Adrenal Corticosteroids Flashcards

1
Q

What is most of the endogenous cortisol found bound to in the serum; how does this differ for biologically active cortisol?

A
  • Bound to proteins, corticosteroid-binding globulin (CBG) and albumin
  • Biologically active cortisol may be bound to erythrocytes
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2
Q

How do synthetic steroids differ from endogenous types in terms of binding to proteins in circulation?

A
  • Synthetic steroids other than prednisolone either bind weakly to albumin (2/3’s)

or

  • Circulate as free steroid (1/3)
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3
Q

In which tissues is the type 2 isoenzyme of 11β-hydroxysteroid-dehydrogenase found and what is its function?

A
  • Found mainly in mineralocorticoid target tissues (kidney, colon, salivary glands)

and

  • The placenta, in which it protects the cell from cortisol activation of the corticosteroid type 1 (mineralocorticoid) receptor
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4
Q

Why does prednisone have less salt-retaining activity compared to cortisol?

A

Prednison is more effectively oxidized by 11β-hydroxysteroid-dehydrogenase type 2

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5
Q

Which CYP is responsible for the metabolism of synthetic and natural glucocorticoids?

A

CYP3A4

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6
Q

How does the 11β-hydroxysteroid-dehydrogenase type 1 vs. type 2 isoenzyme differ in their action on steroids?

A
  • Type 2 converts active steroids –> inert forms
  • Type 1 converts inert steroids –> active forms
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7
Q

What are the active forms of cortisone, 11-dehydrocorticosterone, and prednisone; which enzyme activates them?

A
  • Cortisone —> cortisol (active)
  • 11-dehydrocorticosterone –> corticosterone (active)
  • Prednisone —> prednisolone (active)

*All due to 11β-hydroxysteroid-dehydrogenase type 1*

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8
Q

What are known inhibitors of 11β-hydroxysteroid-dehydrogenase type 2?

A
  • Glycyrrhizin (licorice root extract)
  • Carbenoxolone (UK approved for Rx-esophageal ulcers)
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9
Q

What is the downstream effect following inhibition of 11β-hydroxysteroid-dehydrogenase type 2 by substances such as glycyrrhizin (licorice root extract)?

A

↑ activity cortisol 2 MR –> ↑ Na+ and H2O retention, ↑ K+ loss –> ↑ BP

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10
Q

List 5 ways that glucocorticoids effect the immune system and inlammation

A
  • ↓ production of prostaglandins and leukotrienes
  • ↓ production and ↑ apoptosis of immune cell types
  • ↓ production of cytokines + their receptors
  • ↓ transmigration of neutrophils and macrophages from blood –> tissue
  • ↓ expression of cell adhesion molecules
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11
Q

Which combination of corticosteroids can be given for primary adrenal insufficiency and congenital adrenal hyperplasia?

A

Hydrocortisone + Fludrocortisone

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12
Q

List the 5 short to medium acting glucocorticoids (<12 hours)?

A
  • Hydrocortisone (cortisol)
  • Cortisone
  • Prednisone
  • Prednisolone
  • Methylprednisolone
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13
Q

What is the intermediate-acting (12-36 hour) glucocorticoid?

A

Triamcinolone

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14
Q

List the 2 long-acting (>36 hours) glucocorticoids.

A
  • Betamethasone
  • Dexamethasone
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15
Q

List 7 AE’s associated with prednisolone use.

A
  • Adrenal suppression
  • Growth inhibition
  • Muscle wasting
  • Osteoporosis
  • Salt retention
  • Glucose intolerance
  • Behavioral changes
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16
Q

Which drug is a glucocorticoid receptor antagonist and which receptors does it act on?

A
  • Mifepristone
  • Antagonist of glucocorticoid and progesterone receptors
17
Q

What are the clinical uses of Mifepristone?

A
  • Medical abortion
  • Very rarely for Cushing’s Syndrome
18
Q

Which 2 short to medium acting corticosteroids have the most potent anti-inflammatory activity and are available in a topical formula?

A
  • Prednisolone
  • Methylprednisolone
19
Q

Of the long-acting corticosteroids which is the most potent anti-inflammatory drug?

A

Dexamethasone

20
Q

What is the name of the mineralocorticoid agonist used clincially and what is its anti-inflammatory vs. salt-retaining potency like?

A
  • Fludrocortisone
  • Mild anti-inflammatory potency w/ ↑↑↑ salt-retaining activity
21
Q

List the AE’s associated with mifepristone.

A
  • Vaginal bleeding in women
  • Abdominal pain + GI upset
  • Diarrhea
  • HA
22
Q

What is the clinical application for Fludrocortisone?

A

Adrenal insufficiency (Addison’s disease)

23
Q

What is the duration of action like for Fludrocortisone?

A

Long

24
Q

What are 3 AE’s associated with Fludrocortisone?

A
  • Salt and fluid retention
  • CHF
  • Signs and sx’s of glucocorticoid excess
25
Q

What is the name of the mineralocorticoid receptor antagonist?

A

Spironolactone

26
Q

What are the clinical applications of Spironolactone?

A
  • Hyperaldosteronism from any cause
  • Hypokalemia due to diuretic effect
  • Post-MI
27
Q

What is the onset of action and duration like for Spironolactone?

A

Slow onset and offset; duration = 24-48 hrs

28
Q

What are the AE’s and drug-interactions associated with Spironolactone?

A
  • HYPERkalemia
  • Gynecomastia
  • Additive interaction w/ other K+ retaining drugs