Corticosteroids & Antagonists

Question 1

Immunosuppressive effects of glucorticoids.

Answer 1

• Inhibit lymphocyte dependent mediated immunologic functions.
• Are actively lymphotoxic thus important in treatment of hematologic cancers.
• Does not interfere with normal acquired immunity but delay rejection actions in patients with organ transplant.

Question 2

Mechanism of action of Glucocorticoids.

Answer 2

1. Corticosteroids enter the cell and bind to cytosolic receptors that transport the steroid into the nucleus.
2. The steroid-receptor complex alters gene expression by binding to glucocorticoid response elements (GREs) or mineralocorticoid-specific elements.
3. Tissue specific responses to steroids are made possible by the presence in each tissue of different protein regulators that control the interaction between the hormone-receptor complex and particular DNA response elements.

Question 3

The major natural glucocorticoid.

Answer 3

Cortisol.

Question 4

Adrenocorticotropin (ACTH)

Answer 4

Regulates release of Cortisol.

Question 5

Corticosteroid binding Globulin. (CBG)

Answer 5

In plasma, cortisol is 95% bound to CBG

Question 6

Synthetic Glucocorticoids.

Answer 6

1. Prednisone and its active metabolite.
2. Prednisolone
3. Dexamethasone
4. Triamcinolone

Question 7

Synthetic glucocorticoids compared to cortisol.

Answer 7

1. Longer half-life
2. Longer duration of action.
3. Reduced salt retaining effect.
4. Better penetration of lipid barriers for topical activity.

Question 8

Beclomethasone and Budesonide.

Answer 8

Special glucocorticoids that readily penetrate the airway mucosa but have very short half-lives after they enter the blood, so that systemic effects and toxicity are greatly reduced.

Question 9

Betamethasone.

Answer 9

A glucocorticoid with a low degree of protein binding, is given to pregnant women in premature labor to hasten maturation of fetal lungs.

Question 10

Adrenal disorders and glucocorticoids.

Answer 10

1. Chronic adrenal cortical insufficiency (Addison’s disease)
2. Congenital adrenal hyperplasia.
3. Acute adrenal insufficiency.

Question 11

Noradrenal disorders.

Answer 11

1. Asthma
2. Organ transplant rejection.
3. Collagen diseases.
4. Rheumatic disorders.

Question 12

Major natural mineralocorticoid.

Answer 12

Aldosterone.

Question 13

Angiotensin II

Answer 13

Controls aldosterone secretion.

Question 14

Regulation of Aldosterone

Answer 14

1. ACTH

2. RAS

Question 15

Other mineralocorticoids.

Answer 15

1. Deoxycorticosterone - natural precursor of aldosterone.

2. Fludrocortisone - for replacement therapy after adrenalectomy.

Question 16

Receptor Corticosteroid Antagonists.

Answer 16

1. Spironolactone and Eplerenone.
2. Mifepristone (RU-486)
   - To treat Cushing’s syndrome.
   - A competitive inhibitor of glucocorticoid receptors.

Question 17

Corticosteroid synthesis inhibitors.

Answer 17

1. Ketoconazole
   - An antifungal.
   - Inhibits cytochrome P450 enzymes necessary for synthesis of all steroids.
   - For adrenal carcinoma, hirutism, breast and prostate cancer.
2. Aminoglutethimide
   - Blocks conversion of cholestrol to prognenolone.
   - Inhibits synthesis of hormonally active steroids.
3. Metyrapone
   - Blocks normal synthesis of cortisol but not of cortisol precursors,
   - Used in diagnostic tests of adrenal function.