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Pharm Adrenal Cortex
KYCOM Block 11
57
Pharmacology
Graduate
10/19/2013

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Cards

Term
what does HPA stand for
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
what is steroidogenesis
Definition
ACTH increases due to impaired cortisol synthesis
Term
what happens if the inner cortex does not get stimulation
Definition
artophy
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
P450
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
ACTH and cosyntropin
Term
what are the short acting glyucocorticoids (2)
Definition
hydrocortisone
cortisone
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
fludrocortisone
Term
MOA ACTH
Definition
high concentrations affect hypothalamus, stimulate corticoid and androgen receptors testing HPA axis
Term
MOA cosyntropin
Definition
tests HPA axis ysing synthetic ACTH residues 1-24
Term
side effects ACTH (2)
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
MOA aminoglytethimide
Definition
inhibit P450 SCC
Term
aminoglytethimide clinical use
Definition
cushings
Term
ketoconazole MOA
Definition
inhibits C17-20 lyase
Term
ketoconazole clinical use
Definition
cushings
Term
spironolactone MOA
Definition
competes for mineralcorticoid receptor and stops Na reabsorption
Term
spironolactone clinical use
Definition
hyperaldosteronism
Term
fludorcortisone MOA
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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