adrenocorticosteroids & adrenocortical antagonists
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Adrenocorticosteroids &
Adrenocortical antagonists
By
M.D. , Ph.D.Shahid Beheshti University of Medical Science
Adrenocorticosteroids Introduction Classification Mechanism of Action Glucocorticoids (Adverse) Effects Clinical Application Special Issues Contraindications Glucocorticoid Antagonists Drug Pictures
Introduction
Having important effects on intermediary metabolism and immune function (glucocorticoid).
Having principally salt-retaining activity (Mineralocorticoid).
Having androgenic or estrogenic activity.
Cortisol secretion follows a circadian rhythm that peak in the early morning & after meals
Cortisol
Aldosterone
Dehydroepiandrosterone sulfate (DHEAS)
Classification
Short- to medium-acting glucocorticoids
Intermediate-acting glucocorticoids
Long-acting glucocorticoids
Mineralocorticoids
Hydrocortisone (cortisol)Cortisone Prednisone Prednisolone Methylprednisolone
Triamcinolone
Betamethasone DexamethasoneFludrocortisone
Some commonly used natural and synthetic corticosteroids for general use.
Activity
Agent Anti-Inflammatory Topical Salt-
RetainingOral Dose
(mg)
Short- to medium-acting glucocorticoids
Hydrocortisone (cortisol) 1 1 1 20
Cortisone 0.8 0 0.8 25 Prednisone 4 0 0.3 5 Prednisolone 5 4 0.3 5 Methylprednisolone 5 5 0 4 Meprednisone2 5 0 4Intermediate-acting glucocorticoids
Triamcinolone 5 53 0 4
Paramethasone2 10 0 2 Fluprednisolone2 15 7 0 1.5Long-acting glucocorticoids
Betamethasone 25-40 10 0 0.6
Dexamethasone 30 10 0 0.75
Mineralocorticoids Fludrocortisone 10 0 250 2
Glucocorticoids (Adverse) Effects Permissive effects:
The response of vascular and bronchial smooth muscle to catecholamines is diminished in the absence of cortisol.
The lipolytic response of fat cells to catecholamines is attenuated in the absence of glucocorticoids.
Metabolic effects Stimulate gluconeogenesis and glycogen synthesis in
the fasting state. Gluconeogenesis, muscle catabolism and lipolysis
contribute to an adequate glucose supply to the brain.
Glucocorticoids (Adverse) Effects cont,d
Anti-inflammatory & immunosuppressive effects: Decrease in lymphocytes, monocytes, eosinophils &
basophils. Inhibit the functions of macrophages. Reduce prostaglandin & leukotriene synthesis. Reduce expression of cyclooxygenase II. Cause vasoconstriction. Decrease capillary permeability. Inhibit complement effects. Reduce antibody production (large doses).
Glucocorticoids (Adverse) Effects cont,d
Catabolic effects: Decreased muscle mass Weakness Thinning of the skin. Osteoporosis. Reduce growth in children.
Glucocorticoids (Adverse) Effects cont,d
Other effects: Insomnia, euphoria, psychosis & depression. Increased intracranial pressure (pseudotumor
cerebri). Peptic ulcer, by suppressing the local immune
response against Helicobacter pylori. Increase in number of platelets & red blood cells.
Glucocorticoids (Adverse) Effects cont,d
Other effects Cont,d:
Antagonize the effect of vit. D on calcium absorption. Bacterial and mycotic infections, may be masked. Increased intraocular pressure (glaucoma). Severe proximal myopathy. Aseptic necrosis of the hip. Cataract.
Clinical Application of Glucocorticoids
Adrenocortical insufficiency. Congenital Adrenal Hyperplasia. Adrenocortical hyperfunction. For diagnostic purposes.
Almost any kind of inflammatory disease. Stimulation of lung maturation in the fetus.
Dexamethasone suppression test
Dexamethasone Suppression Test
Is used for the diagnosis of cushing's syndrome. Dexamethasone, is given at 11 pm:
Morning cortisol less than 3 mcg/dl => normal individual
Greater than 5 mcg/dl => cushing's syndrome The results are not reliable in the presence of
depression, anxiety, concurrent illness, and other stressful conditions.
Dexamethasone Suppression Test Cont,d
Large doses of dexamethasone helps to distinguish different types of Cushing's syndrome
High dose dexamethasone is given and the urine is assayed for cortisol or its metabolites (Liddle's test).
50% suppression in hormone level => Cushing's disease
No suppression in hormone level: ACTH is low => cortisol-producing adrenal tumor ACTH is high => ectopic ACTH-producing tumor.
Adrenocortical insufficiency
Chronic (addison's disease): Glucocorticoids that are long-acting and devoid of
salt-retaining activity should NOT be administered to these patients.
Acute: Treatment must be instituted immediately. Large amounts of parenteral hydrocortisone.
Congenital Adrenal Hyperplasia
Reduction in cortisol and increase in ACTH (hyperplastic gland).
The most common cause is 21β-hydroxylase deficiency.
Dexamethasone administration to the mother protectes fetuses at risk from genital abnormalities.
Negative feedback on ACTH
Congenital Adrenal Hyperplasia Cont,d
Defect in 11β-hydroxylase.
Hypertension with or without hypokalemic alkalosis.
Defect in 17 α-hydroxylase.
Hypogonadism
Hypertension and hypokalemia.
The affected newborn will be in acute adrenal crisis.
Treatment consists of correction of electrolytes and intravenous hydrocortisone in stress doses.
Adrenocortical hyperfunction Cushing's Syndrome:
The most common cause is an ACTH-secreting pituitary adenoma (Cushing's disease).
May also be due to tumors or nodular hyperplasia of the adrenal gland or ectopic production of ACTH.
Treatment is surgery followed by large doses of hydrocortisone.
Aldosteronism: Is due to adrenal adenoma, hyperplastic gland or
malignant tumor. Treatment (and diagnosis) is by spironolactone.
Special Issues In inflammation & allergy, use less frequent – higher
doses. In less than 2 weeks treatment, adverse effects are
unusual. Daily doses of 100 mg of hydrocortisone for longer than
2 weeks suppress adrenal gland. Chronic therapy with these drugs should be undertaken
with great care. If possible, the drug should be given as a single morning
dose.
Glucocorticoid therapy can reactivate dormant disease
Special Issues Cont,d
When large doses are required for prolonged periods, try alternate-day administration after control is achieved.
In prolonged treatment, at the time of severe stress the dose should be raised up to ten times for 72 hr.
In prolonged therapy, obtain a chest x-rays and a tuberculin test.
Therapy should not be decreased or stopped abruptly.
Patients treated with corticosteroids should be on high protein and potassium-enriched diets. It takes 2-12 months for the HPA axis to function
acceptably, and cortisol levels may not return to normal for another 6-9 months
Contraindications
Peptic ulcer Heart disease Hypertension Varicella Tuberculosis
Psychoses Diabetes Osteoporosis Glaucoma
Glucocorticoid Antagonists
Metyrapone: Inhibits 11-hydroxylation, interfering with cortisol and
corticosterone synthesis. It is the only adrenal-inhibiting medication that can be
administered to pregnant women with Cushing's syndrome. The adverse effects are salt - water retention and hirsutism.
Ketoconazole: Is a potent inhibitor of adrenal and gonadal steroid synthesis. These effects are seen only at high doses. Has been used for the treatment of Cushing's syndrome.
Glucocorticoid Antagonists Cont,d
Mifepristone (RU 486) Has strong antiprogestin activity. High doses exert antiglucocorticoid activity by
blocking the glucocorticoid receptor. Only for inoperable patients with ectopic ACTH
secretion or adrenal carcinoma who have failed to respond to other therapies.
Glucocorticoid Antagonists Cont,d
Aminoglutethimide: Blocks the conversion of cholesterol to pregnenolone and
reduces the synthesis of all hormonal steroids.
It is used with dexamethasone or hydrocortisone to reduce estrogen production in breast carcinoma.
Spironolactone: Reverses manifestations of primary aldosteronism
It is also an androgen antagonist so is used in treatment of hirsutism.
This effect is seen in 2 months and maximizes in 6 months.
Estradiol gel
Hydrocortisone
tetracosactide
triamcinolone oral paste
SummaryIn English
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