1 ADRENOCORTICOSTEROIDS Major categories of action: Glucocorticoids: affecting intermediary metabolism & resistance to stress Mineralocorticoids: regulation of salt & water retention Corticosteroids with: androgenic activity estrogenic activity

2 Major glucocorticoid: Cortisol Major mineralocorticoid: Aldosterone Major androgen: Dehydroepiandrosterone (DHEA)

3 Adrenocorticosteriods Short acting Cortisone, Hydrocortisone Intermediate acting Prednisone ( ORAL ),Prednisolone, Methylprednisolone Triamcinolone Long acting Dexamethasone, Betamethasone, Paramethasone

4 Actions Metabolism – increases plasma glucose stress hormone Blood cells : decreases Lymphocytes Monocytes Eosinophils, basophils Immune suppression Anti inflammatory action

5 Others Stimulates gastrin secretion Osteoporosis Myopathy

6 Clinical Uses Diagnosis of adrenal function, i.e Dexamethasone suppression test – Cushings syndrome Treatment of Adrenal function disorders – Addison's disease Inflammatory/immunological disorders (at higher doses) Rheumatoid arthritis, osteoarthritis Allergic reactions Bronchial asthma Acceleration of lung maturation

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11 Special considerations During illness - specially if fever is present Supplemental fludrocortisone (mineralocorticoid) Strenuous exercise with sweating During very hot weather Gastrointestinal upsets

12 Glucocorticoid Toxicity Metabolic Effects iatrogenic Cushing's syndrome moon facies fat redistribution; e.g. truncal obesity acne hirsuitism insomnia, increased appetite weight gain muscle wasting skin thinning, bruising hyperglycemia osteoporosis, Impaired wound healing

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14 Other Effects Peptic ulcer development Myopathy Nausea, dizziness, weight loss Subcapsular cataracts Increased intraocular pressure/glaucoma Psychosis (large dose corticosteroids) Benign intracranial hypertension

15 MINERALOCORTICOIDS Sodium/fluid retention Potassium loss-- hypokalemia Hypochloremic alkalosis Hypertension

16 CI - Adrenocorticosteriods Peptic ulcer disease Heart disease/hypertension with congestive heart failure Psychoses Diabetes Osteoporosis Glaucoma

17 Antagonists of Adrenocortical Agents Metyrapone : selective inhibitor of steroid synthesis Use - Cushing's syndrome Major adverse effects: Salt and water retention Hirsuitism

18 Aminoglutethimide: Blocks cholesterol to pregnenolone conversion Uses ; malignancies of Adrenal cortex + Dexamethasone : Breast Ca Ketoconazole: antifungal imidazole Use - Cushing's disease Mifepristone : anti glucocorticoid + anti progestin

19 Anti Mineralocorticoids Antagonist – Spironolactone Competes for the receptors Inhibits Na reabsorption & prevents K excretion Uses Hyperaldosteronism Hirsutism in women Diuretic