A.

Glucocoticoids
- Cortisol is the principal human G.C - Its production is diurnal, with a peak early in the morning followed by a decline & then a secondary, smaller peak in the late afternoon. - Factor such as stress & levels of the circulating steroid influence secretion

1- Promote normal intermediary metabolism

All G.Cs

- G.C favor gluconeogenesis: by increasing A.A up take - Stimulate protein catabolism [ except in the liver ] & lipolysis providing the building up energy that are needed for glucose syn. [ G.C insufficiency may result in hypoglycemia ]

2- Increase resistance to stress

By raising plasma glucose levels & provide the body with energy it requires to combat stress caused for e.g: by trauma , fright, infection & bleeding

3- Alter blood cell levels in plasma

-Cause a decrease in eosinphils, basophils, monocytes & lymphocytes by redistribution them from the circulation to lymphoid tissue. -Increase blood level of Hb, erythrocytes, platelets & polymorphonuclear leukocyte -The decrease in circulating Lymphocyte & Macrophages compromises the bodys ability to fight infections, but this property is important in the treatment of leukemia

4- Anti-inflammatory action
-G.C dramatically reduce the inflammatory response & to suppress immunity - The lowering & inhibition of peripheral Lymphocyte & Macrophages is known to play a role - Also involved of indirect inhibition of phospholipase A2 - Cyclooxygenase-II syn. in inflammatory cells is further reduced, lowering the availability of PGs - Decreased in histamine released & capillary permeability

5- Affect other component of endocrine system

- Feed back inhibition of corticotropin production by elevated G.C

causes inhibition of further G.C syn. - In contrast , growth hormone production is increased

6- Effect of other systems -Adequate cortisol level are essential for normal glomerular filtration - High dose of G.C stimulate gastric acid & pepsin production & may exacerbate ulcer - Chronic G.C therapy can cause severe bone loss

Mineralocorticoids
-Help to control the bodys water volume & conc. of electrolyte, especially sodium & potassium -Aldosterone acts on kidney tubules & collecting ducts, causing a reabsorption of Na, bicarbonate & water -Conversely, Aldosterone decreases reabsorption of K, with H+ & lost in the urine -Enhancement of Na reabsorption by Aldosterone also occurs in GI mucosa & in sweat & salivary glands

-Elevated Aldosterone: alkalosis, hypokalemia, retention of Na & H2O which in turn increase the b.pr
-Interaction of Aldosterone with the receptors occur in the same manner to that of G.C receptors

Clinical uses of adrenal corticosteroids

1- Replacement therapy for primary adrenocortical insufficiency [ Addison disease ] -Adrenal cortex dysfunction -Treatment with Hydrocortisone which is identical to natural cortisol 2- Replacement therapy for secondary and tertiary adrenocortical insufficiency -These deficiencies caused by a defect either in CRH( corticotropinreleasing hormone) production by the hypothalamus or in corticotropin production by the pituitary gland. -Hydrocortisone is also used

3- Diagnosis of Cushing syndrome -Dexamethasone is used

4- Replacement therapy for congenital adrenal hyperplasia

5- Treatment of allergies -G.C effective in treatment of the symptoms of bronchial asthma, allergic rhinitis & drug, serum & transfusion allergic reaction

6- Acceleration of lung maturation Respiratory distress syndrome is a problem in premature infection Fetal cortisol is a regulator of lung maturation 7- Relief of inflammatory symptoms G.C dramatically reduce the manifestation of inflammations [ e.g: rheumatoid & osteoarthritic inflammation, & inflammatory condition of the skin ] , including the redness, swelling, heat & tenderness that commonly present at inflammatory site.

The effect of G.C on the inflammatory process is the result of :

A- Redistribution of leukocytes to other body compartments their function is also compromised B- Increase the conc. of lymphocyte [ T & B ], basophils, eosinophils & monocytes C- Decrease in the conc. of neutrophils D- Inhibition the ability of leukocytes & macrophages to respond to mitogens & antigens. E- The decrease production of PG & leukotrienes is believed to be central to the anti- inflammatory action F- Also decrease or reduce the amount of histamine released.

In determining the dosage of adrenocortical steroids , many factors need to be considered :1- G.C versus Mineralocorticoids activity 2- Duration of action 3- Type of preparation 4- Time of drug that the steroid is administered

Withdrawal effect of G.C

-Withdrawal from these drugs can be a serious problem bec. If patient has hypothalamic pituitary adrenal [HPA ] suppression as a result of long-term G.C administration -Abrupt removal of the corticosteriods causes an acute adrenal insufficiency syndrome that can be lethal - Withdrawal might cause an exacerbation of the disease - So the dose of corticosteriods must be tapered according to the individual - the patient must be monitored carefully

Adverse effects

1- Metyrapone -Is used for taste of adrenal function & can be used for the treatment of pregnant women in cushing syndrome. 2- Aminoglutathimide -Has been used therapeutically in the treatment of breast cancer or eliminate androgen & estrogen production -Also it may be useful in the treatment of malignancies of the adrenal cortex to reduce the secretion of steriods. 3- Ketoconazole -Antifungal agent that strongly inhibits all gonadal & adrenal steriod hormone syn. -Used in the treatment of patient with Cushing syndrome 4- Spironolactone - Antihypertensive drug that competes for the mineralocorticoid receptor & thus inhibit Na reabsorption in the kidney -Antagonize aldosterone & testosterone syn. -It effective against hyperaldosteronism -Useful in the treatment of hirsutism in women , probably due to interference at the androgen receptor of the hair follicle.

Inhibitors of Adrenocorticoid Biosynthesis