Adrenocorticoids Flashcards
metabolic effects of glucocorticoids
in fasting state
- increase gluconeogenesis by liver
- release of AA from muscle catabolism
- inhibition of peripheral glucose uptake
- stimulation of lipolysis
all done for adequate glucose supply for brain
catabolic effects of glucocorticoids
- osteoporosis in Cushing’s syndrome
- growth retardation in children
- antagonize the effect of vit D on calcium reabsorption
- increase in free fatty acid
- fat distribution –> moon facies, buffalo hump, loss of fat in extremities
what causes the immunosuppressive function of glucocorticoids
it decreases the amount of circulating lymphocytes, eosinophils, monocytes, and basophils away from the periphery (not by destruction)
how does glucocorticoids prevent inflammation
- inhibits function of tissue macs and other APCs
- inhibition of phospholipase A2 inhibiting arachidonic acid
- reduce expression of COX-2
- inhibit MAPK phosphatase –> no MAPK activated proinflammatory pathway
if glucocorticoid is given chronically, what does it suppress
release of ACTH, GH, TSH, and LH
name some of the glucocorticoids
Beclomethasone Dexamethasone Hydrocortisone Prednisone Prednisolone Triamcinolone
what are the mineralcorticoids
Aldosterone
Fludrocortisone
mechanism of mineralcorticoids
aldosterone and fludrocortisone promote reabsorption of sodium form distal DCT (Na/K ATPase) and collecting duct (ENAC) –> increased urinary excretion of H+ and K+
what occurs with excessive levels of aldosterone or overdosage with synthetic mineralcorticoids
hypokalemia
metabolic alkalosis
increased plasma volume
hypertension
what is Addison’s disease and what are symptoms seen
adrenal insufficiency - no mineralcorticoids and glucocorticoids
- weakness and fatigue
- weight loss (lack of glucocorticoids)
- inability to maintain blood glucose when fasting (lack of glucocorticoids)
- hyperpigmentation (increase in ACTH release with MSH)
- hypotension (lack of mineralcorticoids)
what drug is given to those with adrenal insufficiency
hydrocortisone and salt retaining fludrocortisone
what occurs if decrease or lack of 21 beta hydroxylase
(21 year olds can only have sex – make androgens only)
they can’t make aldosterone or glucocorticoids –> all directed to formation of testosterone –> too much testosterone in women –> virilization
symptoms seen in Cushing’s syndrome
- moon facies
- truncal obesity
- thinning of hair
- muscle wasting
- purple straie
- diabetes
- osteoporosis
- poor wound healing
- hyperglycemia
same results if chronic use of glucocorticoids
what is hyperaldosterism treated with
aldosterone antagonist - spironolactone
why is dexamethasone used to suppress ACTH production
to figure out if excess glucocorticoids is due to excess ACTH or from somewhere else
what causes maturation of fetal lung and its significance
fetal lung matures by fetal production of cortisol in last few weeks before birth
-mother who is about to have a preterm baby is given dexamethasone to speed up lung maturation to prevent respiratory distress syndrome
serious complications of long term use of glucocorticoids
- peptic ulcers
- hypomania or acute psychosis
- depression
- increased intraocular pressure –> glaucoma
- benign intracranial pressure
types of patient that caution should be taken before giving glucocorticoids
- peptic ulcers
- heart disease
- hypertension
- varicella and tuberculosis
- psychoses
- diabetes
- glaucoma
- osteoporosis
adverse of aldosterone antagonist (name it)
spironolactone
hyperkalemia cardiac arrhythmias menstrual abnormalities gynecomastia (has anti androgenic properties) sedation headache
name the synthesis inhibitors (inhibitor anywhere on the steroid producing pathway)
KAM
Ketoconazole
Aminoglutethimide
Metyrapone
mechanism of aminoglutethimide
blocks the conversion of cholesterol to pregnelone hence no formation of all the steroid hormones
mechanism of ketoconazole
antifungal that is an inhibitor of adrenal (reduced cortisol) and gonadal steroid synthesis (reduced testosterone)
what has ketoconazole been used to treat
Cushing’s disease
Prostate cancer
adverse effects of ketoconazole
inhibitor of CYP450
mechanism of metyrapone
inhibitor of 11 hydroxylase hence inhibits formation of aldosterone and cortisol
importance of metyrapone
only adrenal inhibiting drug that can be administered to pregnant women with Cushing’s syndrome
adverse effect of metyrapone
salt and water retention
hirsutism (everything shunted to androgen synthesis)
mechanism of mifepristone
glucocorticoid receptor antagonist
when is mifepristone used
inoperable patients with ectopic ACTH secretion or adrenal carcinoma who have failed to respond to other therapeutic manipulations
