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80 Cards in this Set
- Front
- Back
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what are the major hormone products of the adrenal gland cortex by zone?
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zona glomerulosa-aldosterone
zona fasiclata- cortisol zona reticulans- androgens |
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what is important about the enzyme systems in the adrenal gland?
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all three zones produce their hormones are created by the same enzymes so its impossible to focus inhibition of to any certain zone based on the enzyme.
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What is the hormone pathway for corticotropin releaseing hormone?
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CRH in the hyothalamus stimulates the release of ACTH by the pituitary.
ACTH stimulates the production of all three hormones from the adrenal gland. Cortisol and ACTH negatively feeds back to shut off CRH release. |
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what causes release of CRH?
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stress: emotional, physical, hypglycemic, cold exposure, pain.
circadian regulation also occurs. |
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what are the important enzymes in the adrenal gland pathways for production of aldosterone, cortisol, and androgens?
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3 beta hydroxysteroid dehydrogenase
17 alpha hydroxylase 21 hydroxylase 11 beta hydroxylase |
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what is the general MOA of steroids?
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work as transcription factors
bind to chaperone proteins mediate their effects by direct alteration of gene products This is why steroids with very similar chemical structure have such massively different effect in the body. |
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what are the glucocorticoids?
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cortisol
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what are the effects of cortisol on metabolism?
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stimulates hepatic glucose formation from glycerol/amino acids
increase storage of glucose as glycogen diminishes glucose utilization in periphery(catabolic) enhances protein catabolism in muscle and enhances lipolysis in fat. net result is to increase plasma gluose levels causes muscle wasting at high doses. |
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what is the main use of glucocorticoids (cortisol) as medication?
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antiinflammatory
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what are the antiinflammatory effects of glucocorticoids?
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inhibits the synthesis of leukotrienes, and prostaglandins
decrease cellular conten and release of histamine decrease the synthesis of interleukins and cytokines decrease the synthesis of MCF, MAF decrease activity of MIF decrease the release of lytic enzymes decrease the release of reactive O2 products. |
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what is the effect of IL-1, IL-2, IL-6 and TNF alpha on CRH and ACTH production
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stimulates production of CRH and ACTH, which leads to increased cortisol which decreases immune response leading to less of those products.
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What is the effect of aldosterone(mineral corticoids) on electrolyte and water balance?
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act on renal distal tubuels and collecting duct to increase Na reuptake(increase K and H excretion)
positive Na balance, increases extracellular fluid volume |
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what are the effects of high levels of mineral corticoids?
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increased blood pressure
hypokalemia, hypernatremia, and alkalosis |
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what are the effects of low levels of mineral corticoids?
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decreased blood pressure
hyperkalememia, hyponatremia, and acidosis. |
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What other system stimulates aldosterone release other than ACTH?
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renin angiotensin system
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what are the uses of synthetic adrenocorticosteroids?
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replacement therapy in primary deficiencies and gentic enzyem deficieencies
anti-inflammatory-cortisol(glucocorticoid) immunosuppressive therapy- cortisol, used mainly in allergies and asthma diagnostic purposes |
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what are the effects of prednisolone?
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4x the activity or glucocoticoid
with only .5 the effect of mineral corticoid. |
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what is the key difference btw prednisolone and cortisol?
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presence of a extra double bond
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what is the activity of cortisol?
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1x activity as a glucocorticoid
1x activity as a mineral corticoid |
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what is the activity of 9 alpha fluorocotisol?
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10x GCC
125x MCC |
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what is the activity of dexamethasone?
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30x GCC
0X MCC |
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what is the difference in structure of 9alpha flurorocotisol from cortisol?
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presence of a florine
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what is the difference btw dexamethasone and cortisol structurally?
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presence of florine and a extra double bond.and an extra methly group
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what are the three classes of cortisol derived drugs?
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cortisol like mixed function
delta double bond derivatives 6 and 9 alpha fluorinated/ 16 alpha or beta substituted prenisolones |
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what are the cortisol like mixed function drugs?
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9 alpha flurocortisol
cortisone corticosterone 11-deoxycorticosterone aldosterone cortisol |
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what are the main functions of the cortisol like mixed function drugs?
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all of them have either both GCC and MCC activity at equal or near equal levels or they are mainly MCC activity
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which of the mixed function drugs are mainly MCC function?
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aldosterone
11-deoxycorticosterone corticosterone 9 alpha flurocotisol |
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what are the delta double bond derative drugs?
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prenisolone
prednisone 6 alpha methylprednisolone. |
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what is the main action of the delta double bond derivative drugs?
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all have 4 to 5 x GCC activity with only 0.5 to 0.8x MCC activity
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what are the 6 and 9 alpha flouirinated, 16 alpha beta substited prednisolones drugs?
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paramethasone
triamcinolone dexamethasone betamethasone |
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what is the activity of the 6 and 9 alphal flurinated 16 alpha beta substied predinolones?
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all have 5-25x GCC with 0x MCC
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what is addisons disease?
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primary adrenal insufficinecy
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how is addisons disease treated?
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replacement therapy with cortisol
30-40mg of cortisol (2/3 given in am and 1/3 given late afternoon) cortisol usually supplies suffiecient glucocorticoid and mineralcorticoid activity but if additional MCC is needed fludrocotisone is usually given |
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what is used in addisons if cortisol alone is not providing enough MCC activity?
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fludrocotisone
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what can occur that requires dose adjustment with cortisol in addisons disease?
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illness or stress requires dose adjustment up to 2-3 timex nomral dose.
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What is the most common ezyme deficiency associated with cortisol levels?
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21 hydroxylase defeiency
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why is cortisol level often normal in 21 hydroxylase deficiency and what is the implication of this?
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decreased cortisol leads to increased ACTH production until cortisol is high enough to produce inhibition. This causes adrenal hyperplasia and overproduction of all the products that dont require 21 hydroxylase.
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what is elevated in 21 hyroxylase deficiency?
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DEHP(androgen)
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What is the treatment for 21 hydroxylase deficiency?
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100mg/day of cortisol for 5days then reduced to replacemnt therapy levels.
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what are the early levels in 21 hydroxylase deficiency?
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low cortisol
low aldosterone slightly high DEHP |
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what are the late levels in 21 hydroxylase deficiency?
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normal cortisol an aldosterone
super high DHEA |
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what important enzymes are required for aldosterone and cortisol production?
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11 beta hydroxylase
21 hydroxylase |
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what enzymes are imorpontant and required for DHEA production
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17alpha hydroxylase
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what is the major symptom of 21 hydroxylase deficiency?
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masclinization
not low cortisol or aldosterone effects bc of the eventual adrenal hypertrophy |
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what are the toxic effects of GCC steroids?
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CNS effects drugs may produce euphoria
steroid diabetes-prediabetic may exhibit signs of clinical diabetes skeletal effects- osteoporosis bc steroid decrease Ca absorption which leads to increased PTH stimulation of bone resorption. increased infectivity- pt may need prophylacitc antibiotics ulcers- may play a permisive role in ulcer developement(dont cause just make it easier for them to develop) delayed wound healing adrenal atrophy |
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what is the problem with adrenal atrophy and steroid use?
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adrenal atrophy may start after only 1 week of therapy
adrenal atrophy leads to impaired reactions to stress |
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how are patients treated for adrenal atrophy from steroid use?
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slowly titrated off of the steroids
recover from adrenal atrophy long term if > 30mg/d for >4 weeks or > 80mg/d for >2 weeks there could be atrophy for over a year with needed supplimental GCC. |
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How is adrenal atrophy prevented?
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given acutely not long term
pt switch to alternate day dosing if possible with double daily dose if dose is given like this adrenals do not atrophy stress repnse remains nomral and other side effets are decreased. |
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what is cushing syndrome?
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results from pituitary gland secreting excess ACTH(pituitary adeonma=true cushing disease not syndrome),
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what is the renin angiotensin aldosterone system?
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i. R-A-A system: decreased blood volume increased renin secretion conversion of angiotensinogen to angiotensin I angiotensin I is converted to angiotensin II by angiotensin-convering enzyme (ACE)
ii. Angiotensin II acts on the zona glomerulosa of the adrenal cortex to increase synthesis of aldosterone. |
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what occurs in fat mobilization from cortisol?
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fat accumulation at the trunk
stress raises cortisol cortisol increases belly fat!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! |
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what is the main cause of addisons disease?
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autoimmune 70-80%
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what is the dexamethasone suppression test?
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low dose dex turns off ACTH in normal pt
4x hither needed to turn off true cushing disease if that is still not enough then you suspect cancer. |
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what is petrosal sinus testing?
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blood sample from viens that directly drain pituitaries
CRH given and ACTH levels are measrued compared with peripheral veinous blood. if ACTH elevated due to cushings then petrosal will be higher than peripheral if its due to peripheral tumor then it will be higher in the periphery. |
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what is cushign syndrome symptoms?
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cotisol excess
truncal obesity buffalo hump muscle wastin steroid diabetes bone demineralization growth retardatin CNS Hypertension delayed wound healing hypokalemic alkalosis hirsutism amenorrhea |
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how is cushing disease treated?nonpharm
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removal of pituitary adenoma-surgical ressection or radiatino
exctopic acteh syndrome treated with aggressive ablation therapy adrenl tumors- treated with adrenalextomy |
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how is cushing treated with drugs?
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o,p-DDD(mitotane)
-aminoglutethimide -metyrapone |
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what is probelm with pharm treatment of cushing?
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pharm treatments focus on blocking cortisol production
however the problem is usually excess ACTH production cortisol inhibits ACTH production so blocking cortisol actually increases ACTH production This will lead to eventual hyperplasia and overcoming of the drugs to bring back the hypercortisol levels also ACTH stims mineralcorticoids as well so super high ACTH during this treatement leads to increased androgen and MCC productions so pharm treatment is only good as a temporary bridge till cause of cushing is established and fixed. |
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what is mitotane devrieve from?
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DDT
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what is the MOA of Mitotane?
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reacts with cytochrome P-450 compenets of hyroxylase reactions in 21, 17alpha, and 11beta hydrozylases
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what area does mitotane target?
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specific for reticulans and fasciculata
so there is less effect on MCC in the cortex |
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what is an advantage to mitotane?(and also a disadvanatage)
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ACTH does not overcome drug effects
because it destroys the tissue, this toxicity has led to it being removed fro US market. |
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What is amphenone B derived from?
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DDT as well
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What is difference btw amphenone B and mitotane?
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amphenone is more potent
does not destroy tissue ACTH secretion can overcome it and leads to gland hypertorphoy |
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what is use of amphenone B
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not used was also removed from US market due to toxicity
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What is MOA of metyrapone?
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specific inhibitor of 11beta hydroxylase
blocks conversion of 11-deoxycortisol to cortisol |
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what is the use of metyrapone?
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rarely used due to side effects
but not so toxic as others so its still on the market sometimes its used if cortisol is high for unknown cause can be used to test pituitary reserve of ACTH by decreasing cortisol and seeing how high ACTH gets. |
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which of the DDT derived drugs is still on the market?
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metyrapone
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what is MOA of aminoglutethimide?
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inhibits an early step in steroid synthesis
cholesterol to pregnenolone this reduces secretion of all of them: MCC, GCC, and androgens not specific to andrenals |
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what are the downsides to aminoglutehimide?
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not specific to adrenals
effects are overcome by ACTH |
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what are the uses of aminoglutethimide?
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used primarliy for cusshings syndromes that are due to secondary adrenal cancers
also used with dexamethasone to decrease androgen secretion. |
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what is the MOA of ketoconazole
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blocks many steroid synthesis P450s
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what is a problem with ketoconazole?
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causes compensaotry increase in ACTH and as a result androgens and aldosterone increase as well.
also displaces estrogen and testosterone from binding protiens which increases the estrogen/testosterone ratio can cause gynecomastia an doligospermia in males while altering menstrual cycles in females. |
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what is the MOA of Mifepristone-RU486?
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GCC receptor antagonists
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what is the MOA of spironolactone?
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MCC receptor antagonists
acts to treat excessive alderstone secretion used as Ksparing diruetic |
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What are the effects of ACE inhibitors on the steroid system?
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ACE inbhitors decrease acivity of the renin angiotensin system which moderates aldosterone release.
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what is a common presenatino of young male who is exposed to insecticde that inhibits 21 hydroxlase?
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mustache
cortisol and aldosterone normal due to compensation of elevated ACTH hyperplasia but a lot of activiy is shunted to androgen production so there will be increased masculinization of the boy who is still prepubescent. |
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what are the important precursors to the aldosterone?
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cholesterol
pregnenonlone prednisone 11deoxycorticosterone aldosterone |
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what are the important precursors to cortisol?
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cholesterol
prenenolone 17OH pregnenolone 11 deoxycortisol cortisol |
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what are the important precursors to estradiol?
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cholesterol
pregnenolone 17OHpregnenolone DHEA androstenedione testosterone estradiol |
