Adrenal Pharmacology

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Author:
Uchechi
ID:
30990
Filename:
Adrenal Pharmacology
Updated:
2010-08-23 21:43:03
Tags:
Cortisol Cushing\'s Addison\'s Adrenal
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Description:
Pharm for Adrenal deficiencies including cushing's and addison's
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  1. Why is corticosteroid-induced Cushing's syndrome more common in pts on ritonavir
    Because ritonavir inhibits CYP3A4 - enzyme involved in the metabolism of corticosteroids.
  2. Bone concerns for corticosteroid use?
    They can cause osteopenia/osteoporosis because they suppress bone remodeling and decrease calcium reabsorption.
  3. Caution on removing a pt from corticosteroids use
    • taper off!
    • Adrenal suppression makes this a must-do or the pt will crash
  4. Mechanism of action of Ketoconazole?
    - net effect of this mechanism?
    A Non-selective adrenal steroid synthesis inhibitor - to reduce cortisol levels

    net effect - all of aldosterone, cortisol and androgens will be reduced
  5. Concerns when using ketoconazole?
    CYP450 inhibitor. Major 3A4 inhibitor therefore hepatotoxicity is a major concern.

    Can have antiandrogenic effects since it reduced androgens too. i.e. gynecomastia in males
  6. Metyrapone - mechanism?
    Blocks 11B hydroxylase to decrease cortisol
  7. Concerns in using metyrapone?
    blocking 11Bhydroxylase causes the buildup of 11deoxycortisol which is an aldosterone receptor agonist - can therefore cause hypertension

    May also increase androgens - hirsutism in females
  8. Aminoglutethimide mechanism?
    Blocks rate-limiting conversion of cholesterol to prenenolone and increases steroid clearance.

    Non-selective and will decrease other adrenal hormones. Therefore it's often used in conjunction with metyrapone
  9. Mechanism of mitotane?
    Non-selective blocker of several steps in the synthesis of cortisol and aldosterone
  10. Side effects of Mitotane?
    Wipes out adrenal. Several. Also low TI, therefore only used as a 3rd line tx. Sometimes used in carcinomas and secondary cushing's like lung cancer if otherwise inoperable and other therapies fail
  11. Adverse effects of Aminogluthomide
    blocks thyroxine synthesis - hypothyroidism

    Induced CYP3A4 - possible drug interactions

    May be too effective in combo with metyrapone - adrenal insufficiency
  12. What is the mechanism of action of hydrocortisone?
    • activates glucocorticoid receptors??
    • Given in two doses to mimic natural cycle of cortisol
  13. What is the mechanism of action of fludrocortisone?
    • it's a hydrocortisone agonist. Specific for the aldosterone receptor.
    • It activates the mineralocorticoid receptor to increase the expression of the Na/K ATPase.

    Increases salt retention, and K excretion - necessary in Addison's if oral hydrocortisone has insufficient MR activity
  14. Adverse effect of Fludrocortisone?
    If the dose is too high, it can cause edema/hypertension, and hypokalemia.

    Hypokalemia predisposes pt to cardiac events

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