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

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




Mechanism of action
Mechanism of Action (HYDROCORTISONE)


The glucocorticoid receptor polypeptide
The glucocorticoid receptor (HYDROCORTISONE) polypeptide




Metabolic effect
Metabolic effect general

  • Gluconeogensis

  • Muscle protein catablism

  • Lipolysis

  • Lipogenesis

  • Increase in insulin release

  • Decrease in glucose uptake in muscle


Catabolic effect
Catabolic effect general

  • Muscle protein catabolism

  • Wasting of

    • Lymphoid

    • connective tissue

    • Fat

    • Skin

  • Steoporesis

  • Growth inhibition in children


Immunosuppressive effects
Immunosuppressive effects general

  • Inhibit cell-mediated immunologic functions

  • Lymphotoxic

  • Important in the therapy of hematologic cancers


Anti inflammatory effects
Anti-inflammatory effects general

  • 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 general

  • 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 general

  • 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 general

  • 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 general

  • 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 general

  • SPECIAL PRECAUTIONS

    • monitored carefully for the development of :

      • hyperglycemia, glycosuria, sodium retention with edema

      • hypertension, hypokalemia, peptic ulcer, osteoporosis, and hidden infections


Contraindications
CONTRAINDICATIONS general

  • 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 general

  • SYNTHESIS INHIBITORS

    • Metyrapone

    • Aminoglutethimide

    • Ketoconazole

    • Trilostane

  • GLUCOCORTICOID ANTAGONISTS

    • Mifepristone (RU 486)


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