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