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Adrenocorticosteroids & Adrenocortical Antagonists

Adrenocorticosteroids & Adrenocortical Antagonists. By S. Bohlooli, PhD School of Medicine, Ardabil University of Medical Sciences. ADRENOCORTICOSTEROIDS. THE NATURALLY OCCURRING GLUCOCORTICOIDS SYNTHETIC CORTICOSTEROIDS. THE NATURALLY OCCURRING GLUCOCORTICOIDS; CORTISOL (HYDROCORTISONE).

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Adrenocorticosteroids & Adrenocortical Antagonists

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  1. Adrenocorticosteroids & Adrenocortical Antagonists By S. Bohlooli, PhD School of Medicine, Ardabil University of Medical Sciences

  2. ADRENOCORTICOSTEROIDS • THE NATURALLY OCCURRING GLUCOCORTICOIDS • SYNTHETIC CORTICOSTEROIDS

  3. 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

  4. Adrenocortical hormone biosynthesis

  5. Chemical structures of several glucocorticoids

  6. Mechanism of Action

  7. The glucocorticoid receptor polypeptide

  8. Some commonly used natural and synthetic corticosteroids for general

  9. Some commonly used natural and synthetic corticosteroids for general

  10. Metabolic effect • Gluconeogensis • Muscle protein catablism • Lipolysis • Lipogenesis • Increase in insulin release • Decrease in glucose uptake in muscle

  11. Catabolic effect • Muscle protein catabolism • Wasting of • Lymphoid • connective tissue • Fat • Skin • Steoporesis • Growth inhibition in children

  12. Immunosuppressive effects • Inhibit cell-mediated immunologic functions • Lymphotoxic • Important in the therapy of hematologic cancers

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Contraindications & Cautions • SPECIAL PRECAUTIONS • monitored carefully for the development of : • hyperglycemia, glycosuria, sodium retention with edema • hypertension, hypokalemia, peptic ulcer, osteoporosis, and hidden infections

  19. CONTRAINDICATIONS • Great caution in patients with: • Peptic ulcer • Heart disease or hypertension with heart failure • Psychoses • Diabetes • Osteoporosis • Glaucoma

  20. ANTAGONISTS OF ADRENOCORTICAL AGENTS • SYNTHESIS INHIBITORS • Metyrapone • Aminoglutethimide • Ketoconazole • Trilostane • GLUCOCORTICOID ANTAGONISTS • Mifepristone (RU 486)

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