1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 72 Glucocorticoids in Nonendocrine Disorders

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.2 Glucocorticoid Drugs  Also known as corticosteroids and nearly identical to steroids produced by the adrenal cortex  Physiologic effects (low doses)  Modulation of glucose metabolism in adrenocortical insufficiency  Pharmacologic effects (high doses)  Suppression of inflammation

3. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.3 Glucocorticoids in Nonendocrine Disorders  Glucocorticoid physiology  Metabolic effects  Cardiovascular effects  Effects during stress  Effects on water and electrolytes  Respiratory system in neonates

4. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.4 Pharmacology of Glucocorticoids  Molecular mechanisms of action different from those of other drugs  Glucocorticoid receptors are inside the cell  Glucocorticoids modulate the production of regulatory proteins vs. signaling pathways

5. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 Pharmacology of Glucocorticoids  Effects on metabolism and electrolytes  Anti-inflammatory and immunosuppressant effects  Therapeutic uses in nonendocrine disorders  Rheumatoid arthritis  Systemic lupus erythematosus  Inflammatory bowel disease  Miscellaneous inflammatory disorders

6. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.6 Pharmacology of Glucocorticoids  Therapeutic uses in nonendocrine disorders (cont’d)  Allergic conditions  Asthma  Dermatologic disorders  Neoplasms  Suppression of allograft rejection  Prevention of respiratory distress syndrome

7. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.7 Fig. 72–1. Feedback regulation of glucocorticoid synthesis and secretion.

8. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Pharmacology of Glucocorticoids  Adverse effects  Adrenal insufficiency  Osteoporosis and resultant fractures  Infection  Glucose intolerance  Myopathy  Fluid and electrolyte disturbances  Growth retardation  Psychologic disturbances

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.9 Pharmacology of Glucocorticoids  Adverse effects (cont’d)  Cataracts and glaucoma  Peptic ulcer disease  Iatrogenic Cushing’s syndrome  Use in pregnancy and lactation  Drug interactions  Interactions related to potassium loss  Nonsteroidal anti-inflammatory drugs  Insulin and oral hypoglycemics  Vaccines

10. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 Pharmacology of Glucocorticoids  Contraindications  Patients with systemic fungal infections  Those receiving live virus vaccines  Use with caution in pediatric patients and in pregnancy/breast-feeding

11. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.11 Pharmacology of Glucocorticoids  Adrenal suppression  Why it can develop  Adrenal suppression and physiologic stress  Glucocorticoid withdrawal Taper the dosage over 7 days Taper the dosage over 7 days Switch from multiple doses to single doses Switch from multiple doses to single doses Taper the dosage to 50% of physiologic values Taper the dosage to 50% of physiologic values Monitor for signs of insufficiency Monitor for signs of insufficiency

12. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Glucocorticoid Routes of Administration  Oral, parenteral (IV, IM, subQ), and topical  Individual glucocorticoids differ in three ways:  Biologic half-life  Mineralocorticoid potency  Glucocorticoid potency

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.13 Glucocorticoid Dosage  Highly individualized  Determined empirically (trial and error)  No immediate threat—start low and slow  Immediate threat—start high; decrease as possible  Long-time use—smallest effective amount  Prolonged treatment with high doses only if disorder is life-threatening or has potential to cause permanent disability  Increased in times of stress  Gradual weaning  Alternate-day therapy