Adrenocortico Steriod Hormones

7/30/2019 Adrenocortico Steriod Hormones

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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

All G.Cs

1- Promote normal intermediary metabolism- 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 stressBy raising plasma glucose levels & provide the body with energy it

requires to combat stress caused for e.g: by trauma , fright,infection & bleeding


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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 & Macrophagescompromises the bodys ability to fight infections, but this propertyis important in the treatment of leukemia

4- Anti-inflammatory action

-G.C dramatically reduce the inflammatory response & to suppressimmunity

-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


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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 & mayexacerbate ulcer

- Chronic G.C therapy can cause severe bone loss


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Mineralocorticoids

-Help to control the bodys water volume & conc. of electrolyte, especially

sodium & potassium

-Aldosterone acts on kidney tubules & collecting ducts, causing areabsorption of Na, bicarbonate & water

-Conversely, Aldosterone decreases reabsorption of K, with H+ & lost inthe urine

-Enhancement of Na reabsorption by Aldosterone also occurs in GI mucosa& in sweat & salivary glands

-Elevated Aldosterone: alkalosis, hypokalemia, retention of Na & H2Owhich in turn increase the b.pr

-Interaction of Aldosterone with the receptors occur in the same mannerto that of G.C receptors


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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 adrenocorticalinsufficiency-These deficiencies caused by a defect either in CRH( corticotropin-releasing hormone) production by the hypothalamus or in corticotropinproduction by the pituitary gland.-Hydrocortisone is also used

3- Diagnosis of Cushing syndrome-Dexamethasone is used

4- Replacement therapy for congenital adrenal hyperplasia


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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 maturationRespiratory distress syndrome is a problem in premature infectionFetal cortisol is a regulator of lung maturation7- Relief of inflammatory symptoms

G.C dramatically reduce the manifestation of inflammations [ e.g:rheumatoid & osteoarthritic inflammation, & inflammatory condition ofthe skin ] , including the redness, swelling, heat & tenderness thatcommonly present at inflammatory site.


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

A- Redistribution of leukocytes to other body compartments theirfunction is also compromisedB- Increase the conc. of lymphocyte [ T & B ], basophils, eosinophils &monocytesC- Decrease in the conc. of neutrophils

D- Inhibition the ability of leukocytes & macrophages to respond tomitogens & antigens.E- The decrease production of PG & leukotrienes is believed to becentral to the anti- inflammatory actionF- Also decrease or reduce the amount of histamine released.


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In determining the dosage of adrenocortical steroids , many factorsneed 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


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Withdrawal effect of G.C

-Withdrawal from these drugs can be a serious problem bec. Ifpatient has hypothalamic pituitary adrenal [HPA ] suppressionas a result of long-term G.C administration-Abrupt removal of the corticosteriods causes an acute adrenalinsufficiency syndrome that can be lethal

-Withdrawal might cause an exacerbation of the disease

- So the dose of corticosteriods must be tapered according to theindividual- the patient must be monitored carefully


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Adverse effects

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Inhibitors of Adrenocorticoid Biosynthesis1- Metyrapone-Is used for taste of adrenal function & can be used for the treatment ofpregnant women in cushing syndrome.

2- Aminoglutathimide-Has been used therapeutically in the treatment of breast cancer or eliminateandrogen & estrogen production-Also it may be useful in the treatment of malignancies of the adrenal cortexto reduce the secretion of steriods.

3- Ketoconazole-Antifungal agent that strongly inhibits all gonadal & adrenal steriod hormonesyn.-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.


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Adrenocortico Steriod Hormones