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Week 51 > Dewitt: Adrenal > Flashcards

Flashcards in Dewitt: Adrenal Deck (24)
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1

Corticosteroids: Agonists and Antagonists

  • Agonists:
    • Glucocorticoids
      • prednisode
    • Mineralcorticoids
      • fludrocortisone
  • Antagnoists:
    • Synthesis inhibitors:
      • Ketoconazole
    • Receptor Antagonists:
      • Glucocorticoid antagonists:
        • mifepristone
      • Mineralocorticoid antagonists:
        • apironolactone

2

Adrenal Hormone Pathway

  • Negative feedback: Androgens, glucocorticoids, mineralocorticoids

3

What zone of the adrenal gland does mineralocorticoids, glucocorticoids, and androgens come from?

  • Mineralocorticoids:
    • zona glomerulosa (outer)
      • Major: Aldosterone
      • minor=deoxycorticosterone
  • Glucocorticoids:
    • zona fasciculata
      • major=cortisol
  • Androgens
    • Zona reticularis (inner)

4

Clinical Presentation of Low mineralocorticoids

  • Addison's Disease=chronic adrenal insufficiency
    • low aldosterone
      • low blood pressure
      • salt craving

5

Pharmacological management of Low mineralocorticosteroid?

  • cosyntropin/ACTH
  • Fludrocortisone

6

Cosyntropin

  • Low mineralocorticoids or glucocorticoids
  • diagnose if adrenal insufficiency is:
    • primary-adrenal
    • Secondary=pituitary
    • Tertiary=Hypothalamus

7

Fludorocortisone

  • Low mineralocorticosteroid (Addison's Disease)
  • Synthetic corticosteroid 
  • Mechanism=cortisol Agonist (w/salt retaining activity)
  • most widely used mineralocorticoid
    • Long duration of action
    • potent corticosteroid
    • High salt-retaining activity
    • Glucocorticoid activity
      • low doses-no anti-inflammatory or anti-growth effects

8

Desoxycorticosterone acetate

  • Salt retaining agent w/no anti-inflammatory 
  • Not in US

9

Clinical Presentaiton of High mineralocorticoids

  • Cushing Syndrome or Primary Aldosteronism
    • adrenal hypersecretion 
      • High aldosterone
    • hypertension/edema

10

Pharmacological management of High Mineralocorticoids?

  • Aldosterone Antagonist
    • Spironolactone
    • Eplerenone
    • Drospirenone

11

Spironolactone

  • High Mineralocorticoids (aldosterone)
  • Aldosterone antagonist: 
    • does not reduce aldosterone production
    • also:
      • androgen antagonist
      • progesterone agonist
  • used to tx primary aldosteronism or higher doses to diagnose aldosteronism
  • Side effects:
    • breast tenderness
    • irregular menstrual cycles
    • impotence
    • decreased libido
    • gynecomastia in men

12

Eplerenone

  • Aldosterone Antagonist
  • more selective than spironolactone
    • Not a androgen antagonist

13

Drospirenone

  • Progestin
  • Aldosterone antagonist

14

Pharmacological management of low glucocorticoids

 

  • Hydrocortisone
    • may need fludrocortisone depending on degree of adrenal insufficiency

15

Hydrocortisone

  • cortisol agonists
  • most common glucocorticoid for low glucocorticoid
  • some salt retaining activity
    • but may need fludrocortisone depending on degree of adrenal insufficiency (in primary insufficiency)
  • Given in large amounts (IV) for:
    • acute adrenal insufficiency
    • congenital adrenal hyperplasia 
      • (Fludrocortison given for low mineralocorticoid production)

16

Dexamethasone

  • Synthetic Cortisol
  • Pregnancies at high risk for congenital adrenal hyperplasia
  • protect fetus 

17

Pharmacological management of high glucocorticoids

  • Synthesis inihibitors:
    • Aminoglutethimide
    • Ketoconazole
    • Etomidate
    • Metyrapone
  • Mifepristone
  • Mitotane

18

Synthesis of glucocorticoids

  • multistep rpcoess 
  • many adrenal hormones share common pathways/starting products

19

Aminoglutethimide

  • High Glucocorticoids
  • Mechanism: Cortisol Synthesis Inhibitors
  • Blocks conversion of Cholesterol to prenenolone
    • reduces synthesis of all hormon active steroids
  • Tx: Cushing's Syndrome

20

Ketoconazole

  • Antifungal Agent
  • Mechanism=Cortisol synthesis inhibitors
  • inhibits cholesterol side chain cleavage 
  • Tx: Cushing's Syndrome
  • Side effect:
    • hepatotoxicity

21

Etomidate

  • Mechanism: Cortisol Synthesis Inhibitors
  • Inhibits adrenal steroidogenesis
  • ONLY parenteral agent for Cushings Syndrome

22

Metyrapone

  • Mechanism: Cortisol Synthesis Inhibitors:
  • Selective inhibitor of specific enzyme in cortisol synthesis pathway
  • Tx: Cushing's Syndrome
  • No longer in US except on compassionate basis

23

Mifepristone (RU-486)

  • Mechanism: Cortisol Antagonist
  • Glucocorticoid Antagonist
  • can cause generalized glucocorticoid resistance
  • Tx: Only inoperable ectopic ACTH secretion or adrenal carcinoma
    • failed to respond to other agents
    • Due to: 
      • long Half life
      • Widespread receptor antagonism

24

Mitotane

  • Mechanism: Cytotoxic to adrenal cortex
    • nonselective cytotoxic on adrenal cortex to reduce tumors
  • Removed from US market
    • available on compassinate basis