Term
| Most circulating cortisol is ___, which is synthesized by ___ and increased by ___ |
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Definition
Bound to CBG
Liver
Increases by estrogen and pregnancy |
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Term
| Synthetic glucocorticoids are bound to ___ |
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Definition
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Term
| Cortisol enhances gene expression for (3) |
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Definition
Lipocortin: inhibits phospholipase A2
Gluconeognesis enzymes
Glycogen synthetase |
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Term
| Cortisol inhibits gene expression of (5) |
|
Definition
HT CRH
Pit POMC
Leukocyte COX2
Macro IL1, 6, TNF, collagenase
GLUT2 = inhibited peripheral uptake of glucose |
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Term
| (Permissive) physiological effects of glucocorticoids (5) |
|
Definition
Contraction of skeletal muscle
Contraction of vascular smooth muscle
Relaxation of bronchial smooth muscle
Induction of lipolysis
Maintain GFR and C-H2O |
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Term
| Cortisol maintains glucose for ___ even if it means ___ |
|
Definition
The brain
Destroying other tissues |
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Term
| Lipid metabolism in hypercortisolism |
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Definition
Redistribution of fat from extremities to thorax and abdomen
-Peripheral fat cells respond to cortisol = lipolysis
-Truncal fat cells respond to insulin = fat storage |
|
|
Term
| Pathogenesis of the red striae |
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Definition
| Catabolic effects on lymphoid and connective tissue, muscle, fat, skin |
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Term
| Cortisol effects on bone (4) and marrow (1) |
|
Definition
Inhibit osteoblasts
Indirectly stimulate PTH and osteoclast activity
-Inhibit Ca absorption
-Increase Ca excretion
Avascular necrosis of femoral head
Even small doses can reduce linear growth in kids
Stimulates erythropoiesis |
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|
Term
| Why cortisol works for immunosuppression |
|
Definition
Decrease circulating lymphocytes, mono, eos, basos
Inhibit leukocyte, macro responses
Inhibit Ab production |
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Term
| Decreased cortisol can cause CNS effects like ___, ___, ___ |
|
Definition
Apathy
Depression
Irritability |
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|
Term
| Cortisol's effect on HT-release of other hormones |
|
Definition
| Inhibits TRH and GnRH release |
|
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Term
| Cortisol stimulates fetal production of ___ |
|
Definition
|
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Term
| Glucocorticoids: formulations and methods of admin, t1/2 |
|
Definition
Phosphate and succinate Na esters: water-soluble, rapid absorption post IM or subcu
Acetate: low water solubility, prolonged effect after subcu and joints (no IV!)
Short: 8-12h
-Cortisone
-Hydrocortisone
Intermediate: 12-36h (alternate day tx)
-Methylprednisolone
-Prednisolone
-Prednisone
-Triam
Long: 36-72h
-Beta
-Dex |
|
|
Term
| Greatest anti-inflamm and longest duration (2) |
|
Definition
|
|
Term
| Greatest mineralocorticoid activity (1) |
|
Definition
|
|
Term
| Glucocorticoids: indications (6) |
|
Definition
Adrenal insufficiency
Addison's
Fetal lung maturation
CAH
Dexamethasone suppression test for dx Cushing's
Surgery in patients with hypercortisolism |
|
|
Term
| Acute adrenal insufficiency tx (1) |
|
Definition
| Hydrocortisone (fluids, electrolytes too) |
|
|
Term
|
Definition
Hydro/cortisone + fludro
Required for life, gotta be increased during stress |
|
|
Term
|
Definition
|
|
Term
| Fetal lung maturation tx (1) |
|
Definition
|
|
Term
| Glucocorticoids: S/E categories (3), desired dose |
|
Definition
Adrenal suppression
Iatrogenic Cushing's syndrome
Drug-drug interactions
Dose as small as you can! |
|
|
Term
| Adrenal suppression S/E (3), timing (2) |
|
Definition
Acute adrenal insufficiency
Reappearance of inflammatory disease
Malaise, myalgia, arthralgia, fever
4-7 days after treatment, recovery usually prompt
Short-term: descending dose pack
Prolonged: withdraw the drug slowly
-Adrenals responsive after 2-3 mo
-Normal by another 6-9 mo |
|
|
Term
| Iatrogenic Cushing's syndrome S/E (PREDNISONE) |
|
Definition
Peptic ulcers
Retention of salt/water, hypoK, hypoCl, alkalosis, HTN
Extra fat
Diabetes
Neurosis, psychosis
Infections
Suppression of pit-adrenal axis
Osteoporosis: 30-50%, especially ribs and vertebrae
Negative nitrogen balance, muscle wasting
Eye posterior subcapsular cataracts and glaucoma |
|
|
Term
| Drug-drug interactions (2) |
|
Definition
CYP450 induces enhance metabolism of the steroids
Furosemide and HCTZ enhance the hypokalemia |
|
|
Term
| Alternate day tx: rationale, additional drugs/things to do |
|
Definition
Max effect with minimal suppression of HT-pit axis
K supplements: prevent mineralo hypoK
High protein diet, maybe anabolic steroids: counteract muscle wasting
Diet and insulin: control hyperglycemia
vitD, Ca supplement, bisphosphonates: prevent osteoporosis
Periodic exam to detect cataracts and measure IOP |
|
|
Term
|
Definition
Alendronate
Ibandronate
Both are 2nd generation |
|
|
Term
| Bisphosphonates: MOA (2), dosing |
|
Definition
Retard osteoclastic dissolution of hydroxyapetite crystals = prevent resorption
May increase osteoblast activity
p.o. + empty stomach + 8-10 oz water + upright for 30 min (bioavailability is horrible!) |
|
|
Term
| Bisphosphonates: indications (3), contraindications, S/E |
|
Definition
Indications
-Steroid-induced and post-menopausal osteoporosis
-Paget's disease
-Cancer-associated hyperCa
Contraindications
-Esophageal motility issues
-Peptic ulcer disease
-Decreased renal function
Osteonecrosis of the jaw (IV + previous insult) |
|
|
Term
| Aminogluthethimide: MOA, physiologic effects |
|
Definition
Inhibits CYP450 conversion of C to pregnenolone and extra-adrenal aromatase
Blocks all adrenal and extra-adrenal steroid synthesis = medical adrenalectomy
Body increases ACTH secretion, so gotta give hydrocortisone or dex to suppress this compensatory mechanism |
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|
Term
| Aminogluthethimide: indications (2) |
|
Definition
Suppress sex steroid synthesis in breast cancer (gotta add dex)
Tx adrenal carcinoma causing Cushing's syndrome |
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