Corticosteroids

Question 1

Glucocorticoid effects on inflammation

Answer 1

Increased lipocortin inhibits phospholipase A
Reduced NF-Kappa B levels
1. decreased proteolytic enzymes
2. decreased chemotactic & vasoactive cytokines
3. Decreased activity COX-2
4. Decreased activity NOS

Question 2

Cushing’s Syndrome

Answer 2

Excess cortisol
Causes: glucocorticoid therapy, adrenal tumors, pituitary hypersecretion, hypothalamic hypersecretion
Treatment: cortisol synthesis inhibitors (watch adrenal insufficiency)

Question 3

Dexamethasone Test

Answer 3

If HPA axis is intact cortisol levels will be decreased by high dose dexamethasone
Used because no interference with test

Overnight vs. Low dose vs. High Dose

Question 4

Aminoglutethimide

Answer 4

Mx: Inhibits CYP11A1 and less so CYP11B1
Use: controlling hypercortisolism caused by adrenal tumors and ACTH dependent causes
Oral Admin.
Adverse: long term can induce adrenal insufficiency, hypothyroidism, hirsutism,
May need to supplement with corticosteroids and fludrocortisones to replace mineralocorticoids
Drug interax: CYP inducer leading to increased metabolism of other drugs like Warfarin, Theophylline, Digitoxin

Question 5

Ketoconazole

Answer 5

Mx: High doses inhibit CYP17, very high doses inhibit CYP11A1, Inhibits corticotroph adenylate cyclase reducing ACTH
Use: Cushing’s Syndrome
Adverse: adrenal insufficiency
Drug interax: Strong inhibitor CYP1A2, 2C9, 3A4; inhibits P-glycoprotein;
Contraindicated for coadmin. w/ ergot derivitives, cisapride, or triazolam (risk of fatal heart arrythmias)

Question 6

Metyrapone

Answer 6

Mx: Selective inhibitor CYP11B1 reducing cortisol
Use: Hypercortisolism caused by adrenal tumors or ectopic ACTH production; Diagnostic test for Cushing’s
Adverse: Hirsutism,

Question 7

Mifepristone

Answer 7

Mx: Blocks release of glucocorticoid receptors from chaperones
Also progesterone antagonist (can induce abortion)
Use: inoperable ACTH tumors, adrenal tumors unresponsive to other therapy
Adverse: Vaginal bleeding

Question 8

Cosyntropin

Answer 8

synthetic ACTH

Administer to see if primary adrenal insufficiency

Question 9

Treatment of adrenal insufficiency

Answer 9

Primary - hydrocortisone and cortisone, supplement w/ fludrocortisone for mineralocorticoid effect
Secondary - no need for mineralocorticoid
Acute insufficiency?

Question 10

What is measured to diagnose CAH?

Answer 10

17-hydroxyprogesterone

Question 11

Treatment of aldosteronism

Answer 11

Surgery if unilateral adenoma
Aldosterone antagonist - Spironolactone (also progesterone agonist and androgen antagonist); Eplerenone - less side effects but expensive

Question 12

Once in remission, what happens to the therapy regimen? Why?

Answer 12

switch to every other day and give in morning to match circadian rhythm
This reduces HPA suppression

Question 13

Dexamethasone in pregnancy

Answer 13

category C pregnancy drug - birth defects