1. Steroidal Hormones (Adrenocorticosteroids, Adrenocorticoids, Corticosteroids, Corticoids)
Secretion:
Adrenal cortex of the adrenal gland.
Regulation:
Stimulation: ACTH.
Inhibition: Feed back Mechanism.

2. Classification of corticosteroids
They are all C21 hormones.

3. Numbering System of Steroidal ring:

5. Physiological Functions and Pharmacological Effects:
Carbohydrates and Proteins Metabolism:
Stimulate glucose formation in the brain.
Decrease peripheral utilization of glucose.
Promote storage of glucose in the liver.
Promote gluconeogenesis.
Lipids Metabolism:
Redistribution of body fat (Buffalo hump, Moon face).
Enhance lipolyses of Triglycerides.
Electrolyte and Water balance:
Enhance reabsorption of sodium and water into plasma.
Increase urinary excretion of potassium.

6. Anti-inflammatory effects:
Blood Picture:
Increase hemoglobin and Red blood cells.
Decrease white blood cells.
Anti-inflammatory effects:
Suppress inflammations regardless to their cause.
Immunosuppressive Effects:
Decrease immunity as a result of decrease the WBC’s.
Cell Growth:
Retardation of cell division and cell growth.

7. Disease States: Addison’s disease:
Rare syndrome 1/100,000 due to Hypoadrenalism.
Causes:
Atrophy of adrenal gland.
Tuberculoses.
Low level of ACTH.
Symptoms:
Weakness, fatigue, apathy, depression and irritability.
Anemia and low blood pressure.
Loss of sodium and dehydration.
Hypersensitivity to Insulin.
Hyper pigmentation.
Nausea and vomiting.

8. Cushing’s disease: Conn’s syndrom:
Rare syndrome 2- 5/Million due to Hyperadrenalism.
Causes:
Tumor of the Adrenal Cortex.
Tumor of the Pituitary gland.
Symptoms:
Alteration of fat distribution.
Hypertension.
Osteoporosis.
Growth retardation.
Decrease Immunity.
Conn’s syndrom:
Inability of adrenal cortex to carry out 17a-hydroxylation of pregnenolone. That leads to low level of Cortisol and high level of Aldosterone.
Alkalosis.
Polyuria.
Edema.

9. Pharmacokinetics: Absorption: Plasma Protein binding:
Well absorbed from all sites of administration.
Plasma Protein binding:
90% to albumin or globulin.
Half life (t1/2):
hr.
Metabolism and Excretion:
Excreted in urine after glycosylation with glucuronic acid.

11. Adrenocorticoid Drugs
Systemic Corticosteroids:
They can be administered by IV, IM injections, oral, topical or by inhalation.
They can be short, intermediate or long-acting. Unlike natural corticoids they do not undergo first pass metabolism.
Cortisone and Cortisone acetate:
Can be given orally or by IM injection.
Acetate has longer duration of action.
Drug of choice in replacement therapy.

12. Prednisone and Prednisolone:
Fludrocortison:
9a-fluorocortisone.
10 times more active than cortisone as antiinflammatory.
times more active as mineralocorticoids.
Prednisone and Prednisolone:
They are Δ1 corticoids.
3, 4 times more active than cortisone and hydrocortisone.
Prepared by microbial dehydrogenation (Corynebacterium simplex) or chemically using SeO2.

13. Triamcinolone: Dexamethasone: Betamethasone:
9a-fluoro, 16a-hydroxyprednisolone.
Activity equal to prednidolone but with less mineralocorticoid activity.
Dexamethasone:
9a-fluoro, 16a-methylprednisolone.
5- 7 times more active than prednidolone.
Betamethasone:
9a-fluoro, 16b-methylprednisolone.
Slightly more active than Dexamethasone.

14. Topical Corticosteroid:
Beclomethasone:
9a-fluoro, 16b-methylprednisolone.
9a-chloro analog of Betamethasone.
Topical activity 500 times more than Betamethasone.

15. Inhaled Corticosteroids:
Beclomethasone 17, 21-dipropionate (BDP):
Prodrug metabolized to more active 17-BMP.
17-BMP is 30 times more active than BDP.
Topical activity 500 times more than Betamethasone.
Triamcinolone Acetonide:

16. Clinical uses: Hypoadrenalism. Rumatic diseases. Renal diseases.
Collagen diseases.
Ocular diseases.
Skin diseases.
GIT inflammation.
Liver diseases.

17. Diagnostic uses: Cause of Hyperadrenalism:
Non specific due to obesity or stress.
Cushing’s syndrome.
2 mg Dexamethasone every 6 hr for 8 doses to diagnose the cause.

18. Side effects: Due to Prolonged use: Withdrawal Symptoms:
Fluid and electrolyte disturbances, edema and hypertension.
Hyperglycemia and glucosuria.
Peptic ulcer.
Osteoporoses
Myopathy
Growth arrest
Increase susceptibility to infections.
Withdrawal Symptoms:
Rapid withdrawal after prolonged use leads to sever hypoadrenalism.