Corticosteroid pharmacology Flashcards
(36 cards)
What is another name for cortisol?
Hydrocortisone.
When are cortisol levels highest?
In the morning.
When are cortisol levels at their lowest?
In the evening.
What corresponds to the circadian rhythm of cortisol?
The acetylation of glucocorticoid receptors (GR).
When are glucocorticoid receptors acetylated?
When cortisol levels are at their highest (morning).
When are glucocorticoid receptors de-acetylated?
When cortisol levels are at their lowest.
What is the affinity of glucocorticoid receptors when they are acetylated?
They have low affinity.
What is the affinity of glucocorticoid receptors when they are de-acetylated?
They have high affinity.
What acetylates glucocorticoid receptors?
CLOCK
When should glucocorticoid therapy (cortisone or hydrcortisone) be administered?
In the morning (no later than 9 AM).
Why should glucocorticoids be administered in the morning?
To mimic natural levels and to minimize adrenocortical suppression.
How does cortisol travel in the serum?
It is bound to corticosteroid-binding globulin (CBG).
What must be carefully monitored in children undergoing glucocorticoid therapy?
Growth must be carefully monitored.
What does the transcription factor CLOCK do?
It acetylates the glucocorticoid receptor which results in low target tissue sensitivity to glucocorticoids.
What is the long term stress response of mineralocorticoids?
The retention of sodium/water and increased blood pressure.
What is the long term stress response of glucocorticoids?
Hyperglycemia and immunosuppression.
How do glucocorticoids cause hyperglycemia?
Increased insulin resistance and increased gluconeogenesis (breakdown of fats/proteins and conversion to glucose).
What is the active metabolite of the prodrug prednisone?
Prednisolone.
What are four possible side effects of chronic glucocorticoid use?
Gluconeogenesis, osteoporosis, glaucoma, and depression.
What enzyme does the glucocorticoid receptor bind to causing histone de-acetylation (gene repression)?
HDAC2 (histone deacetylase 2).
What is fludrocortisone an agonist of?
Mineralocorticoid receptors.
What is the treatment for chronic adrenocortical insufficiency (Addison DIsease)?
Hydrocortisone and fludrocortisone given daily (glucocorticoid and mineralocorticoid replacement therapy).
What is the treatment for acute (i.e emergency) adrenocortical insufficiency?
Immediate treatment with IV hydrocortisone. Fludrocortisone is then given when hydrocortisone is reduced is reduced to the maintenance dose.
Why is hydrocortisone given as treatment for Addison disease (primary adrenocortical insufficiency)?
It activates both glucocorticoid receptors and mineralocorticoid receptors (mentioned in the Benoit cortex lecture).
