62: Adrenal Agents Flashcards
mineralocorticoid =
aldosterone
glucocorticoid =
hydrocortisone
medulla releases. ..
epi
NE
action of aldosterone/mineralcorticoid
- increases sodium reabsorption at renal collecting tubule
- increases excretion of K+
- plays important role in regulating blood pressure
action of cortisol/glucocorticoid
- restores homeostasis after exposure to stress
- released in circadian rhythm and with stress
- increases blood glucose
- antiinflammatory
action of androgens (DHEA and androstenedione)
- can be converted to testosterone
- major source of female adrogens
HPA axis starts in hypothalamus with CRH –>
ant. pit —> ACTH —> Adrenal cortex –> cortisol and adrenal androgens
aldosterone production is regulated by…
angiotensin II
blood K+
glucocorticoid and mineralocorticoid receptors are…
nuclear hormone receptors –> change gene expression
converts active cortisol into inactive cortisone
11B - HSD2
cortisone is converted into cortisol by..
11B-HSD1
hydroxylation of cortisone and prednisone by _____ in necessary to activate into active form
11B-HSD1
primary adrenal insufficiency =
addison’s disease
deficiency in cortisol, aldosterone, and androgens
observe elevated ACTH and CRH due to loss of negative feedback
treatment for addison’s disease
oral cortisol
fludrocortiosne
increase or decrease supplementary cortisol in times of stress?
increase - to prevent hypotension and shock
dosing regimen is usually 2/3 morning 1/3 afternoon
describe pituitary disease
- decrease in ACTH causes increase in CRH
- decrease in cortisol
describe hypothalamic disease
- decrease in CRH causes decrease in ACTH
- decrease in cortisol
treatment secondary adrenal insufficiency
just cortisol, no fludrocortisone
chronic cortisol excess –>
cushing’s syndrome
causes of elevated cortisol (4)
- chronic glucocorticoid therapy
- pit tumor that causes hypersecretion of ACTH
- ectopic hypersecretion of ACTH by non-pit tumors
- adrenal tumor that hypersecretes cortisol
Increased Cortisol AND
– decreased CRH with increased ACTH
– decreased CRH and ACTH
– pituitary hypersecretion of ACTH or ectopic ACTH production
– adreanl adenoma
dexamethasone suppression test – 50% reduction in cortisol
must be pit. hypersecretion of ACTH
adrenal adenoma and ectopic ACTH would show no reduction in cortisol
MOA ketoconazole
inhibits 17alpha
used to treat cushings
can induce liver toxicity
MOA metyrapone
inhibits 11B
diagnositc agen used to evaluate ACTH production
off-label cushings treatment
MOA mifepristone
high dose - glucocorticoid receptor antagonist
used to treat pt. with ectopic ACTH or adrenal carcinoma
mechanisms of anti-inflammatory effects of corticosteroids (6)
- inhibition of phospholipase A2 activity
- inhibition ofcyclooxygenase induction
- inhibition of NO synthase induction
- inhibition of cytokine production
- inhibition of mast cell activity and reduction of mast cell number
- vasoconstriction
first line tx with patients with persistent asthma
inhaled corticosteroids
MOA fluticasone in asthma
- reduces leaky vascual endothelial cells
- decreases adhesion molecules in airway
- increases epithelial integrity
- decreases growth of airway smooth muscle cells
reciprocal interactions b/w inhaled corticosteroids and B2 receptor agonists
corticosteroids: - increase B2 receptor expression to prevent desensitization of B2 receptors
B2 agonists:
- increase nuclear translocation of GRs to increase binding of GR to GREs on genes
individuals with liver disease or chronic inflammatory disease can decrease serum prtns, therefore…
decrease the dosage of glucocorticoids because without binding to prtns, more will be free and active
doses less than ___– have not been associated with impaired growth
400 ug/d
concurrent use of glucorticoid and cyclosporin?
increase levels of each other by inhibiting metabolism
why is it necessary to taper a pt off long term glucocorticoid therapy slowly?
to reduce HPA axis suppression and allow body to make its own cortisol to respond to stress
what is the mechanism by which high doses cortisol can lead to HTN or hypokalemia? would this same mechanism be observed with dexamthasone?
Mineralocorticoid receptor effects
no- it doesn’t hit those receptors
