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Endo-Repro I > Corticosteroid pharmacology > Flashcards

Corticosteroid pharmacology Flashcards

1
Q

What is another name for cortisol?

A

Hydrocortisone.

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2
Q

When are cortisol levels highest?

A

In the morning.

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3
Q

When are cortisol levels at their lowest?

A

In the evening.

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4
Q

What corresponds to the circadian rhythm of cortisol?

A

The acetylation of glucocorticoid receptors (GR).

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5
Q

When are glucocorticoid receptors acetylated?

A

When cortisol levels are at their highest (morning).

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6
Q

When are glucocorticoid receptors de-acetylated?

A

When cortisol levels are at their lowest.

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7
Q

What is the affinity of glucocorticoid receptors when they are acetylated?

A

They have low affinity.

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8
Q

What is the affinity of glucocorticoid receptors when they are de-acetylated?

A

They have high affinity.

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9
Q

What acetylates glucocorticoid receptors?

A

CLOCK

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10
Q

When should glucocorticoid therapy (cortisone or hydrcortisone) be administered?

A

In the morning (no later than 9 AM).

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11
Q

Why should glucocorticoids be administered in the morning?

A

To mimic natural levels and to minimize adrenocortical suppression.

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12
Q

How does cortisol travel in the serum?

A

It is bound to corticosteroid-binding globulin (CBG).

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13
Q

What must be carefully monitored in children undergoing glucocorticoid therapy?

A

Growth must be carefully monitored.

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14
Q

What does the transcription factor CLOCK do?

A

It acetylates the glucocorticoid receptor which results in low target tissue sensitivity to glucocorticoids.

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15
Q

What is the long term stress response of mineralocorticoids?

A

The retention of sodium/water and increased blood pressure.

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16
Q

What is the long term stress response of glucocorticoids?

A

Hyperglycemia and immunosuppression.

17
Q

How do glucocorticoids cause hyperglycemia?

A

Increased insulin resistance and increased gluconeogenesis (breakdown of fats/proteins and conversion to glucose).

18
Q

What is the active metabolite of the prodrug prednisone?

A

Prednisolone.

19
Q

What are four possible side effects of chronic glucocorticoid use?

A

Gluconeogenesis, osteoporosis, glaucoma, and depression.

20
Q

What enzyme does the glucocorticoid receptor bind to causing histone de-acetylation (gene repression)?

A

HDAC2 (histone deacetylase 2).

21
Q

What is fludrocortisone an agonist of?

A

Mineralocorticoid receptors.

22
Q

What is the treatment for chronic adrenocortical insufficiency (Addison DIsease)?

A

Hydrocortisone and fludrocortisone given daily (glucocorticoid and mineralocorticoid replacement therapy).

23
Q

What is the treatment for acute (i.e emergency) adrenocortical insufficiency?

A

Immediate treatment with IV hydrocortisone. Fludrocortisone is then given when hydrocortisone is reduced is reduced to the maintenance dose.

24
Q

Why is hydrocortisone given as treatment for Addison disease (primary adrenocortical insufficiency)?

A

It activates both glucocorticoid receptors and mineralocorticoid receptors (mentioned in the Benoit cortex lecture).

25
Q

What is the treatment for Cushing syndrome?

A

Ketoconazole, followed by pituitary tumor removal, radiation, or adrenal resection.

26
Q

What is the treatment plan for Cushing syndrome after surgery?

A

Large dose of hydrocortisone is given which is gradually reduced.

27
Q

What is Chrousos syndrome?

A

Primary generalized glucocorticoid resistance.

28
Q

What causes Chrousos syndrome?

A

An inactivating mutation in the glucocorticoid receptor.

29
Q

What does Chrousos syndrome present with in terms of ACTH and cortisol levels?

A

Both ACTH and Cortisol levels are elevated (body is trying to make a cortisol response but the receptors are bust).

30
Q

What else does Chrousos syndrome present with?

A

Mineralocorticoid excess, such as 11-deoxycorticosterone (hypokalemic alkalosis).

31
Q

What is the treatment for Chrousos syndrome?

A

Dexamethasone (lacks mineralocorticoid activity).

32
Q

What does hyper-aldosteronism present with?

A

Hypertension, decreased renin (negative feedback from the increased serum osmolarity), hypokalemia (alkalosis),

33
Q

What is the treatment for hyper-aldosteronism?

A

Aldosterone receptor antogonists (spironolactone and eplerenone).

34
Q

What does abrupt cessation of long term corticosteroid use cause?

A

Corticosteroid withdrawal syndrome.

35
Q

How can corticosteroid withdrawal syndrome be avoided?

A

By gradually reducing the dose of corticosteroids.

36
Q

What is an example of a glucocorticoid receptor antagonist?

A

Mifepristone.

Endo-Repro I (12 decks)

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