Adrenal Corticosteroid Pharmacology

Front 1

What's the definiton of a "corticosteroid"?

Back 1

mineralcorticoid or glucocorticoid

Front 2

What's the role of cortisol and cortisol analogs in the body?

Back 2

1. stimulate gluconeogenesis
2. mobilize amino acids from extrahepatic tissues as substrates for gluconeogenesis
3. inhibit glucose uptake in muscle (insulin resistance) to conserve glucose
4. break down fat in adipose tissues for muscles to use fatty acids as energy and the liver to use glycerol for gluconeogenesis

Front 3

How do glucocorticoids act on cells?

Back 3

Transactivation: Bind ligand in the cytoplasm, both enter the nucleus and bind glucocorticoid-response elements (GREs) to stimulate gene transcription.

Transrepression: Bind transcription factors such as NF-kB or AP-1 in the cytoplasm to shut down gene transcription, eg for pro-inflammatory genes such as IL-2

Front 4

What are glucocorticoids used for pharmacologically?

Back 4

endocrine: to determine the diagnosis and cause of Cushing's (dexamethasone) and to treat adrenal insufficiency and congenital adrenal hyperplasia.
Also for inflammatory, allergic and immunological disorders

Front 5

What are the side effects associated with glucocorticoids?

Back 5

-Cushing's
-hypothalamic-pituitary axis suppression
-topicals: skin atrophy, ecchymoses, purple striae, dermatoses, cataracts

Front 6

What factors influence how much of a topical glucocorticoid is absorbed?

Back 6

type of skin (intertiginous vs. forhead, scalp, face), occlusive dressing, inflammation and desquamation, being an infant

Front 7

How do glucocorticoids suppress the hyhpothalamic-pituitary axis?

Back 7

They block ACTH and so the adrenal gland atrophies. This isn't a problem until the patient is taken off steroids, at which point they crash. Thus the importance of tapering, or alternate-day therapy.

Front 8

How can a patient minimize the side effects of glucocorticoids?

Back 8

exercise decreases myopathy and osteoporosis.
exercise, calcium, vit D, bisphosphonates and ERT can decrease vertebral bone mineral loss (no such effect on femoral neck or distal radius).

Front 9

How do you treat adrenal insufficiency?

Back 9

glucocorticoids (prednisone or hydrocortisone).
During stress, tell them to double or triple their dose.
Add mineralcorticoids (Fludrocortisone) if it's primary adrenal insufficiency.

Front 10

What do mineralcorticoids do in the body?

Back 10

increase sodium reabsorption in the DCT
increase urinary excretion of potassium and hydrogen ions
increase BP (due to electrolyte changes)

Front 11

What mineralcorticoid is used pharmacologically, and what are its indications?

Back 11

Fludrocortisone.
Indications:
replacement therapy for primary adrenal insufficiency
tx for salt-losing adrenogenital syndrome
tx for orthostatic hypotension
tx for hypoaldosteronism

Front 12

What are the significant side effects of mineralcorticoids?

Back 12

edema, hypertension, hypokalemia

Front 13

How is DHEA used pharmacologically?

Back 13

Can replace androgen loss in women with adrenal insufficiency (less so in men, since adrenal production of DHEA is a much smaller contributor in male sex hormones than female sex hormones)
OTC, so no quality control, poor quality, can be dangerous.

Front 14

What drugs can be used to decrease glucocorticoids in Cushing's syndrome or adrenal carcinoma?

Back 14

*Ketoconazole (inhibits first step in cortisol synth and last step, also at therapeutic doses inhibits ACTH secretion by impairing corticotroph adneylate cyclase activation).
Mitotane (blocks 11-beta hydroxylase in adrenocortical mitochondria and first cortisol-synth step)
Aminoglutethimide (blocks first step in cortisol biosynthesis)
Metyrapone (blocks 11-beta hydroxylase)

Front 15

What drugs will block mineralcorticoid receptors?

Back 15

spirinolactone and eplerenone block aldosterone receptors.

Front 16

What are drospirenone and triamterene?

Back 16

drospirenone: antagonizes aldosterone effects.

triamterene: reduces Na+ reabsorption and blood pressure