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STEROID HORMONES
‐ Adrenal cortex is devided into 3 zones that synthesize various steroid from cholesterol & secrete
them.
‐ Outer zona glomerulosa produce mineral corGcoids ( for eg. : aldosterone ) which are responsible
for regulated primarily by the renin‐angiotensin system.
‐ Middle zona fasciculate synthesis glucocorGcoids ( for eg. : corGsol ) which are concerned with
normal metabolism & resistance to stress.
‐ Inner zona re2cularis secrete adreanal androgens.
SecreGon by the 2 inner zones and some extend, the outer zone is controlled by pituitary ( corGcotrophin
which is released in response to the hypothalamic CRF‐CorGcotropin releasing hormone).
Glucocor2coid serve as feedback inhibitors of corGcotrophin & CRF secreGon.
Mechanism of acGon.
‐ AdrenocorGcoids bind to specific intracellular cytoplasmic receptors in target Gssue.
‐ Receptor ‐hormone complex then translocate into the nucleus where it acts as a transcripGon factor
to turn genes on or off, depending on the Gssue.
‐ The mechanism requires Gme to produce an effect.
‐ There are other glucocorGcoid effects such as their requirement for cathecolamine‐mediated
dilaGon of vascular & bronchial musculature or lipolysis, whose effects are immediate.
‐
GlucocorGcoids ( GCs )
‐ Short acGng ( T ⅟₂ = 12 Hrs ) : hydrocorGsone
‐ Intermediate acGng ( T⅟₂ = 36 Hrs ) : prednizolon
‐ Long acGng ( T⅟₂ = > 36 Hrs ) : triamcinolone, betamethasone
‐ ~they can use as therapeuGc agents in a variety of disorders.
PharmacokineGcs of GCs
(1). Promote normal & immediate metabolism
‐ GCs favor gluconeogenesis by both ↑ amino acid uptake by the liver & kidney , elevaGng acGviGes of
gluconeogenesis enzymes.
‐ GCs sGmulate protein catabolism ( except in the liver )& lipolysis thereby providing the building blocks and
energy needed for glucose synthesis.
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(2). Increasing resistance to stress
‐ by raising plasma glucose levels, GCs provide the body with the energy it requires to combat stress caused
for eg. By trauma, fright, infecGon, bleeding or debilitaGng disease.
(3). After blood cell levels in plasma
‐ GCs cause a ↓ in eosinophils , basophils , monocytes and lymphocytes.
‐ in contrast, they ↑ the blood levels of Hb, RBC & platelets, polymorphonuclear leukocyte ( important for
treatment of leukemia )
(4). An>‐inflamma>on ac>on
‐ the most important therapeuGc property of GCs is their ability to dramaGcally reduce the inflammaGon
response & to suppress immunity.
‐ the exact mechanism is complex & incompletely understood.
‐ however, it is known that the lowering & inhibiGon of peripheral lymphocytes & macrophage play a role.
‐ also involved is the indirect inhibiGon of phospholipase A₂ (due to the steroid mediated elevaGon of
lipocorGn ) ,which blocks the release of arachidonic acid‐ the precursor of the prostaglandin & leukotreines
from membrane‐ bound phospholipid.
(5). Affect other component of endocrine system
‐ feedback inhibiGon of corGcotrophin (ACTH) producGon , ↑GCs cause inhibiGon of further glucocorGcoid
synthesis as well as thyroid sGmulaGng hormone producGon, whereas growth hormone producGon is ↑.
(6). Effects on other systems
‐ there are mostly associated with the adverse effects on the hormones.
‐ high doses of GCs sGmulate gastric acid & pepsin producGon & may exacerbate ulcers.
‐ effects on the CNS that influence mental status have been idenGfied.
‐ chronic glucocorGcoid therapy can cause severe bone loss.
‐ myopathy leads paGents to complain of weakness.
TherapeuGc use of GCs
1. Replacement therapy for primary adrenocor>cal insufficiency (Addison disease)
‐ This disease is caused by adrenal cortex dysfuncGon.
‐ HydrocorGsone is given to correct the deficiency.
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2. Replacement therapy for secondary adrenocor>cal insufficiency
‐ The deficiency are caused by a defect either in CRF producGon by the hypothalamus or
corGcotrophin producGon by pituitary.
‐ HydrocorGsone is given.
3. Diagnosis of Cushing’s syndrome
‐ This syndrome is caused by a hypersecreGon of GCs that is due to either excessive release of
corGcotrophin by the anterior pituitaty gland or to an adrenal tumor.
‐ The Dexamethasone suppression test is used to diagnose the cause of individual case of Cushing’s
syndrome.
‐ This syntheGc glucocorGcoid release by individual with pituitary dependent Cushing’s syndrome but
it does not suppress glucocorGcoid release from adrenal gland.
4. Relief of inflamma>on symptoms
‐ GCs reduce the manifestaGon of inflammaGon. (eg. : rheumatoid & osteoarthriGc inflammaGon,
inflammaGon condiGon of the skin ) including the redness, swelling, heat & tendernedd that are
commonly present in inflammatory site.
5. Treatment of allergies
‐ GCs are useful in the treatment of the symptoms of drug, serum & transfusion allergic reacGon,
bronchial asthma & allergic rhiniGs.
‐ Betanethasone. Triamanolone, Prednizolone are most effecGve.
6. Autoimmune disease
7. Organs transplanta>on
8. Lympha>c leukemia
Adverse effects of GCs
a. Osteoporosis
b. PepGc ulceraGon
c. Glucosuria ( hyperglycemia )
d. ↑ risk of infecGon
e. ↑ appeGte
f. Hypertension
g. Edema
h. Euphoria
i. Psychoses
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Mineralcor>coids
1. DesoxycorGcosteronacetate (DOCA)
2. FludrocorGsone
3. Aldosterone
They have only mineralcorGcoid acGvity :
‐ ↑ renal excreGon of Ca ²⁺ & K⁺.
‐ ↓ renal excreGon of Na⁺ & H₂O.
Adverse effects :
a. Hypokalemia
b. Edema
c. Na⁺ retenGon (without hyperglycemia, osteoporosis, euphoria )
Fludrocor>sone
‐ A potent mineralcorGcoid having some glucocorGcoid acGvity as well, orally acGve used for :
‐ . replacement therapy of Addison disease
‐ . congenital adrenal hyperplasia
‐ . idiopathic postural hypotension
GCs may be :
‐ Orally
‐ InjecGon
‐ InhalaGon
‐ topical
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