Chapter 58: Glcocorticoids In Nonendocrine Disorders Flashcards
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
Glucocorticoid 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”
Glucocorticoid CV 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
Glucocorticoid effects during stress
Physiologic stress (e.g., 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
Glucocorticoid 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
Glucocorticoid 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
Glucocorticoid MOA
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
Glucocorticoid effects on metabolism and electrolytes
More intense with higher doses
Increases in BG
Decrease in protein synthesis
Mobilization of fat deposits
Some Na retention & K loss
Glucocorticoid anti inflammatory and immunosuppressant effects
Major clinical applications of the glucocorticoids stem from their ability to suppress immune responses and inflammation
Glucocorticoid non-endocrine therapeutic uses
Rheumatoid arthritis
Adjunct medication, help with pain and inflammation
Systemic lupus erythematosus
Helps with s/sx
Inflammatory bowel disease
Use in sever cases of CD and UC
Miscellaneous inflammatory disorders
OA, bursitis, tendinitis, gouty artitis, inflammatory disorders of eye
Allergic conditions
Bee stings, drug induced allergies
Adjunct therapy
Not anaphylaxis (need epi)
Asthma
Very effective
Inhaled (min ADR) or PO (ADR, only give if pt has not responded to inhaled)
Dermatologic disorder
Psoriasis, seborrheic dermatitis, contact dermatitis, exfoliaive dermatitis
Mild derma disorders -> topical use
Severe disorders -> systemic script as well
Prevention of respiratory distress syndrome in preterm infants
Single course admin to women who are at risk of preterm labor
Glucocorticoid ADRs
Adrenal insufficiency with prolonged administration
Osteoporosis with prolonged systemic therapy
Infection: PCP (Pneumocystis pneumonia)
Increase susceptibility to infection and mask presence of infetction
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 – 60%
Mild (60%)
insomnia, anxiety, agitation, irritability
Severe (6%)
delirium, hallucinations, depression, euphoria, mania, have been instances of suicide
Cataracts and glaucoma: Long-term glucocorticoid therapy
Open angle glaucoma: ocular HTN develops rapidly, reverse within a couple weeks after d/c med
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 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”
Glucocorticoid drug interactions
Interactions related to potassium loss
Nonsteroidal antiinflammatory drugs
Actions enhanced
PUD commonly seen
Insulin and oral hypoglycemics
Vaccines
Limit effectiveness of vaccine
Glucocorticoids contraindications and precautions
Patients with systemic fungal infections
Those receiving live virus vaccines
Use with caution in pediatric patients and in pregnancy/breastfeeding
Glucocorticoid adrenal suppression
Most dangerous effect of long-term therapy
Adrenal suppression and physiologic stress
Glucocorticoid withdrawal
Taper dosage over 7 days to physiologic range
Switch from multiple doses to single doses in am
Before 9 am –see surge of cortisol
Taper dosage to 50% of physiologic values over 1 mth
Monitor for signs of insufficiency
Glucocorticoid route of admin
Oral, parenteral (IV, IM, subQ), and topical
Individual glucocorticoids differ in three ways:
Biologic half-life
Short Acting -Cortisone, Hydrocortisone
Intermediate Acting -Prednisone, Methylprednisolone, Triamcinnolone
Long Acting -Betamethasone, Dexamethasone
Mineralocorticoid potency
Highest in short acting
Glucocorticoid potency
Anti-inflammatory
Shortest in short acting
Anti inflammatory values relative to dose of hydrocortisone *
