Pharm 4 Adrenal Flashcards
5 layers of adrenal gland
Capsule Zona glomerulosa Zona fasiculata Zona reticularis Medulla
Zona glomerulosa - product, stimulus
Mineralocorticoids
-Angiotensin II, K+
Zona fasiculata - product, stimulus
Glucocorticoids, Androgens, Estrogens
-ACTH
Zona reticularis - product, stimulus
Glucocorticoids, Androgens, Estrogens
-ACTH
Medulla - product, stimulus
Epinephrine
-Sympathetic activation
3 Glucocorticoid drugs & duration
- Prednisone - short
- Triamcinolone - intermediate
- Dexamethasone - long
Glucocorticoid drug that is salt retaining
Prednisone
Glucocorticoid drug - strongest anti-inflammatory
Dexamethasone
Glucocorticoid drug - topical
Triamcinolone and dexamethasone
Prednisone activity
Inactive until hydroxylated to Prednisolone
Endogenous cortisol secretion inhibitors
GABA, opioids, cortisol
ACTH
Adrenocorticotrophic hormone
ACTH secretion
CRH -> POMC (pro-opiomelanocortin)
Adrenal steroid storage
None, secreted immediately
-Cosyntropin-
Synthetic ACTH
- Only used to assess hypothalamo-pituitary-adrenal axis
- No therapeutic use/advantage over corticosteroids
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
