Adrenal Pharmacology

Question 1

Causes of hyperaldosteronism

Answer 1

Primary, Secondary (cirrhosis, heart failure), Liddle’s, deoxycorticosterone mediated, Licorice

Question 2

Liddle’s Syndrome

Answer 2

mutation in epithelial sodium channel leading to hyperaldosteronism

Question 3

Tx for hyperaldosteronism

Answer 3

correct underlying cause, adrenalectomy, medications

Question 4

Amiloride/midamore

Answer 4

K+ sparing diuretic that blocks ENaC and inhibits sodium reabsorptin into distal tubules

Question 5

Spironolactone/adlactone

Answer 5

decrease action of mineralocorticoids –> prevent binding of aldosterone to mineralocorticoid receptor –> reduced upregulation of ENaC, K+ channel, and sodium/potassium pump

Question 6

Eplerenone/Inspra

Answer 6

decrease action of mineralocorticoids –> prevent binding of aldosterone to mineralocorticoid receptor –> reduced upregulation of ENaC, K+ channel, and sodium/potassium pump

Question 7

T/F spirinolactone can also bind androgen and progesterone receptors

Answer 7

T

Question 8

Indications for spirinolactone

Answer 8

primary hyperaldosteronism, PCOS/hirsutism (b/c of non specific action), K+ sparing diuretic: essential hypertension, CHF, cirrhosis, hephrosis

Question 9

Adverse effects of spirinolactone

Answer 9

hyperkalemia, volume depletion, gynecomastia, impaired libido, impotence, menstrual irregularities, teratogenic

Question 10

Contraindications for spirinolactone

Answer 10

renal impairement, hyperkalemia, pregnancy

Question 11

T/F Eplerenone can also bind androgen and progesterone receptors

Answer 11

F –> more specific than spirinolactone

Question 12

Indications for Eplerenone

Answer 12

potassium sparing diuretic, primary hyperaldosteronism

Question 13

Contraindications for Eplerenone

Answer 13

renal impairement, hyperkalemia, pregnancy

Question 14

Contraindications for Amiloride

Answer 14

renal impairement, hyperkalemia

Question 15

What do we monitor when tx hyperaldosteronism?

Answer 15

dehydration, bp, serum electrolytes, gynecomastia

Question 16

Causes of mineralocorticoid deficiency

Answer 16

primary adrenal insufficiency, hyporeninemia (diabetic nephropathy),

Question 17

Serum state of mineralocorticoid deficiency

Answer 17

high K, low Na, low volume

Question 18

Tx of mineralocorticoid

Answer 18

replacement and fludrocortisone (Florinef)

Question 19

Fludrocortisone

Answer 19

syntehtic mineralocorticoid –> maintain volume and control hyperkalemia

Question 20

Side effects of Fludrocortisone

Answer 20

hypokalemia, volume overload

Question 21

Hypercortisolemia causes

Answer 21

ACTH dependent: pituitary adenoma, ectopic
ACTH independent: adrenocortical adenoma, bilateral adrenal hyperplasia
Iatrogenic or surreptitious

Question 22

Tx of Hypercortisolemia

Answer 22

correct underlying cause/surgery, medical tx is second line –> adrenal cytotoxic, decrease action of glucocorticoids, decrease glucorticoid production

Question 23

Mifepristone tx of Hypercortisolemia

Answer 23

antagonist for glucocorticoid receptors –> hard to monitor effects

Question 24

Mitotane tx of Hypercortisolemia

Answer 24

adrenal cytotoxic

Question 25

Drugs that inhibit steroidogenesis for hypercortisolemia

Answer 25

metyrapone, ketoconazole, aminoglutethimide, etomidate

Question 26

Drugs that inhibit ACTH secretion for hypercortisolemia

Answer 26

pasireotide (somatostatin analog), cabergolien

Question 27

T/F pituitary adenomas express somatostatin and dopamine receptors

Answer 27

T --> can use pasireotide and cabergolinea s Tx

Question 28

Pasireotide MOA

Answer 28

binds somatostatin receptor --> reduced cAMP --> decrease POMC --> decrease ACTH secretion + increased apoptosis/decreased cell growth via PTPase activation

Question 29

Pasireotide side effects

Answer 29

hyperglycemia, cardiac conduction, gallstones

Question 30

Enzyme blocked by metyrapone, ketoconazole, mitotane

Answer 30

11beta hydroxylase --> 11 deoxycortisol to cortisol

Question 31

Enzymes blocked by ketoconazole

Answer 31

1 alpha, 3beta, 11beta --> nonspecific in steroidogenesis pathway

Question 32

T/F somatostatin and dopamine analogs can be used to treat both acth dependent/independent hypercortisolemia

Answer 32

F --> work on pituitary so only ACTH dependent

Question 33

T/F ketoconazole can increase liver function tests

Answer 33

T --> must monitor LFT

Question 34

Why does secondary adrenal insufficiency only affect glucocorticoids but primary adrenal insufficiency affects both glucocorticoids and mineralocorticoids?

Answer 34

If adrenal is not working, cannot have cortisol or aldosterone; if pituitary ACTH is not available, cortisol will not be produced but angiotensin II and potassium can stimulate aldosterone production

Question 35

Tx of glucocorticoid deficiency

Answer 35

hydrocortisone, prednisone, dexamethasone

Question 36

Sick day replacement

Answer 36

outpt with fever/illness --> double or triple daily dose

Question 37

Stress dose replacement

Answer 37

for inpatient illness/perioperative: IV or PO

Question 38

Acute dose replacement for shock/adrenal crisis

Answer 38

IV --> taper down when appropriate

Question 39

T/F at doses greater than 60-80mg daily, hydrocortisone has mineralocorticoid activity

Answer 39

T --> can overwhelm 11beta hsd2 shunt in aldosterone sensitive tissues like kidney --> excess hydrocortisone can bind and activate MCR --> dont need to supplement MC until HC <60-80

Question 40

Metyrapone test for secondary adrenal insufficiency

Answer 40

to distinguish betwn primary/secondary insufficiency after cosyntropin --> metyrapone blocks cortisol production (11 beta hydroxylase)--> low cortisol should stimulate ACTH to restart cortisol production// if normal, ACTH will result in buildup of cortisol precursor: 11 deoxycortisol // if secondary insufficiency, ACTH will not start up --> no buildup of 11 deoxycortisol