Adrenal Pharmacology Flashcards Preview

Repro-Endo > Adrenal Pharmacology > Flashcards

Flashcards in Adrenal Pharmacology Deck (28):
1

What are 4-5 causes of hyperaldosteronism?

Primary
Secondary (heart failure and cirrhosis)
Liddle's syndrome
Deoxycorticosterone-mediated
Licorice ingestion

2

3 stimulators of aldosterone?

Angiotensin II
High K+
ACTH

3

What's the mutation in Liddel's syndrome?

Sodium transporter (ENaC) is overactive.
Excess Na+ is reabsorbed, along with water, and K+ is excreted.

4

2 MoAs of drugs that treat hyperaldosteronism? Drugs that do each?

Inhibition of ENaC - amiloride.
Antagonism of mineralocorticoids - spironolactone, eplerenone.

5

3 activities of spironolactone?

Mineralcorticoid antagonist.
Androgen and progesterone receptor antagonist.

6

Side effects of spironolactone? (4 categories)

Can mimic hypoaldosteronism: hyperkalemia, hypovolemia.
Androgen antagonism: gynecomastia, impaired libido, impotence in men.
Progesterone antagonism: irregular uterine bleeding in women.
Teratogenic.

7

How is eplerenone different from spironolactone? Why isn't it used more?

It specifically antagonizes the mineralocorticoid receptor - doesn't antagonize progesterone and androgens.
It's really expensive.

8

Take-home point about amiloride?

It has a weak diuretic and anti-hypertensive effect compared to spironolactone.

9

3 things to monitor when using K+ sparing diuretics and mineralocorticoid antagonists?

Dehydration
BP
Serum lectrolytes and creatinine.

10

2 causes of mineral corticoid deficiency?

Primary adrenal insufficiency
Hyporeninemia (too little renin)

11

One example of a cause of hyporeninemia?

Diabetic nephropathy.

12

Treatment for mineralocorticoid deficiency? Side effects?

Fludrocortisone (Florinef) - synthetic mineralocorticoid.
Side effects = hyperaldosteronism (hypokalemia, hypervolemia).

13

When giving patients fludrocortisone, what are 3 symptoms you want to ask the patient about?

Presyncope, lightheadedness.
Swelling/edema in hands and feet.
Salt cravings.

14

When giving patients fludrocortisone, what do you have to monitor?

Orthostatic BP/HR (dehydration).
Serum Na+, K+, plasma renin.

15

2 less common medical (non-surgical) treatments for Cushing's syndrome? MoA?

Mitotane - adrenal cytotoxic.
Mifepristone - glucocorticoid receptor antagonist (recall: also progesterone antagonist).

16

2 MoAs of drugs more commonly used for hypercortisolism? Drugs that do each?

Inhibit steroidogenesis enzymes -metyrapone, ketoconazole.
Inhibit ACTH secretion -pasireotide (somatostain analogue).

17

Advantage of somatostatin analogues ("-reotides") over steroidogenesis inhibitors for treatment of hypercortisolism?

The steroidogenesis inhibitors are hepatotoxic.
(ketoconazole is an anti-fungal, which just tend to have nasty side effects).
But obviously inhibiting ACTH release isn't going to work on ACTH-independent adrenal adenomas.

18

When treating with cortisol-lowering drugs, monitor...

to make sure you're not overtreating or undertreating.

19

What's deficient in primary adrenal insufficiency?
How about secondary adrenal insufficiency?

Primary: loss of both glucocorticoids and mineralocorticoids.
Secondary: Deficiency of glucorticoids anyway.

20

How come you still get aldosterone secretion when ACTH goes away?

ACTH is only small contributor to aldosterone stimulation.
Angiotensin II and K+ are more important.

21

Why might hydrocortisone be preferred for treatment of glucocorticoid deficiency?

Shorter half-life, can mimic natural fluctuations in cortisol.

22

If people are getting glucocorticoid replacement therapy, what must they do when they get an infection?

Increase the dose.
(don't get confused about immune suppression, being sick increases need for cortisol and can cause Addisonian crisis)

23

Why do high cortisol levels mimic hyperaldosteronism?

High levels overwhelm the shunt to corticosterone.

24

How do you test for primary adrenal insufficiency?

See if cortisol low in the morning.
If low, give synthetic ACTH, and see if cortisol rises in response.
(low cortisol that fails to rise would be primary adrenal insufficiency)

25

How do you test for secondary adrenal insuffiency? What's the normal result?

(In inpatient setting...) Give metyrapone, which inhibits the last step in cortisol synthesis. Low synthesis should drive ACTH release.
If pituitary working normally, 11-deoxycortisol (last metabolite before cortisol) will build up.

26

What are the most of the synthetic glucocorticoid designed to have?

More anti-inflammatory activity, less mineralocorticoid activity.
Eg. prednisone, dexamethasone.

27

Which synthetic glucocorticoid is best for immediate hypersensitivity reaction?

Prednisone.

28

What's cosyntropin?

ACTH analogue - used to test for secondary adrenal insufficiency.