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42 Cards in this Set

  • Front
  • Back
3 classes of steroids
Glucocorticoids
Mineralcorticoids
Weak androgens
Fxns of glucocorticoids
CHO metabolism
Protein metab
Lipid meta
Capillary permeability and vasomotor response
Almost everything else
Fxn of mineralcorticoids
Maintain electrolyte balance
What are the weak androgens?
Dehydroepiandrosterone
Androstenedione
*These are the major androgens in women
Biosynthesis of steroids
All from cholesterol
Cortisol and aldosterone have pregnenolone precursor
Why do cortisol and aldosterone have independent control if they have the same precursor?
Cortisol is synthesized in the zona fasiculata and reticularis
Aldosterone is made in the zona glomerulosa
Major regulatory substance of glucocorticoid synthesis
ACTH
How is ACTH regulated
By glucocorticoids and CRF (also under glucocorticoid control)
What controls aldosterone syn?
Angiotensin II
MA of steroids
Steroids bind GR alpha receptor--binds to cis and trans genes (alter rate of transcription)
GR beta
Alternative splice variant of GR, inhibits GR alpha action.
What does an increased GRbeta/GRalpha ratio appear to be responsible for?
Steroid-resistant asthma
12 therapeutic uses of adrenal steroids
Replacement Therapy
Anti-inflammatory
Asthma
Antiemesis
Pneumocystis carinii pneumo
Allergy
Fetal lung syndrome
Cerebral edema
Immunosuppression
Acute spinal cord injury
Cancer chemotherapy
Acute mountain illness
Common structure of all steroids
Pentanoperhydrophenanthrene ring
At physiologic levels, mineralcorticoid activity of glucocorticoids in mineralcorticoid target tissues is minimized how?
Inactivation of cortisol by 11-beta hydroxysteroid dehydrogenase (HSD 11B2)
At pharmocologic levels how is meneralcorticoid activity of glucocorticoids controlled?
Inactivation is insufficient so you get unwanted side effects.
*Synthetics take advantage of small structural differences to get around this
What increases glucocorticoid potency?
9 alpha fluoridation
1,2 double bond addition
What does CBG have to do w/availability?
Steroids that don't bind corticosteroid binding globulin have different 1/2 lives than those who do.
Metabolism of beflomethasone
More rapidly metabolized in lungs than glucocorticoids therefore elicit fewer systemic side effects.

Used to treat asthma
Fluticasone (flonase) and Budesonide
Undergo significant first pass metabolism
13 toxicities associated with adrenal steroids
Pituitary-adrenal suppression
Hypokalemia alkalosis, edema
Hyperglycemia (DM)
Increased infection
Inhibition of wound healing
Myopathy
Cushinoid effects
Antenatal neruotoxicity and
Small bowel perf
Behavioral disturbances
Peptic ulcer
Cataracts
Growth arrest in kids
Osteoporosis
How can we ameliorate osteoporosis caused by adrenal steroids?
Bisphosphonates: Aldendronate, etidronate, risedronate
Addison's dz
Adrenal insufficiency
Bronze diabetes, weakness, fatigue, anorexia, hypotension, hyponatremia, hyperkalemia
Apparent mineralcorticoid xs (inherited HTN)
mutant in HSD11B2 (kidney form of 11 beta hydroxysteroid dehydrogenase)

Decrease conversion of cortisol to cortisone
Condition similar to apparent mineralcorticoid xs.
Licorice poisoning--glycyrrhetinic acid (-) the enzyme
Congential Adrenal Hyperplasia
21-hydroxylase (salt wasting) or 11-hydroxylase (salt sparing) deficiency
Why is 11-hydroxylase deficiency salt sparing?
Compensation for aldosterone by 11-deoxycorticosterone
Cushing's
Hypercortisol
Conn's
Hyperaldosterone
Problem in hereditary primary cortisol resistance
Mutation in glucocorticoid receptor
Replacement therapy
5 mg prednisone in morning
Divided daily dose
Small dose in AM and PM to keep ACTH low and repress adrenal fxn, reducing production of weak adrenal androgens
Daily dose
Generally medium to high, suppress acute inflammatory disorders
Alternate day therapy
for patients in remission, minimize immunosuppressive side effects
Mifepristone
RU 486
Potent anti-glucorticoid
Early term abortions and stabilizing Cushing's
Spironolactone
Competitive inhibitor of aldosterone binding of mineralcorticoid receptor

Treats HTN and CHF
Eplerenone
Mineralcorticoid receptor antagonist

Treament of HTN and CHF
Dexamethasone
Inhibits ACTH and corticosteroid production
Mitotane
Analogue of DDT specific adrenocortical cells

Treat inoperable adrenal tumors
Metyrapone
Inhibits 11B-hydroxylation, glucocorticoid suppression, (-) of aldosterone syn.

Def. compensated by deoxycorticosterone
Aminoglutethimide
(-) first committed step in adrenal steroid biosynthesis: cholesterol-20a-hydroxycholesterol
Ketoconazole
Antifungal, inhibits side chain cleavage and 11B hydroxylase