Adrenal Pharmacology Flashcards Preview

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Flashcards in Adrenal Pharmacology Deck (40):
1

Causes of hyperaldosteronism

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

2

Liddle's Syndrome

mutation in epithelial sodium channel leading to hyperaldosteronism

3

Tx for hyperaldosteronism

correct underlying cause, adrenalectomy, medications

4

Amiloride/midamore

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

5

Spironolactone/adlactone

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

6

Eplerenone/Inspra

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

7

T/F spirinolactone can also bind androgen and progesterone receptors

T

8

Indications for spirinolactone

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

9

Adverse effects of spirinolactone

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

10

Contraindications for spirinolactone

renal impairement, hyperkalemia, pregnancy

11

T/F Eplerenone can also bind androgen and progesterone receptors

F --> more specific than spirinolactone

12

Indications for Eplerenone

potassium sparing diuretic, primary hyperaldosteronism

13

Contraindications for Eplerenone

renal impairement, hyperkalemia, pregnancy

14

Contraindications for Amiloride

renal impairement, hyperkalemia

15

What do we monitor when tx hyperaldosteronism?

dehydration, bp, serum electrolytes, gynecomastia

16

Causes of mineralocorticoid deficiency

primary adrenal insufficiency, hyporeninemia (diabetic nephropathy),

17

Serum state of mineralocorticoid deficiency

high K, low Na, low volume

18

Tx of mineralocorticoid

replacement and fludrocortisone (Florinef)

19

Fludrocortisone

syntehtic mineralocorticoid --> maintain volume and control hyperkalemia

20

Side effects of Fludrocortisone

hypokalemia, volume overload

21

Hypercortisolemia causes

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

22

Tx of Hypercortisolemia

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

23

Mifepristone tx of Hypercortisolemia

antagonist for glucocorticoid receptors --> hard to monitor effects

24

Mitotane tx of Hypercortisolemia

adrenal cytotoxic

25

Drugs that inhibit steroidogenesis for hypercortisolemia

metyrapone, ketoconazole, aminoglutethimide, etomidate

26

Drugs that inhibit ACTH secretion for hypercortisolemia

pasireotide (somatostatin analog), cabergolien

27

T/F pituitary adenomas express somatostatin and dopamine receptors

T --> can use pasireotide and cabergolinea s Tx

28

Pasireotide MOA

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

29

Pasireotide side effects

hyperglycemia, cardiac conduction, gallstones

30

Enzyme blocked by metyrapone, ketoconazole, mitotane

11beta hydroxylase --> 11 deoxycortisol to cortisol

31

Enzymes blocked by ketoconazole

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

32

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

F --> work on pituitary so only ACTH dependent

33

T/F ketoconazole can increase liver function tests

T --> must monitor LFT

34

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

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

35

Tx of glucocorticoid deficiency

hydrocortisone, prednisone, dexamethasone

36

Sick day replacement

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

37

Stress dose replacement

for inpatient illness/perioperative: IV or PO

38

Acute dose replacement for shock/adrenal crisis

IV --> taper down when appropriate

39

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

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

40

Metyrapone test for secondary adrenal insufficiency

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