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Adrenocorticosteroids & Adrenocortical Antagonists
ByS. Bohlooli, PhD
School of Medicine, Ardabil University of Medical Sciences
ADRENOCORTICOSTEROIDS
THE NATURALLY OCCURRING GLUCOCORTICOIDS
SYNTHETIC CORTICOSTEROIDS
THE NATURALLY OCCURRING GLUCOCORTICOIDS; CORTISOL (HYDROCORTISONE)
Pharmacodynamics MECHANISM OF ACTION PHYSIOLOGIC EFFECTS METABOLIC EFFECTS CATABOLIC AND ANTIANABOLIC EFFECTS ANTI-INFLAMMATORY AND
IMMUNOSUPPRESSIVE EFFECTS OTHER EFFECTS
Adrenocortical hormone biosynthesis
Chemical structures of several glucocorticoids
Mechanism of Action
The glucocorticoid receptor polypeptide
Activity1
AgentAnti-Inflammatory
TopicalSalt-
Retaining
Equivalent Oral Dose (mg)
Forms Available
Short- to medium-acting glucocorticoids
Hydrocortisone
(cortisol)1 1 1 20
Oral, injectable, topical
Cortisone 0.8 0 0.8 25 Oral
Prednisone 4 0 0.3 5 Oral
Prednisolone 5 4 0.3 5 Oral, injectable
Methylprednisolone 5 5 0 4 Oral, injectable
Meprednisone2 5 0 4 Oral, injectable
Some commonly used natural and synthetic corticosteroids for general
Intermediate-acting glucocorticoids
Triamcinolone 5 53 0 4Oral, injectable,
topical
Paramethasone2 10 0 2 Oral, injectable
Fluprednisolone2 15 7 0 1.5 Oral
Long-acting glucocorticoids
Betamethasone 25-40 10 0 0.6Oral, injectable,
topical
Dexamethasone 30 10 0 0.75Oral, injectable,
topical
Some commonly used natural and synthetic corticosteroids for general
Activity1
AgentAnti-
InflammatoryTopical
Salt-Retaining
Equivalent Oral Dose
(mg)
Forms Available
Metabolic effect
Gluconeogensis Muscle protein catablism Lipolysis Lipogenesis Increase in insulin release Decrease in glucose uptake in
muscle
Catabolic effect Muscle protein catabolism Wasting of
Lymphoid connective tissue Fat Skin
Steoporesis Growth inhibition in children
Immunosuppressive effects
Inhibit cell-mediated immunologic functions
Lymphotoxic Important in the therapy of
hematologic cancers
Anti-inflammatory effects Dramatic effect of distribution and
function of leukocyte Increase neutrophils Decrease lymphoctes, eosinophils,
basophils, monocytes Inhibition of leukocyte migration
Inhibition of PLA2 Decreased production of COX2 Decrease in IL2, IL3, and PAF
Other effects
Need for normal excretion of water load
Effect of CNS: Low level: depression High level: behavioral changes
Large doses: stimulation of gastric acid secretion and peptic ulcer
Clinical Pharmacology DIAGNOSIS AND TREATMENT OF DISTURBED
ADRENAL FUNCTION Adrenocortical insufficiency
Chronic (Addison's disease) Acute
Adrenocortical hypo- and hyperfunction Congenital adrenal hyperplasia Cushing's syndrome Aldosteronism
Use of glucocorticoids for diagnostic purposes CORTICOSTEROIDS AND STIMULATION OF
LUNG MATURATION IN THE FETUS
CORTICOSTEROIDS AND NONADRENAL DISORDERS
CORTICOSTEROIDS AND NONADRENAL DISORDERS Many disorders respond to coticosteroids Inflammatory or immunologic diseases:
Asthma, organ transplant rejection, collagen disease
Hematopoietic cancers Neurolgic disorders Chemotherapy induced vomiting Hypercalcemia Mountain sickness Hasten maturation of the fetal lungs
Toxicity METABOLIC EFFECTS
Growth inhibition, diabetes, muscle wasting, salt retention, psychosis,
OTHER COMPLICATIONS Peptic ulcer, masking of bacterial and fungal disease
clinical finding acute psychosis ,growth retardation
ADRENAL SUPPRESSION
Contraindications & Cautions
SPECIAL PRECAUTIONS monitored carefully for the
development of : hyperglycemia, glycosuria, sodium
retention with edema hypertension, hypokalemia, peptic
ulcer, osteoporosis, and hidden infections
CONTRAINDICATIONS
Great caution in patients with: Peptic ulcer Heart disease or hypertension with
heart failure Psychoses Diabetes Osteoporosis Glaucoma
ANTAGONISTS OF ADRENOCORTICAL AGENTS
SYNTHESIS INHIBITORS Metyrapone Aminoglutethimide Ketoconazole Trilostane
GLUCOCORTICOID ANTAGONISTS Mifepristone (RU 486)