Mechanism: synthetic corticosteroid with anti-inflammatory activities (increased GC activity, decreased MC activity); methylprednisolone (pure GC); DOA: 12-36 hours

Side effects: hyperglycemia, obesity and fat redistribution, osteoporosis, muscle wasting, peptic ulcers, insomnia, behavioral disorders, increased intraocular pressure, glaucoma, and cataracts, bacterial and mycotic infections, adrenal suppression

Mechanism: synthetic corticosteroid with equal GC and MC potency, DOA: 8-12 hours

Side effects: hyperglycemia, obesity and fat redistribution, osteoporosis, muscle wasting, peptic ulcers, insomnia, behavioral disorders, increased intraocular pressure, glaucoma, and cataracts, bacterial and mycotic infections, adrenal suppression

Mechanism: pure, synthetic corticosteroids, DOA: long (36-72hrs)

Treatment: For fetuses at risk of virilization from congenital adrenal hyperplasia, oral dexamethasone;  for babies expected before 34 weeks of gestation, give betamethasone IM for fetal lung maturation  (production of surfactant)

Side effects: immunosuppressive effects

Mechanism: synthetic corticosteroid with increased (GC) topical activity; DOA: 12-36 hours

Treatment:  Useful in dermatology (anti-inflammatory)

Mechanism: synthetic corticosteroid with increased GC and MC activity; DOA: intermediate (12-36hrs)

Side effects: increased BP (salt retention), obesity and fat redistribution, osteoporosis, muscle wasting, peptic ulcers, insomnia, behavioral disorders, increased intraocular pressure, glaucoma, and cataracts, bacterial and mycotic infections, adrenal suppression

a. Chronic: (1)20-30 mg/day hydrocortisone, with increased amounts during periods of stress (2) Fludrocortisone for salt retention (cortisol replacement insufficient). Long-acting synthetics inappropriate

b. Acute: hydrocortisone sodium succinate or phosphate given IV at 100 mg/8 hr with gradual reduction to maintenance dosage over 5 days. Give oral fludrocortisone when cortisone dosage 50mg/day. 

Congenital Adrenal Hyperplasia

1. 21Beta-hydroxylase deficiency

2. 11Beta-hydroxylase deficieny

Therapy

1. increased adrenal androgens causing virilization

2. increased deoxycorticosterone (has MC activity) producing hypertension with hypokalemic alkalosis

For fetuses at risk of virilization, oral dexamethasone. For infants in acute adrenal crisis, hydrocortisone IV. For stable patients, oral hydrocortisone in divided doses (2/3 AM, 1/3 PM) adjusted for normal growth and bone maturation and to prevent virilization. Alternate day therapy with prednisone may suppress ACTH better, without inhibiting growth. Oral fludrocortisone and added salt also neded to maintain BP, rennin, and electrolytes.

Cushing's Syndrome

Therapy

1. High K+ and low Na+ (electrolyte balance)

2. high protein (compensate catabolism)

3. caloric restriction (prevent obesity)

4. calcium, vitamin D, alendronate (prevent osteoporosis)

Mechanism: selectively inhibits 11beta-hydroxylase leads to dec. synthesis of cortisol and aldosterone which in turn leads to inc. ACTH and inc. deoxycorticosterone. Can be detected by inc. 17-hydroxysteroid metabolite in urine.

Treatment: temporary reduction of cortisol to normal levels in patients with severe endogenous Cushing's. Symptomatic relief.

Side-Effects: salt and water retention

Mechanism: competitive inhibitor of cholesterol side chain cleavage enzyme, blocking conversion of cholesterol to pregnenolone and dec. production of all active adrenal and gonadal steroids.

Treatment: in conjunction iwth Metyrapone and Ketoconazole in treating Cushing's due to adrenocortical cancer that do not respond to other therapies

Side-effects: GI disturbances, rash, leukopenia, and agranulocytosis

Mechanism: nonselective inhibitor of the cholesterol side chain cleavage, P450c17, C17, 20-lyase, 3Beta-hydroxysteroid dehydrogenase, and P450c11 enzymes.

Treatment: Palliative for patients with Cushing's Syndrome due to severe causes (adrenocortical hyperplasia and cortisol-secreting tumors)

Side-effects: Hypocorticolism and hepatotoxicity with chronic therapy