SAR of Corticosteroids

Question 1

What essential functionality is there for anti-inflammation-

Answer 1

1. To bind to & activate a glucocorticoid receptor an oxygen at the 11-position is essential.
2. Can be in the form of a ketone(as in cortisone) or an alcohol (hydrocortisone/prednisolone)

Question 2

Describe the adrenal cortexes function - 3

Answer 2

1. Production & secretion of corticosteroids in response to pituitary gland signals (signalled by the hypothalamus).
2. Known as the hypothalamic pituitary adrenal axis (HPA).
3. Main endogenous corticosteroids - Hydrocortisone (cortisol) & corticosterone, with both mineralocorticoid & glucocorticoid activity.

Question 3

What is cholesterols role and how does it structure aid it - 4

Answer 3

1. Key structural features of naturally occurring glucocorticoid hormones
2. Conjugated ketone at C3: Important for receptor binding & defining hormone class
3. 11β-hydroxyl group (OH): Critical for anti-inflammatory activity & glucocorticoid receptor activation
4. 17β-ketol side chain: Distinguishes glucocorticoids from other steroids; contributes to hydrophilicity & specificity

Question 4

Glucocorticoids vs Mineralocorticoids- 6

Answer 4

Glucocorticoid:
1. Reduce inflammation & immune response
2. Redistributes fat
3. Hyperglycaemia

Mineralocorticoid:
4. Reabsorption of Na
5. Secretion of K & H
6. Increase BP & blood volume