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HPA axis controls body processes, DIMES. Define.
- M- Mood
- E-Energy stores
- S- sexuality
Which stress response is RAPID?
SNS (NE/Epi) versus HPA (fast not rapid)
What are the ultimate effects of glucocorticoids, mineralcorticoids, & androgens?
- Glucocorticoids: immune system/ metabolism (cortisol)
- -Mineralocorticoids: salt retaining (aldosterone)
- -Androgen: DHEA
List 7 effects of gluco-corticoids (acute)?
- 1. ⇑ gluconeogenesis
- 2. ⇑ Lipolysis
- 3. ⇑ arousal
- 4. ⇑ BP
- 5.⇑ fuel from skeletal muscle
- 6. ⇓ wound healing
- 7. ⇓ inflammation
8 effects of chronic stress
- 1. lymphocyte suppression--> infection
- 2. glucose alteration --> DM
- 3. HTN
- 4. Bone resorption
- 5. Ca+ absorption inhibition
- 6. Gonadotropin inhibition
- 7. Fat accumulation/redistribution
- 8. Increase renal vasopressin activity
What are 4 effects of cortisol?
- 1. metabolism
- 2. CV
- 3. growth
- 4. immunity
When does ACTH pulses peak?
Early AM & after meals
T or F. During fight or flight, catecholamines effects are "blunted" without cortisol.
True because cortisol enhances the response. Also enhances lipolytic response of fat cells to catecholamines
T or F. Cortisol counteracts insulin.
True. causing insulin resistance (increasing available glucose)
T or F. Cortisol has an anabolic effect of protein synthesis.
False--> catabolic--> stimulates protein synthesis in liver BUT degrades proteins in lymph, connective tissue, muscle, peripheral, fat & skin
How does cortisol have an anti-inflammatory effect?
- -Decrease leukocyte function
- -Decrease cytokines, chemokines, & mediators
- -Inhibits macrophages
- -Decrease COX-2
- -Decrease prostaglandins
What is the effect of one dose of glucocorticoids?
- 1. Increase circulating neutrophils
- 2. Decrease circulating lymph (T&B)
- -Max effect 6 hrs
Decrease cortisol in the CNS causes what?
- -Slowed alpha rhythm on EEG
- -Associated w/ depression
What are the effects of high doses of cortisol in the CNS?
- 1. Insomnia, euphoria--> depression
- 2. Increased ICP
- 3. Chronic exposure: pituitary suppression (decrease ACTH, GH, TSH, LH)
What are the effects of excess cortisol on GI, fat, Vit D, Heme?
- GI: PUD (H. pylori overgrowth)
- Fat: redistribution (buffalo hump)
- Vit D: Antagonism (impaired CA absorption)
- Heme: Increase platelets and RBCs
- ** important for fetal lung maturity
T or F. Synthetic corticosteroids are rapidly & completely absorbed.
Where does synthetic corticoids bind?
Intracellular receptor proteins
How is synthetic cortisol used in diagnostics?
- -Suppress ACTH to identify a hormone & if production is due to ACTH
- --> Dex suppression test (Cushing's diag vs depression
- -R/o tumor or ectopic ACTH syndrome
With Dex test, what level is normal and what is considered Cushings?
- Normal < 3mcg/dl
- Cushings >5mcg/dl
List 4 common therapeutic uses of synthetic cortisol?
- 1. Adrenocortical insufficiency (addison's)
- 2. Adrenocortical hypo/hyper function (CAH, Cushings, Aldosteronism)
- 3. Fetal lung maturity
- 4. Nonadrenal disorders (transplant rejection)
- 5. Immuno problems
- 6. Lots others
What are some toxic effects of cortisol?
- -metabolic (glucose)
- -Depression (long term)
- -Eye (cataracts, glaucoma)
- -growth retardation in children
- -Mineralcorticoid effects (Na/fluid retention, K+ loss)--> HF
When can adrenal suppression occur when taking cortisol?
- -> 2weeks
- -wean 2-12mo for normal HPA axis
- -Takes 6-9mo for cortisol levels to normalize
List 6 contraindications of cortisol?
- 1. PUD, CVD, HTN
- 2. Infections (varicella & TB)
- 3. Psych
- 4. DM
- 5. Osteoporisis
- 6. glaucoma
If you want to increase androgen levels, where should you start?
ACTH (start at tip--> pituitary)
What is Fludrocortison?
Synthetic aldosterone--> most commonly prescribed salt-retaining hormone
What is the precursor to aldosterone?
Deoxycorticosterone, primarily controlled by ACTH, 1/2life-->70min
T or F. Fludrocortisone has very little anti-inflammatory or anti-growth impact.
True (potent salt retaining)
What drug is a mineralocorticoid antagonist and when is it used?
- 1. Primary aldosteronism (reverses manifestations, establishes diagnosis,relieves pre-operative symptoms
- 2. Diuretic
- 3. Androgen antagonist (for Hirsutism)
What are some S/E of Spironolactone?
- -menstrual abnormality, gynecomastia
- -sedation, H/A
- -GI upset
- -Skin rash
- -Mineralocorticoid antagonist
- -more selective than spironolactone
- -NO impact on androgen receptors
T or F. Adrenal androgen stimulate puberty.
FALSE--> contributes but doesn't stimulate
What is the effect of adrenal androgens on lupus and adrenal insufficiency?
- Lupus--> improves disease
- Adrenal insufficiency--> enhanced well-being
Name 3 Androgen SYNTHESIS inhibitors?
- 1. Ketoconazole
- 2. Mefepristone (RU-486)
- 3. Aminoglutethimide
-High vs low dose
- -Antifungal in low doses
- -Non-selective inhibition of adrenal/gonadal steroid synthesis (high doses)
- -P450 pathway
- -Cushings syndrome
T or F. Mifepristone is an ENZYME inhibitor.
FALSE, androgen SYNTHESIS inhibitor
T or F. Mifepristone binds to CBG not albumin.
FALSE (RU-486 binds to albumin NOT CBG)
What are the 2 current recommendations for RU-486?
- 1. Non-operable disease (ectopic ACTH prod)
- 2. Adrenal CA non-responsive to other therapy
-Blocks conversion of cholesterol to pregnolone (decrease steroid production)
What are 2 uses for Aminoglutethimide?
- 1. Hormone + Br Ca (but replaced by Tamoxifen)
- 2. Cushing syndrom
What are 4 S/E or cautions for Aminoglutethimide?
- 1. Lethargy
- 2. skin rash
- 3. Decrease stress tolerance (accelerates steroid clearance)
- 4. Enhances metabolism of Dex