Steroidal Anti-inflammatory Drugs

Question 1

Describe the regulation of glucocorticoid secretion by the hypothalamic-pituitary-adrenal gland axis.

Answer 1

Hypothalamus releases CRH in response to sleep-wake cycles. Causes anterior pituitary to release ACTH, which stimulates to adrenal gland to release cortisol.

ACTH release from the ant. pituitary and CRH release from the hypothalamus is inhibited by negative feedback from circulating corticosteroids (by endogenous hormones and exogenous steroids used in therapy)

Stress can override negative feedback loop, and produce a marked increase in steroidogenesis.

Question 2

Describe the metabolic effects of glucocorticoids and explain how these effects can result in serious adverse conditions.

Answer 2

Carbohydrate: Stimulate gluconeogenesis (in fasting state)–> increase blood glucose–> increased insulin release. Stimulates gluconeogenesis and glycogen synthesis—> increased liver glycogen deposition.

Protein: Decreased protein synthesis, increased conversion of amino acids to glucose–> muscle wasting

Lipid: increase peripheral lipoylisis–> free fatty acids–> in excess : lipogenesis (centrally via insulin)–> centripetal obesity (buffalo hump, moon facies

Question 3

Hydrocortisone

Answer 3

Anti-inflammatory: Decreased production/action of cytokins; decreased expression of PGs (via COX2) and PGs and Leukotrieves via inhibition of PA2 (preventing formation of arachidonic acid).

Immunosuppressive: Suppress T cell activation, suppress cytokine production, prevent mast cells and eosinophils from releasing inhibitiory mediators.