1. Adrenocortical hormones

2. Classification of Adrenocortical Hormones
Glucocorticoids
Mineralocorticoids
Sex hormones

3. 1. Glucocorticoid
Short acting: hydrocortisone, Prednisone (8-12 hours)
Intermediate-acting: triamcinolone (12-36 hours)
Long acting: dexamethasone (48 hours)

4. Pharmacokinetics:
Well absorbed after oral administration.
75% of corticosteroids are bound to plasma globulins (CBG). CBG is increased by estrogen and decreased in liver cirrhosis.
Metabolism is by the liver and excretion is by the kidney.
Mechanism of action:
Corticosteroids transported to the nucleus, where it interacts with many DNA receptors (genes) and affect their function.

5. Pharmacological effects:
On metabolism:
Carbohydrate metabolism: hyperglycemia (↓ peripheral glucose utilization).
Protein metabolism: Catabolic effect → ↓ muscle mass and thin limbs.
Fat metabolism: ↑ lipolysis with redistribution of fat.
Na+ & water retention and hypokalemia.

6. Anti-inflammatory and anti-immunological effects:
Inhibit antigen-antibody reaction.
Inhibit lymphocyte and macrophage activity and function.
Stabilize lysosomal membrane.
↓ release of inflammatory mediators and cytokine production by inflammatory cells.
Inhibit phospholipase A2 enzyme so reduce synthesis of PGs & LTs.
↓ capillary permeability.

7. CVS: Hypertension due to Na+ & water retention.
Hematological effects:
↑ RBCs and ↓ lymphocytes and eosinophils.
↑ coagulation factors and blood cholesterol.
On growth:
Growth retardation, which is not prevented by growth hormone.
On bone:
↓ bone matrix and ↑ Ca2+ excretion (osteoporosis).
Inhibit hypothalamo-pituitary-adrenal axis.

8. Doses:
Short-term therapy: duration of therapy is < 2 weeks.
Long term therapy: duration of therapy is > 3 weeks.
Alternate day therapy: double the dose and give it every other day.

9. Therapeutic uses:
As replacement therapy in adrenocortical insufficiency:
Acute adrencortical insufficiency (acute addisonian crisis
Chronic adrenocortical insufficiency (Addison’s disease).
Adrenocortical hyperplasia due to elevated ACTH:
Congenital adrenal hyperplasia:
Cushing syndrome: due to pituitary adenoma, adrenal tumors.

10. Stimulation of lung maturation in the fetus
Anti-inflammatory: e.g. vasculitis, rheumatic fever, arthritis, bronchial asthma, etc.
Allergic diseases: e.g. anaphylactic shock, urticaria and bronchial asthma.
Autoimmune disease: e.g. SLE
Shock and hypotension
Organ transplantation: as immunosuppressive to prevent graft rejection.
Cerebral edema: dexamethasone is used after brain surgery to minimize edema.
Acute hypercalcemia: to enhance Ca2+ excretion.

11. Side effects:
Acute adrenal insufficiency (acute addisonian crisis):
It occurs after sudden withdrawal of corticosteroids after prolonged administration.
Prevention: Gradual withdrawal of corticosteroids.
Iatrogenic Cushing syndrome:
Occurs if high doses used or it is used for > 2 -3 weeks. It is characterized by moon face, buffalo hump, weak muscles, osteoporosis, hypertension, DM, edema, etc.

13. Immune suppression leading to:
Flaring of infections (especially viral and TB).
Decrease wound healing
Peptic ulcer
Due to prolonged PGs suppression.
Rise of IOP (Glaucoma).
Hyperglycemia.
Hypercoagulability leading to thromboembolism
Osteoporosis.
Retardation of growth in children.
Pregnancy: congenital cleft palate.

14. Local side effects:
Skin atrophy & hypopigmentation on prolonged use.
Repeated administration in joints may produce joint destruction & infection

15. Contraindications:
Presence of infections: especially viral infection and TB: because corticosteroids can inhibit immune functions.
N.B. Uses of corticosteroids in presence of T.B:
TB meningitis: to prevent adhesions.
TB of the suprarenal gland: to correct hypofunction.
Miliary TB: to ↓ TB toxemia.

16. Peptic ulcer: they ↓ synthesis of PGE2 and I2 that protect the stomach.
Hypertension & heart failure: they cause salt and water retention.
DM (except fluorinated corticosteroids e.g. dexamethasone and betamethasone because they have anti-inflammatory with less hyperglycemic effects).
Mental disorders e.g. psychosis or depression.
In early pregnancy: may cause cleft palate.

17. Drug interactions:
With NSAIDs: ↑ incidence of peptic ulcer and decreases its healing
With insulin: It has anti-insulin effect (hyperglycemia)
With anticoagulant drugs: it decreases their effect.
With loop diuretics: it aggravate hypokalemia.

18. Mineralocorticoids Natural mineralocorticoids: Aldosterone
It binds to specific intracellular receptors in the distal convoluting tubules to inhibit Na+ excretion and stimulates K+ and H+ excretion.
2. Synthetic mineralocorticoids
Deoxycorticosterone acetate(DOCA)
It has mainly mineralocorticoid effect.
Fludrocortisone
It has both glucocorticoid and mineralocorticoid effect.

19. Adverse effects
Hypernatremia
Hypervolemia
Hypokalemic alkalosis (weakness, paralytic ileus and tetany)
Hypertension
Therapeutic uses
Acute adrenal insufficiency
Chronic adrenal insufficiency (Addison's disease)

20. Hyperaldosteronism Treatment of hyperaldosteronism:
Primary hyperaldosteronism: by surgical removal of tumor.
Secondary hyperaldosteronism: Aldosterone antagonists: spironolactone.

21. Adrenocortical hormone antagonists
A. Glucocorticoid inhibitors:
Aminoglutethimide:
Inhibit steroid hormone synthesis .
Used in adrenocortical malignancies and cancer breast. In postmenopausal or Ovariectomized women with metastatic breast cancer (to eliminate adrenal estrogen production
Metyrapone:
It inhibits enzyme necessary for synthesis of glucocorticoids.
Used to measure the capacity of the anterior pituitary to secrete ACTH.

22. Ketoconazole:
It is antifungal drug with slight inhibition of mineralocorticoids synthesis.
Used in Cushing’s syndrome
Mifepristone
Blockade cytoplasmic glucocorticoid receptor
Inoperable patients with ectopic ACTH secretions or adrenal carcinoma (it is also an antiprogestin)

23. B. Aldosterone receptors inhibitors:
Spironolacone
Blockade of cytoplasmic mineralocorticoid receptor
(used in hyperaldosteronism)

24. Good luck