Adrenocorticosteroids adrenocortical antagonists
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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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Adrenocorticosteroids adrenocortical antagonists

Adrenocorticosteroids & Adrenocortical Antagonists

By

S. Bohlooli, PhD

School of Medicine, Ardabil University of Medical Sciences


Adrenocorticosteroids

ADRENOCORTICOSTEROIDS

  • THE NATURALLY OCCURRING GLUCOCORTICOIDS

  • SYNTHETIC CORTICOSTEROIDS


The naturally occurring glucocorticoids cortisol hydrocortisone

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

Adrenocortical hormone biosynthesis


Chemical structures of several glucocorticoids

Chemical structures of several glucocorticoids


Mechanism of action

Mechanism of Action


The glucocorticoid receptor polypeptide

The glucocorticoid receptor polypeptide


Some commonly used natural and synthetic corticosteroids for general

Some commonly used natural and synthetic corticosteroids for general


Some commonly used natural and synthetic corticosteroids for general1

Some commonly used natural and synthetic corticosteroids for general


Metabolic effect

Metabolic effect

  • Gluconeogensis

  • Muscle protein catablism

  • Lipolysis

  • Lipogenesis

  • Increase in insulin release

  • Decrease in glucose uptake in muscle


Catabolic effect

Catabolic effect

  • Muscle protein catabolism

  • Wasting of

    • Lymphoid

    • connective tissue

    • Fat

    • Skin

  • Steoporesis

  • Growth inhibition in children


Immunosuppressive effects

Immunosuppressive effects

  • Inhibit cell-mediated immunologic functions

  • Lymphotoxic

  • Important in the therapy of hematologic cancers


Anti inflammatory effects

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

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

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

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

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

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

CONTRAINDICATIONS

  • Great caution in patients with:

    • Peptic ulcer

    • Heart disease or hypertension with heart failure

    • Psychoses

    • Diabetes

    • Osteoporosis

    • Glaucoma


Antagonists of adrenocortical agents

ANTAGONISTS OF ADRENOCORTICAL AGENTS

  • SYNTHESIS INHIBITORS

    • Metyrapone

    • Aminoglutethimide

    • Ketoconazole

    • Trilostane

  • GLUCOCORTICOID ANTAGONISTS

    • Mifepristone (RU 486)


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