Term
|
Definition
| hypothalamic pituitary axis |
|
|
Term
| what does it mean when said HPA is dinural |
|
Definition
| higher activity in morning |
|
|
Term
| what can increase the HPA axis activity the best |
|
Definition
| stress, which can over ride normal feedback controls |
|
|
Term
| what does ACTH stand for, what is its job |
|
Definition
adrenocorticotrophic hormones
stimylates adrenal cortex to secrete glucocorticoids, mineralcoricoids, weak androgens |
|
|
Term
| what are two weak androgens |
|
Definition
andeostendione
dehydropiandrosteone |
|
|
Term
| what are the three zones of the adrenal cortex |
|
Definition
zona glomerulosa - outer
zona fasculata - inner
zona reticularis - inner |
|
|
Term
| what enzymes does cortex outer zone have, what does it secrete |
|
Definition
| secretes aldosterone (mineralcorticoids) via aldosterone synthase |
|
|
Term
| how is mineralcorticoid production stimulated |
|
Definition
ACTH acutely stimulates
angiotensin II receptors with Gs protein initiate it |
|
|
Term
| what happens to the cortex if it does not get enough stimulation |
|
Definition
| does not atrophy without pituitary stimulation |
|
|
Term
| what enzymes does the cortex inner zones have, what do they secrete |
|
Definition
12-a-hydroxylase, 11-B0hydroxylase
secretes glyucocorticoids |
|
|
Term
| what stimulates inner cortex, what if there is too much stimulation |
|
Definition
| increases in ACTH cause hyperplasia, hypertrophy, increased cortisol and androgens |
|
|
Term
|
Definition
| ACTH increases due to impaired cortisol synthesis |
|
|
Term
| what happens if the inner cortex does not get stimulation |
|
Definition
|
|
Term
| what occurs in the acute phase of steroid production |
|
Definition
| within seconds increased supply of cholesterol to substrate (depends on amount of cholesterol) |
|
|
Term
| what occurs in the chronic phase of steroid production |
|
Definition
| within hours steridogenic enzyme transcription is increased |
|
|
Term
| where are most of the enzymes for steroid production |
|
Definition
|
|
Term
| explain the process of steroid hormone production (3 steps) |
|
Definition
1. cholesterol is turned into pregnilone via CHOLESTEROL SIDE CHAIN CLEVAGE ENZYME (P450 SCC) **RATE LIMIT
2. pregnilone is turned into cortisol, aldosterone, and adrenal androgens
3. products go to receptors and cause transcription. their structures are similar and they can activate e/o receptors |
|
|
Term
| how is production of cortisol stimulated |
|
Definition
| hypothalamus releases CRF and AVP which activate pituitary which releases ACTH which acrivates adrenal gland which releases cortisol |
|
|
Term
| what controls rate of cortisol production |
|
Definition
| ACTH release from pituitary corticotropes which are regulated by corticotropin releasing hormone (CRH) |
|
|
Term
| how is cortisol production/stimulation regulated (2) |
|
Definition
ACTH can stimulate production but will burn out so it stops activity in hypothalamus
cortisol (glucocorticoids) stop activity in pituitary and hypothalamus |
|
|
Term
| cortisol and aldosterone bind same receptors for same affinity, how does the body discriminate |
|
Definition
| in mineralcorticoid (ALD) receptors it has enzyme barrier with 11-B-hydroxy DH that metabolizes cortisol to cortisone which cannot bind ALD receptor |
|
|
Term
| what are the 7 areas / systems that corticosteroids effects |
|
Definition
carb and protein metabolism
lipid metabolism
cardiovascular
skeletal muscle
CNS
blood
immune supression/anti-inflammatory |
|
|
Term
| what do corticosteroids do to carb and protein metabolism |
|
Definition
protect glucose dependent tissues from starvation (brain and heart)
glucogenolysis
glyconeogenesis
diminish glucose utilization in tissue
cause protein break down |
|
|
Term
| what do corticosteroids to to lipid metabolism |
|
Definition
stimulate lipolysos
increase fat in neck (buffalo hump) and face (moon faces)
loss of fat in extremities |
|
|
Term
| what do corticosteroids to do skeletal muscle |
|
Definition
needed for normal function
decreased muscle work due to adrenocorticol insufficiency (addison's disease)
hypercorticism: causes muscle wasting |
|
|
Term
| what effects do corticosteroids have on CNS (5) |
|
Definition
mood, behavior, brain excitability
in cushings and addisons: neuroses, psychoses |
|
|
Term
| what does corticosteroids do to the immune system (7) |
|
Definition
decreases cytokine production, lymphocyte response, histamines, leukotrienes, arachadonic acid release via phospholipase A2 inhibition
supress inflammation
decrease WBC circulation |
|
|
Term
| what are the HPA axis drugs (2) |
|
Definition
|
|
Term
| what are the short acting glyucocorticoids (2) |
|
Definition
|
|
Term
| what are the intermediate acting glucocorticoids (3) |
|
Definition
prednisone
methylprednisolone
triamcinolone |
|
|
Term
| what are the long acting glucocorticoids (2) |
|
Definition
betamethazone
dexamethazone |
|
|
Term
| what are the corticosteroid inhibitors (3) |
|
Definition
aminoglytethimide
ketoconazole
spironolactone |
|
|
Term
| what are the mineral corticoids |
|
Definition
|
|
Term
|
Definition
| high concentrations affect hypothalamus, stimulate corticoid and androgen receptors testing HPA axis |
|
|
Term
|
Definition
| tests HPA axis ysing synthetic ACTH residues 1-24 |
|
|
Term
|
Definition
antigenic: comes from animals
vasopressin par causes hyponatremia |
|
|
Term
| short acting glucocorticoid MOA |
|
Definition
| metabolized via reduction in liver to 11-8-hydeoxyderivative to be active |
|
|
Term
| side effects of short acting glucocirticoids (4) |
|
Definition
antiinflammatory
salt retension
minteral corticoid effects
less potent |
|
|
Term
| side effects of intermediate acting glucocorticoids (3) |
|
Definition
more potent
low salt retension
low mineralcorticoid effect |
|
|
Term
| side effects of long acting glucocorticoids (3) |
|
Definition
most potent
no salt retension
no mineralcorticoid effect |
|
|
Term
| shared side effects of all glucocirticoids (12) |
|
Definition
withdrawl: flare of of disease
acute adrenal insufficiency
HPA supression
fluid and electrolyte imbalance
hypertension
hyperglycemia
fat redistribution
osteoperosis
myopathy
behavorial changes
cataracts
increased infection |
|
|
Term
| why do glucocirticoids cause acute adrenal insufficiency |
|
Definition
| due to rapid withdrawl after prolonged use |
|
|
Term
| who do glucocirticoids cause HPA supression |
|
Definition
| occurs with supraphysiologocal doses for 2wk + |
|
|
Term
| how do glucocirticoids cause osteoperosis |
|
Definition
| inhibit ostroblasts and decrease bone formation |
|
|
Term
| how are glucocirticoids administered (9) |
|
Definition
| oral, injected, inhaled, topical, optic, opthalamic, enema, rectal, retro rocket |
|
|
Term
| where are glucocirticoids metabolized and eliminated |
|
Definition
metabolized in liver
excreted in kidney |
|
|
Term
| what affects the distribution of glucocirticoids |
|
Definition
| 90% bound to proteins (corticosteroid binding globulin, transcortin, albumin) |
|
|
Term
| what are the clinical uses of glucocirticoids (15) |
|
Definition
adrenal insufficiency
chronic primary adrenal insufficiency
congenital adrenal hypoplasia
RA
SLE
degrnerative joint
regional pain syndrome (injection)
allergies
asthma
PJP
influenza virus
ocular disease: supresses inflammation but increases IOP
cerebral edema
stroke
spinal cord injuty |
|
|
Term
| what are 2 diseases that cause chronic primary adrenal insufficiency |
|
Definition
adrenal surgery
cortex lesion (addisons) |
|
|
Term
|
Definition
|
|
Term
| aminoglytethimide clinical use |
|
Definition
|
|
Term
|
Definition
|
|
Term
| ketoconazole clinical use |
|
Definition
|
|
Term
|
Definition
| competes for mineralcorticoid receptor and stops Na reabsorption |
|
|
Term
| spironolactone clinical use |
|
Definition
|
|
Term
|
Definition
| act on DCT to increase reabsorption of Na into plasma and excretion of K and H |
|
|
Term
| fludorcortisone clinical use (4) |
|
Definition
addisons
severe salt loss
adrenogenital syndrome
orthostatic hypotension |
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