Synthetic ACTH - Only used to assess hypothalamo-pituitary-adrenal axis - No therapeutic use/advantage over corticosteroids

Pharm 4 Adrenal Flashcards by Philip Lichtenstein

5 layers of adrenal gland

Capsule
Zona glomerulosa
Zona fasiculata
Zona reticularis
Medulla

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Zona glomerulosa - product, stimulus

Mineralocorticoids

-Angiotensin II, K+

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Zona fasiculata - product, stimulus

Glucocorticoids, Androgens, Estrogens

-ACTH

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Zona reticularis - product, stimulus

Glucocorticoids, Androgens, Estrogens

-ACTH

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Medulla - product, stimulus

Epinephrine

-Sympathetic activation

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3 Glucocorticoid drugs & duration

Prednisone - short
Triamcinolone - intermediate
Dexamethasone - long

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Glucocorticoid drug that is salt retaining

Prednisone

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Glucocorticoid drug - strongest anti-inflammatory

Dexamethasone

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Glucocorticoid drug - topical

Triamcinolone and dexamethasone

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Prednisone activity

Inactive until hydroxylated to Prednisolone

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Endogenous cortisol secretion inhibitors

GABA, opioids, cortisol

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ACTH

Adrenocorticotrophic hormone

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ACTH secretion

CRH -> POMC (pro-opiomelanocortin)

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Adrenal steroid storage

None, secreted immediately

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-Cosyntropin-

Synthetic ACTH

Only used to assess hypothalamo-pituitary-adrenal axis
No therapeutic use/advantage over corticosteroids

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CRH action product

POMC

CRH diagnostic use

Differentiate pituitary and ectopic ACTH hypersecretion

Cortisol environmental factors

Morning
Light exposure
After meals

Factors raising CBG level

Pregnancy
Estrogen
Thyroid hormones

Cortisol metabolism

Hepatic: Cortisol -> Tetrahydrocortisol
Renal: Cortisol -> Cortisone -> Tetrahydrocortisone (liver)

Cortisol -receptor complex

Binds to GREs (glucocorticoid response elements)

Cortisol overall metabolic effect

Counter insulin

Cortisol specific metabolic effects

Increase:

Overal catabolism
Gluconeogenesis
Glycogen synthesis
Blood glucose
Hormone-sensitive lipase, lipolysis

Cortisol inflammatory effects

Anti-inflammatory/Immunosuppression

- Cytokines
- Capillary permeability (+ vasoconstriction)
- Leukocyte, lymphocyte responses

Cortisol calcium effects

``` Lower Ca levels -- Vit. D in the intestine -- Ca absorption ++ Ca clearance ++ Bone resorption ```

Addison's disease Tx

- Glucocorticoid replacement (daily hydrocortisone) | - Mineralocorticoid replacement

Impaired pituitary ACTH secretion Tx

- Glucocorticoid replacement only | - No ACTH or mineralocorticoid replacement

Congenital adrenal hyperplasia Tx

Due to defective cortisol synthesis, accompanied by elevated ACTH - Tx dexamethasone during gestation - Tx for acute insufficiency (IV hydrocortisone) after gestation

Cushing's syndrome Dx

Dexamethasone suppression test (negative feedback to pituitary ACTH)

Recommended administration for glucocorticoids

10 days, iatrogenic Cushing's afterwards

High dose glucocorticoid toxicity

Mineralocorticoid (HTN) effects | -Concern in heart disease patients

Prolonged glucocorticoid toxicity (4)

- Infection - Growth stunting - Catabolism (myopathy, osteoporosis, cataracts) - Adrenal suppression/atrophy

-Ketoconazole-

Inhibits P450 necessary for steroid synthesis | -Most effective, best tolerated Tx

-Metyrapone-

Inhibits CYP11B1 (11-hydroxylase) necessary for cortisol synthesis

-Mifepristone (RU486)-

Antagonist of glucocorticoid-R and progesterone-R | -Tx refractory Cushing's hyperglycemia

-Fludrocortisone-

Synthetic aldosterone (salt retaining)

Aldosterone stimulus

- Na depletion -> Angiotensin II - ACTH - Low Na or high K within the adrenal

Aldosterone action

Increase Na reabsorption in distal tubules, collecting ducts | -Increase K excretion

-Spironolactone-

Competitive mineralocorticoid-R (aldosterone) antagonist | -Tx primary aldosteronism