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Adrenocorticosteroids พญ. มาลียา มโนรถ. Adrenocorticosteroids Emotional stress Hypothalamus CRF Anterior pituitary gland ACTH Adrenal cortex Adrenal steroids.

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Presentation on theme: "Adrenocorticosteroids พญ. มาลียา มโนรถ. Adrenocorticosteroids Emotional stress Hypothalamus CRF Anterior pituitary gland ACTH Adrenal cortex Adrenal steroids."— Presentation transcript:

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 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< Betamethasone< Dexamethasone<

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


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