Pharm Final: Adrenocortical Hormones
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Pharm Final: Adrenocortical Hormones
HPA axis controls body processes, DIMES. Define.
Which stress response is RAPID?
SNS (NE/Epi) versus HPA (fast not rapid)
What are the ultimate effects of glucocorticoids, mineralcorticoids, & androgens?
: immune system/ metabolism (cortisol)
: salt retaining (aldosterone)
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
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?
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
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?
: PUD (H. pylori overgrowth)
: redistribution (buffalo hump)
: Antagonism (impaired CA absorption)
: 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
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?
-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?
-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)
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
3. Androgen antagonist (for Hirsutism)
What are some S/E of Spironolactone?
-menstrual abnormality, gynecomastia
-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?
2. Mefepristone (RU-486)
-High vs low dose
-Antifungal in low doses
-Non-selective inhibition of adrenal/gonadal steroid synthesis (high doses)
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?
2. skin rash
3. Decrease stress tolerance (accelerates steroid clearance)
4. Enhances metabolism of Dex