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)
 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
 Some commonly used natural and
synthetic corticosteroids for general

Activity1
Equival
Anti- Salt- ent
Agent Inflam Topical Retai Oral Forms Available
matory ning Dose
(mg)
Short- to medium-acting glucocorticoids
Hydrocortisone Oral, injectable,
1 1 1 20
(cortisol) 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
Activity1

Equivalent
Anti- Salt- Forms
Agent Topical Oral Dose
Inflammatory Retaining Available
(mg)

Intermediate-acting glucocorticoids
Oral, injectable,
Triamcinolone 5 53 0 4
topical
Paramethasone2 10 0 2 Oral, injectable
Fluprednisolone2 15 7 0 1.5 Oral
Long-acting glucocorticoids
Oral, injectable,
Betamethasone 25-40 10 0 0.6
topical
Oral, injectable,
Dexamethasone 30 10 0 0.75
topical
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)