Adrenocorticoids

Question 1

metabolic effects of glucocorticoids

Answer 1

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

Question 2

catabolic effects of glucocorticoids

Answer 2

• 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

Question 3

what causes the immunosuppressive function of glucocorticoids

Answer 3

it decreases the amount of circulating lymphocytes, eosinophils, monocytes, and basophils away from the periphery (not by destruction)

Question 4

how does glucocorticoids prevent inflammation

Answer 4

• 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

Question 5

if glucocorticoid is given chronically, what does it suppress

Answer 5

release of ACTH, GH, TSH, and LH

Question 6

name some of the glucocorticoids

Answer 6

Beclomethasone
Dexamethasone
Hydrocortisone
Prednisone
Prednisolone
Triamcinolone

Question 7

what are the mineralcorticoids

Answer 7

Aldosterone

Fludrocortisone

Question 8

mechanism of mineralcorticoids

Answer 8

aldosterone and fludrocortisone promote reabsorption of sodium form distal DCT (Na/K ATPase) and collecting duct (ENAC) –> increased urinary excretion of H+ and K+

Question 9

what occurs with excessive levels of aldosterone or overdosage with synthetic mineralcorticoids

Answer 9

hypokalemia
metabolic alkalosis
increased plasma volume
hypertension

Question 10

what is Addison’s disease and what are symptoms seen

Answer 10

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)

Question 11

what drug is given to those with adrenal insufficiency

Answer 11

hydrocortisone and salt retaining fludrocortisone

Question 12

what occurs if decrease or lack of 21 beta hydroxylase

Answer 12

(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

Question 13

symptoms seen in Cushing’s syndrome

Answer 13

• moon facies
• truncal obesity
• thinning of hair
• muscle wasting
• purple straie
• diabetes
• osteoporosis
• poor wound healing
• hyperglycemia

same results if chronic use of glucocorticoids

Question 14

what is hyperaldosterism treated with

Answer 14

aldosterone antagonist - spironolactone

Question 15

why is dexamethasone used to suppress ACTH production

Answer 15

to figure out if excess glucocorticoids is due to excess ACTH or from somewhere else

Question 16

what causes maturation of fetal lung and its significance

Answer 16

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

Question 17

serious complications of long term use of glucocorticoids

Answer 17

• peptic ulcers
• hypomania or acute psychosis
• depression
• increased intraocular pressure –> glaucoma
• benign intracranial pressure

Question 18

types of patient that caution should be taken before giving glucocorticoids

Answer 18

• peptic ulcers
• heart disease
• hypertension
• varicella and tuberculosis
• psychoses
• diabetes
• glaucoma
• osteoporosis

Question 19

adverse of aldosterone antagonist (name it)

Answer 19

spironolactone

hyperkalemia
cardiac arrhythmias
menstrual abnormalities
gynecomastia (has anti androgenic properties)
sedation
headache

Question 20

name the synthesis inhibitors (inhibitor anywhere on the steroid producing pathway)

Answer 20

KAM

Ketoconazole
Aminoglutethimide
Metyrapone

Question 21

mechanism of aminoglutethimide

Answer 21

blocks the conversion of cholesterol to pregnelone hence no formation of all the steroid hormones

Question 22

mechanism of ketoconazole

Answer 22

antifungal that is an inhibitor of adrenal (reduced cortisol) and gonadal steroid synthesis (reduced testosterone)

Question 23

what has ketoconazole been used to treat

Answer 23

Cushing’s disease

Prostate cancer

Question 24

adverse effects of ketoconazole

Answer 24

inhibitor of CYP450

Question 25

mechanism of metyrapone

Answer 25

inhibitor of 11 hydroxylase hence inhibits formation of aldosterone and cortisol

Question 26

importance of metyrapone

Answer 26

only adrenal inhibiting drug that can be administered to pregnant women with Cushing’s syndrome

Question 27

adverse effect of metyrapone

Answer 27

salt and water retention

hirsutism (everything shunted to androgen synthesis)

Question 28

mechanism of mifepristone

Answer 28

glucocorticoid receptor antagonist

Question 29

when is mifepristone used

Answer 29

inoperable patients with ectopic ACTH secretion or adrenal carcinoma who have failed to respond to other therapeutic manipulations