1. Adrenocorticosteroids พญ. มาลียา มโนรถ

2. Adrenocorticosteroids Emotional stress Hypothalamus CRF Anterior pituitary gland ACTH Adrenal cortex Adrenal steroids Diurnal rhythms Trauma negative inhibition

3. Adrenocorticosteroids Glucocorticoids – important effects on intermediary metabolism Mineralocorticoids – salt-retaining activity Sex hormones – androgenic or estrogenic activity

4. Glucocorticoids Natural steroids –cortisol (hydrocortisone) –cortisone –corticosterone Synthetic steroids –prednisolone –triamcinolone

5. Corticosteroid secretion : diurnal rhythm Stress : tenfold CortisolAldosterone Rate of secretion under optimal condition10 mg/d0.125 mg/d Concentration in peripheral plasma 8 a.m.16 g/100 ml0.01 g/100 ml 4 p.m. 4 g/ml0.01 g/ml

6. Pharmacokinetics Natural : adrenal glands Synthetic : cholic acid, plants PO : rapidly & completely absorbed Bound to plasma protein (CBG) Metabolized : liver T 1/2 of cortisol 60-90 min

7. Mechanism of action H + R (cytosolic receptor) HRC GREs (glucorticorticoid response element : nucleus) Expression hsp 90

8. Glucocorticoid effects Influence the function of most cells ญ Liver glycogen deposition ญ Gluconeogenesis ญ Protein catabolism ญ Bone catabolism ฏ Inflammatory responses ฏ Immunological responses

9. Relative potencies of corticosteroids Na + Anti-inflammatory retention effect Natural steroids Cortisol11 Aldosterone3,000? Synthetic steroids Prednisolone0.254 Triamcinolone< 0.015 Betamethasone< 0.0125 Dexamethasone< 0.0130-40

10. Beclomethasone Budesonide readily penetrate the airway mucosa but have very short half-life after enter the blood

11. Topical activity Glucocorticoids Cortisol0 Prednisolone+/- Triamcinolone+++ Dexamethasone+++++ Mineralocorticoids Aldosterone0 Fludrocortisone0

12. Adverse Reactions Hyperglycemia (DM occasionally) Protein loss muscle wasting Bone catabolism : osteoporosis Fluid retention Adrenal suppression Infections

13. Clinical Uses Substitution therapy acute adrenal insufficiency Nonendocrine disease –collagen disease –allergic disease –bronchial asthma –skin disease

14. Mineralocorticoids Aldosterone, Fludrocortisone, Deoxycortone Effects : ญ Na + reabsorption ญ K + excretion

15. Aldosterone Synthesized : zona glomerulosa Reduction in blood volume Aldosterone secretion Several influences Metabolism : similar cortisol

16. Fludrocortisone Potent steroid : glucocorticoid & mineralocorticoid activity

17. Adverse Reactions Na + & H 2 O retention Hypokalemia Hypertension Muscle weakness

18. Clinical Uses Adrenal insufficiency (Addison’s disease or following adrenalectomy)

19. Antagonists of Adrenocortical Agents Glucocorticoid antagonists –Mitotane : adrenal carcinoma –Ketoconazole : Cushing’s disease due to several causes –Mifepristone (RU 486)

20. Antagonists of Adrenocortical Agents Mineralocorticoid antagonists –Spironolactone : 1 o aldosteronism