Lehne Chapter 72

Question 1

Glucocorticoid Drugs

Answer 1

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

Question 2

Glucocorticoids in ​

Nonendocrine Disorders

Answer 2

Metabolic effects​

Elevates blood glucose​

Promotes storage of glucose in the form of glycogen​

Reduces muscle mass​

Decreases the protein matrix of bone​

Causes thinning of the skin​

Negative nitrogen balance ​

Lipolysis​

Redistribution of fat: “Potbelly,” “moon face,” and “buffalo hump” ​

​Cardiovascular effects​

Low levels of endogenous glucocorticoids: Capillaries become more permeable, vasoconstriction is suppressed, blood pressure falls ​

Glucocorticoids increase circulating red blood cells and polymorphonuclear leukocytes, and decrease lymphocytes, eosinophils, basophils, and monocytes
Effects during stress​

Physiologic stress (for example, surgery, infection, trauma, hypovolemia): Adrenal glands secrete large quantities of glucocorticoids and epinephrine​

Result: Hormones help maintain blood pressure and blood glucose levels​

Insufficient release of glucocorticoids: Hypotension and hypoglycemia occur​

Very severe stress: Glucocorticoid insufficiency can result in circulatory failure and death
Effects on water and electrolytes​

Can exert actions like those of aldosterone​

Can act on the kidney to promote retention of sodium and water while increasing urinary excretion of potassium​

Net result is hypernatremia, hypokalemia, and edema​

Most glucocorticoids used as drugs have very low mineralocorticoid activity​

​Respiratory system in neonates​

During labor and delivery: Adrenal glands of full-term infant release a burst of glucocorticoids​

Effect: Maturation of the lungs​

Preterm infant: Production of glucocorticoids is low​

Preterm infant: High incidence of respiratory distress syndrome

Question 3

Pharmacology of Glucocorticoids

Answer 3

Molecular mechanisms of action are different from those of other drugs​

Glucocorticoid receptors are inside the cell​

Glucocorticoids modulate the production of regulatory proteins rather than signaling pathways
Effects on metabolism and electrolytes​

Anti-inflammatory and immunosuppressant effects​

Major clinical applications of the glucocorticoids stem from their ability to suppress immune responses and inflammation​

Therapeutic uses in nonendocrine disorders​

Rheumatoid arthritis​

Systemic lupus erythematosus​

Inflammatory bowel disease​

Miscellaneous inflammatory disorders
Therapeutic uses in nonendocrine disorders (Cont.)​

Allergic conditions​

Asthma​

Dermatologic disorders​

Neoplasms​

Suppression of allograft rejection​

Prevention of respiratory distress syndrome in preterm infants
Adverse effects​

Adrenal insufficiency with prolonged administration​

Osteoporosis with prolonged systemic therapy​

Infection: PCP (Pneumocystis pneumonia)​

Glucose intolerance: Hyperglycemia and glycosuria​

Myopathy: Proximal muscles of the arms and legs are affected most​
Fluid and electrolyte disturbances: Sodium and water retention and potassium loss ​

Growth retardation: Can suppress growth in children​

Psychologic disturbances
Cataracts and glaucoma: Long-term glucocorticoid therapy​

Peptic ulcer disease: Inhibit prostaglandin synthesis, augment secretion of gastric acid and pepsin, inhibit production of cytoprotective mucus, and reduce gastric mucosal blood flow
Iatrogenic Cushing’s syndrome: Hyperglycemia, glycosuria, fluid and electrolyte disturbances, osteoporosis, muscle weakness, cutaneous striations, lowered resistance to infection; redistribution of fat produces a “potbelly,” “moon face,” and “buffalo hump”​

Use in pregnancy and lactation
Drug interactions​

Interactions related to potassium loss​

Nonsteroidal anti-inflammatory drugs​

Insulin and oral hypoglycemics​

Vaccines
Contraindications and precautions ​

Patients with systemic fungal infections​

Those receiving live virus vaccines​

Use with caution in pediatric patients and in pregnancy/breast-feeding
Adrenal suppression​

Why it can develop​

Adrenal suppression and physiologic stress​

Glucocorticoid withdrawal​

Taper dosage over 7 days​

Switch from multiple doses to single doses​

Taper dosage to 50% of physiologic values​

Monitor for signs of insufficiency

Question 4

Glucocorticoid Routes ​

of Administration

Answer 4

Oral, parenteral (IV, IM, subQ), and topical​

Individual glucocorticoids differ in three ways:​

Biologic half-life​

Mineralocorticoid potency​

Glucocorticoid potency

Question 5

Glucocorticoid Dosage

Answer 5

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 is used only if disorder is life-threatening or has potential to cause permanent disability​

Increased in times of stress​

Gradual weaning​

Alternate-day therapy​

Administer before 0900