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)