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42 Cards in this Set
- Front
- Back
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3 classes of steroids
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Glucocorticoids
Mineralcorticoids Weak androgens |
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Fxns of glucocorticoids
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CHO metabolism
Protein metab Lipid meta Capillary permeability and vasomotor response Almost everything else |
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Fxn of mineralcorticoids
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Maintain electrolyte balance
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What are the weak androgens?
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Dehydroepiandrosterone
Androstenedione *These are the major androgens in women |
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Biosynthesis of steroids
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All from cholesterol
Cortisol and aldosterone have pregnenolone precursor |
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Why do cortisol and aldosterone have independent control if they have the same precursor?
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Cortisol is synthesized in the zona fasiculata and reticularis
Aldosterone is made in the zona glomerulosa |
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Major regulatory substance of glucocorticoid synthesis
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ACTH
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How is ACTH regulated
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By glucocorticoids and CRF (also under glucocorticoid control)
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What controls aldosterone syn?
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Angiotensin II
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MA of steroids
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Steroids bind GR alpha receptor--binds to cis and trans genes (alter rate of transcription)
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GR beta
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Alternative splice variant of GR, inhibits GR alpha action.
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What does an increased GRbeta/GRalpha ratio appear to be responsible for?
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Steroid-resistant asthma
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12 therapeutic uses of adrenal steroids
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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 |
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Common structure of all steroids
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Pentanoperhydrophenanthrene ring
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At physiologic levels, mineralcorticoid activity of glucocorticoids in mineralcorticoid target tissues is minimized how?
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Inactivation of cortisol by 11-beta hydroxysteroid dehydrogenase (HSD 11B2)
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At pharmocologic levels how is meneralcorticoid activity of glucocorticoids controlled?
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Inactivation is insufficient so you get unwanted side effects.
*Synthetics take advantage of small structural differences to get around this |
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What increases glucocorticoid potency?
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9 alpha fluoridation
1,2 double bond addition |
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What does CBG have to do w/availability?
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Steroids that don't bind corticosteroid binding globulin have different 1/2 lives than those who do.
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Metabolism of beflomethasone
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More rapidly metabolized in lungs than glucocorticoids therefore elicit fewer systemic side effects.
Used to treat asthma |
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Fluticasone (flonase) and Budesonide
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Undergo significant first pass metabolism
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13 toxicities associated with adrenal steroids
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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 |
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How can we ameliorate osteoporosis caused by adrenal steroids?
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Bisphosphonates: Aldendronate, etidronate, risedronate
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Addison's dz
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Adrenal insufficiency
Bronze diabetes, weakness, fatigue, anorexia, hypotension, hyponatremia, hyperkalemia |
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Apparent mineralcorticoid xs (inherited HTN)
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mutant in HSD11B2 (kidney form of 11 beta hydroxysteroid dehydrogenase)
Decrease conversion of cortisol to cortisone |
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Condition similar to apparent mineralcorticoid xs.
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Licorice poisoning--glycyrrhetinic acid (-) the enzyme
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Congential Adrenal Hyperplasia
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21-hydroxylase (salt wasting) or 11-hydroxylase (salt sparing) deficiency
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Why is 11-hydroxylase deficiency salt sparing?
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Compensation for aldosterone by 11-deoxycorticosterone
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Cushing's
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Hypercortisol
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Conn's
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Hyperaldosterone
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Problem in hereditary primary cortisol resistance
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Mutation in glucocorticoid receptor
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Replacement therapy
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5 mg prednisone in morning
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Divided daily dose
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Small dose in AM and PM to keep ACTH low and repress adrenal fxn, reducing production of weak adrenal androgens
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Daily dose
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Generally medium to high, suppress acute inflammatory disorders
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Alternate day therapy
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for patients in remission, minimize immunosuppressive side effects
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Mifepristone
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RU 486
Potent anti-glucorticoid Early term abortions and stabilizing Cushing's |
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Spironolactone
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Competitive inhibitor of aldosterone binding of mineralcorticoid receptor
Treats HTN and CHF |
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Eplerenone
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Mineralcorticoid receptor antagonist
Treament of HTN and CHF |
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Dexamethasone
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Inhibits ACTH and corticosteroid production
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Mitotane
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Analogue of DDT specific adrenocortical cells
Treat inoperable adrenal tumors |
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Metyrapone
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Inhibits 11B-hydroxylation, glucocorticoid suppression, (-) of aldosterone syn.
Def. compensated by deoxycorticosterone |
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Aminoglutethimide
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(-) first committed step in adrenal steroid biosynthesis: cholesterol-20a-hydroxycholesterol
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Ketoconazole
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Antifungal, inhibits side chain cleavage and 11B hydroxylase
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