomnia, motor activity
deficiency- apathy, depression irritability, psychosis CS to blame --> mineralcorticoid activity |
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what affects do CS's have on bone? what is the overall affect?
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decreased osteoblast formation and activity
increased osteoclast formation overall--> osteoporosis |
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what type of corticosteroids are used for anti-inflammatory and immunosuppressive effects?
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glucocorticoids
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what are the general effects of glucocorticoids on the immune system? what are the overall effects?
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-decreased transcription/ translation pro-inflammatory mediators
-decreased production of Prostaglandins and Leukocytes. -increased transcription/ translation of anti-inflammatory factors --> proliferation, activation and chemotaxis of multiple Leukocytes are impaired by glucocorticoids. |
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what are the two corticoid receptor genes? where are they located?
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1) GC- glucocorticoid receptor (GCR)
* widely distributed throughout the body 2) MC- mineralocorticoid receptor (MCR) * tissue distribution limited to the kidney (distal tubule, collecting ducts), colon sweat glands |
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what hormone has equal affinity for both GC and MC receptor?
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Cortisol
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what is the glucocorticoid receptor normally bound to when not activated?
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heat shock proteins 70 and 90
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where does the GR/S homodimer bind to? what happens when they do bind?
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directly to DNA in specialized regions referred to as Glucocorticoid response elements (GRE).
once they bind- it alters transcription rates of DNA into mRNA which alters mRNA translation into protein and alters level of mediators of inflammation. |
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what region of the steroid hormone DNA binding protein is responsible for altering the transcription rate of DNA?
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trans-activation region located at the amino-terminal end of the protein molecule.
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what are "zinc fingers"?
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the amino acid sequence of the DNA binding region of the Glucocorticoid receptor protein
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What can S/GR complexes bind to in a type II mechanism of action
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DNA trascription factors like AP-1 or NFkB
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how do glucocorticoids inhibit the effects of NFkB indirectly? directly?
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indirectly: S/GR complex binds to the transcription factor NFkB and acts as an antagonist
directly: S/GR complex binds directly to DNA, increases transcription rates for IkBalpha which prevent NF-kB activity. |
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what effect do glucocorticoids have on NFkB as far as prostaglandin synthesis is concerned?
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- decreases PG synthesis d/t 2 things: decreased transcription of COX-2 and decreased transcription of PLA2 which decreases released arachidonic acid leading to a decrease in cyclooxygenase and lipoxygenase enzymes --> decreased PG synthesis
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what effect do glucocorticoids have on NFkB as far as leukotriene synthesis is concerned?
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- decreased transcription PLA2 --> decreased release of arachidonic acid --> decreases substrate for COX and lipo --> decrease leukotriene synthesis
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what effect do glucocorticoids have on NFkB as far as transcription of GM-CSF is concerned?
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decreased transcription of cytokine GM-CSF
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what effect do glucocorticoids have on NFkB as far as TNF alpha signaling is concerned?
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its impaired since NFkB is an intracellular 2nd messenger for TNF. Leading to a decrease in overall chemotaxis of all leukocytes.
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what effect do glucocorticoids have on NFkB as far as IL-1 transcription is concerned?
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decreases it--> decreased chemotaxis of all leukocytes
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what effect do glucocorticoids have on NFkB as far as T-lymphocyte synthesis and activation is concerned?
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decreased T-lymphocytes because of a decreased IL-2 transcription (T cell growth factor)
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what effect do glucocorticoids have on NFkB as far as the innate immunity is concerned?
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decreased d/t decrease in IL-2 transcription
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what effect do glucocorticoids have on NFkB as far as IL-6 transcription is concerned?
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decreased IL-6 transcription
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what effect do glucocorticoids have on NFkB as far as GM-CSF transcription is concerned?
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decreased
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what effect do glucocorticoids have on NFkB as far as TNF-alpha transcription is concerned?
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decreased
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what effect do glucocorticoids have on NFkB as far as IL-10 transcription is concerned?
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increased
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what effect do glucocorticoids have on NFkB as far as AP-1 activity is concerned?
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decreased
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which actions are mediated via direct mechanism?
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IL-10, IL-6, IL-2, IL-1 transcription, TNF-alpha transcription, GM-CSF transcription
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what activities of glucocorticoids are mediated via indirect mechanisms?
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AP-1
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what is iatrogenic cushings?
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exogenous administration of glucocorticoids
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what are the two causes of hypercortisolism?
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iatrogenic cushings and endogenous overproduction that is not responsive (or less responsive) to feedback inhibition by glucocorticoids.
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what are the sxs associated with cushing's syndrome?
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weight gain (incr appetite)
muscle weakness excess hair growth hair loss fat redistribution HTN osteoporosis infection gonadal dysfunction |
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which of the sxs associated with cushing's syndrome is due to mineralcorticoids or androgen effects?
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excess hair growth
hair loss HTN gonadal dysfunction |
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what is addison's disease?
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primary adrenal insufficiency due to defective adrenal function
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what is secondary adrenal insufficiency due to?
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defective anterior pituitary or hypothalamic fxn
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what is a common cause of secondary adrenal insufficiency?
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exogenous corticosteroid administration
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what may result in acute adrenal insufficiency?
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sudden withdrawal of steroids after prolonged therapy
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how long does recovery of full adrenal fxn take?
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2-18 months
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how is acute adrenal insufficiency characterized by?
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GI symptoms (N/V, pain), dehydration, hyponatremia, hyperkalemia, weakness and hypotension
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what do you give someone with addison's disease?
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hydrocortisone-- 2/3s in the morning, 1/3 in the afternoon.
some may need mineralcorticoid replacement--> fludrocortisone which is a potent mineralcorticoid |
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how do you tx secondary or tertiary adrenocortical insufficiency?
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hydrocortisone dosed just like addison's dz. Usually do not require mineralocorticoid replacement
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what drug to you use to diagnose cushing's syndrome?
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dexamethasone
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what is the drug of choice for systemic/ oral tx of inflammation like IBD and severe asthma?
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prednisolone
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what is/are the drug (s) of choice for immunosuppression such as in graft vs host?
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methylprednisolone or dexamthasone
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what is/are the DOC (s) for inhalation therapy such as asthma?
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beclomethasone and budesonide
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what is/are the DOC (s) for allergic rhibitis?
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fluticasone
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what is/are the DOC (s) for severe psoriasis, eczema, distal UC or crohn's?
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triamcinolone acetonide - severe psoriasis
hydrocortisone- eczema, distal UC or Crohn's. |
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what three drugs are used for the tx of allergies? how quickly are they metabolized?
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beclomethassone dipropionate, budesonide, fluticasone.
poor bioavailability and are rapidly metabolized. |
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what glucocorticoid do you use for stimulation of lung maturation in the fetus? when is it administered?
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bethamethasone- 48 hours prior to birth and then 24 hours prior to birth
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what is used to tx cushing's syndrome associated with adrenal carcinoma and ectopic ACTH producing tumors? what does it do?
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Mifepristone- antagonist at the GC and progestin receptors
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How do you tx hyperladosteronism? what does it do?
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spironolactone- antagonist at the MC receptor
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what are some common SE in association w/ corticosteroids w/ pts who have underlying risk factors?
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HTN, diabetes mellitus, peptic ulcer dz, glaucoma.
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