Adrenal Pharmacology

Question 1

What are 4-5 causes of hyperaldosteronism?

Answer 1

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

Question 2

3 stimulators of aldosterone?

Answer 2

Angiotensin II
High K+
ACTH

Question 3

What’s the mutation in Liddel’s syndrome?

Answer 3

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

Question 4

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

Answer 4

Inhibition of ENaC - amiloride.

Antagonism of mineralocorticoids - spironolactone, eplerenone.

Question 5

3 activities of spironolactone?

Answer 5

Mineralcorticoid antagonist.

Androgen and progesterone receptor antagonist.

Question 6

Side effects of spironolactone? (4 categories)

Answer 6

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

Question 7

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

Answer 7

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

Question 8

Take-home point about amiloride?

Answer 8

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

Question 9

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

Answer 9

Dehydration
BP
Serum lectrolytes and creatinine.

Question 10

2 causes of mineral corticoid deficiency?

Answer 10

Primary adrenal insufficiency

Hyporeninemia (too little renin)

Question 11

One example of a cause of hyporeninemia?

Answer 11

Diabetic nephropathy.

Question 12

Treatment for mineralocorticoid deficiency? Side effects?

Answer 12

Fludrocortisone (Florinef) - synthetic mineralocorticoid.

Side effects = hyperaldosteronism (hypokalemia, hypervolemia).

Question 13

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

Answer 13

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

Question 14

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

Answer 14

Orthostatic BP/HR (dehydration).

Serum Na+, K+, plasma renin.

Question 15

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

Answer 15

Mitotane - adrenal cytotoxic.

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

Question 16

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

Answer 16

Inhibit steroidogenesis enzymes -metyrapone, ketoconazole.

Inhibit ACTH secretion -pasireotide (somatostain analogue).

Question 17

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

Answer 17

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.

Question 18

When treating with cortisol-lowering drugs, monitor…

Answer 18

to make sure you’re not overtreating or undertreating.

Question 19

What’s deficient in primary adrenal insufficiency?

How about secondary adrenal insufficiency?

Answer 19

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

Question 20

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

Answer 20

ACTH is only small contributor to aldosterone stimulation.

Angiotensin II and K+ are more important.

Question 21

Why might hydrocortisone be preferred for treatment of glucocorticoid deficiency?

Answer 21

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

Question 22

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

Answer 22

Increase the dose.

don’t get confused about immune suppression, being sick increases need for cortisol and can cause Addisonian crisis

Question 23

Why do high cortisol levels mimic hyperaldosteronism?

Answer 23

High levels overwhelm the shunt to corticosterone.

Question 24

How do you test for primary adrenal insufficiency?

Answer 24

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)

Question 25

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

Answer 25

(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.

Question 26

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

Answer 26

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

Question 27

Which synthetic glucocorticoid is best for immediate hypersensitivity reaction?

Answer 27

Prednisone.

Question 28

What’s cosyntropin?

Answer 28

ACTH analogue - used to test for secondary adrenal insufficiency.