Adrenocoticosteroids and Adrenocortical Antagonists Flashcards
Use of adrenocortical steroids?
diagnosis and treatment of disorders of adrenal function, treatment of variety of inflammatory and immunologic disorders
Control secretion of adrenocortical steroids?
pituitary release of corticotropin ACTH
Control secretion of aldosterone?
angiotensin
Physiologic effects of cortisol?
regulation of intermediary metabolism, cardiocascular function, growth, immunity
Pattern of cortisol secretion?
circadian, pulses peak early morning hours and after meals
Cortisol is bound to what in plasma?
corticosteroid binding globulin
small amount is free or bound to albumin
When is CBG increased?
pregnancy, esterogen admin, hyperthyroidsim
When is CBG decreased?
hypothyroidism, genetic defects in synthesis, and protein def
Synthetic corticosteroids largely bind to?
albumin
When is half life of cortisol increased?
hydrocortisone admin in large amt, stress, hypothyroidism, liver disease
Glucocorticoids mediate their effect through?
glucocorticoid receptors (nuclear receptors)
in abscence of hormone, what do glucocorticoid receptors do?
cytoplasmic, in oligomeric complexes with heat shock proteins
Most important heat shock protein for glucocorticoid receptors?
HSP90
GRE?
glucocorticoid receptor elements
what the receptor-ligand complex binds to (after hormone binds to glucocorticoid receptor the receptor and the hormone then move into the nucleus and bind to this)
When the receptor is bound to heat shock protein is it activated/ inactived?
inactivated
How does glucocorticoids stimulate gluconeogeneisis or glycogen synthesis in the fasting state?
stimulate phosphoenolpyruvate carboxylase, glucose-6 phosphate, glycogen synthase
How does glucocorticoids inhibit inflammation?
inflammation is extraversion and inflitration of leukocytes into the affected tissue, glucocorticoids inhibit the white cell adhesions with endothelial cells
glucocorticoids effect on macrophages?
limit ability to phagocytose and kill micoorganisms and to produce tumor necrosis factor alpha, interleukin 1, metalloproteinases, plasminogen activator
How else do glucocorticoids affect inflammation?
reduce prostaglandins, leukotriene, platelet activating factor synthesis that results from phospholipase A2
reduce expression of cyclooxygenase 2
Short toe medium acting glucocorticoids?
Hydrocortisone Cortisone Prednisone Prednisolone Methylprednisolone Meprednisone
Intermediate acting glucocorticoids?
Triamcinolone
Paramethasone
Fluprednisolone
Long acting glucocorticoids?
Betamethasone
Dexamethasone
Mineralcorticoids?
Fludrocortisone
Desoxycorticocosterone acetate
Treatment for Chronic Adrenocortical insufficiency (Addison’s disease)?
Hydrocortisone given daily, increased amounts during stress
supplemented with fludrocortisone (salt retaining)
long acting not administered
Treatment for acute Adrenocortical insufficiecny?
large amount of parenteral hydrocortisone in addition to correction of fluid and electrolyte abnormalities (sodium succinate or phosphate)
Treatment for Congenital Adrenal hyperplasia?
may be in acute adrenal crisis, treat as such
(large amount of parenteral hydrocortisone in addition to correction of fluid and electrolyte abnormalities (sodium succinate or phosphate))
once stable, oral hydrocortisone is given
alternate day therapy with prednisone (greater ACTH supression with out growth inhibition)
Fludrocorsine should be administered by mouth
Treatment for Cushing’s syndrome?
surgical removal of the tumor producing ACTH or cortisol, irradiation of pituitary tumor, resection of one or both adrenals
large dose of cortisol during and after surgery
Primary aldosteronism?
excessive production of aldosterone by an adrenal adenoma
Treatment for primary aldosteronism?
Not with fludrocortisone (patients fail to retain sodium and secretion not reduced)
With spironolactone
Glucocorticoids use for diagnosis?
dexamethasone is used because use of small quantities reduces the possibility of confusion in interpretation
dexamthasone suppression test
diagnosis of Cushing’s syndrome
give dexamethasone in evening and measure in morning, Cushing patient with have a high level
(over 5 mcg/dl)
distinguish hypercortisolism due to anxiety, depression, and alcoholsim and Cushing’s?
combined test consisting of dexamethasone followed by standard corticotropin release hormone test
Distinguish a patient with Cushing from steroid producing tumors?
large dose of dexamethasone
should produce a 50 % reduction in hormone
ACTH low in cortisol producing adrenal tumor and elevated in ectopic ACTH producing tumor
What type of synthetic glucocorticoids are better?
medium to intermediate acting, keep dose low
Should therapy be stopped abruptly/ decreased?
no
cxr and tuberculin test for TB
ck for diabestes, peptic ulcer, osteoporosis, and pysch disturbance
Cushing’s syndrome?
need for insulin, weight gain, myopathy, thinning of skin, osteoporosis, diabetes, aseptic necrosis of hip
Long term effects of glucocorticoids?
hypokalemic, hypochlorinc alkalosis, rise in BP
If dosage is reduced too rapidly?
anorexia, nausea, vomit, weight loss, lethargy, headache, fever, joint or muscle pain, postural hypotension
Alternative day administration?
works because you allow recovery period between each dose, allowing large doses to be given
treat severe autoimmune?
prednisone
Ideal treatment?
medium or intermediate acting synthetic , single morning dose
Treatment for asthma?
Beclomethasone dipropionate
budesonide,flunisolide and mometasone furoate
Treatment for allergic rhinitis?
Beclomethansone dipropionate, triamcinolone acetonide, budesonide, flunisolide, and momestasone furoate
excessive aldosterone can lead to?
hypokalemia, metabolic alkalosis, increased plasma volume, and hypertension
Account for specificty of mineralcorticoids in kidney?
enzyme 11 beta hydroxysteroid dehydrogenase type 2
Regulate DOC?
deoxycorticosterone is controlled by ACTH
increased DOC release?
adrenocortical carcinoma and congenital adrenal hyperplasia
Most widely used mineralcorticoid?
Fludrocortisone
Adrenal synthetic steroid?
P450c11 (11-hydroxylase)
P450c17 (17-hydroxylase)
P450c21 (21-hydroxylase)
Treatment for carcinoma of the breast?
Aminogltethimide
bloack conversion of cholesterol to pregnenolone
Aminogltethimide can also be used?
reduce steroid secretion in patients with Cushing’s Syndrome
Ketoconazole?
an antifungal, inhibitory effects on steroid biosynthesis are seen at high doses
used for Cushing’s syndrome
Only adrenal inhibiting med administered to pregnant patient’s with Cushing’s syndrome?
Metyrapone
Metyrapone and Cushing Syndrome?
can reduce cortisol in endogenous Cushing Syndrome
adverse effects of Metyrapone?
salt and water rentention and hirsuitism
another use for Metyrapone?
test adrenal function
Mifeprisone 2 ways has antiglucocorticoid activity?
1 blocking glucocorticoid receptor, stablizie Hsp-glucocorticoid receptor complex and inhibit pf hte dissociation of RU-286 bound glucocorticoid receptor from the Hsp chaperone proteins
2 alter the interaction of glucocorticoid receptor with coregulators, favoring the formation of a transcriptionally inactive complex in the cell nucleus
Spironolactone MOA and clin use?
7alpha acetylthiosprionolactone
used for primary aldosteronism, useful to establish signs and symptoms and when surgery is delayed, prep for surgery
adrogen antagonist, treat hirtuism in women
diruetic
treat hirtuism?
Spironolactone
Eplerenone MOA and clin use?
Aldosterone antagonist, treat hypertension
more selective than Spironolactone
Drospirenone MOA and clin use?
oral contraceptive
antagonizes the effects of aldosterone
