Corticosteroids
Corticosteroids
Definition
Purpose
Recommended dosage
Precautions
Interactions
Definition
Corticosteroids are a group of natural and synthetic analogs (chemical cousins) of the hormones secreted by the pituitary gland, also known as the hypothalamic-anterior pituitary-adrenocortical (HPA) axis. These analogs include glucocorticoids, which are anti-inflammatory agents with a large number of other functions; mineralocorticoids, which control salt and water balance primarily through action on the kidneys; and corticotropins, which control secretion of hormones by the pituitary gland. First introduced in 1949 for the treatment of rheumatoid arthritis, corticosteroids are widely used in the twenty-first century to treat conditions as varied as asthma, lung infections in AIDS patients, bacterial meningitis, and cancer-related pain.
Purpose
Glucocorticoids have multiple effects, and are used for a large number of conditions. They affect glucose (sugar) utilization and fat metabolism, bone development, and are potent anti-inflammatory agents. They may be used for replacement of natural hormones in patients with pituitary deficiency (Addison’s disease), as well as for a wide number of other conditions including arthritis, asthma, anemia, various cancers, eye disease (uveitis), inflammatory bowel disease, and skin inflammations. Additional uses include inhibition of nausea and vomiting after chemotherapy, treatment of septic shock, treatment of spinal cord injuries, and treatment of hirsutism (excessive hair growth). The choice of drug will vary with the condition.
Cortisone and hydrocortisone, which have both glucocorticoid and mineralocorticoid effects, are the drugs of choice for replacement therapy of natural hormone deficiency. Synthetic compounds, which have greater anti-inflammatory effects and less effect on salt and water balance, are usually preferred for other purposes. These compounds include dexamethasone, which is almost exclusively glucocorticoid in its actions, as well as prednisone, prednisolone, betamethasone, triamcino-lone, and others. Glucocorticoids are formulated in oral dosage forms, topical creams and ointments, oral and nasal inhalations, rectal foams, and ear and eye drops.
Mineralocorticoids control the retention of sodium in the kidneys. In mineralocorticoid deficiency, there is excessive loss of sodium through the kidneys, with resulting water loss. Fludrocortisone (Florinef) is the only drug available for treatment of mineralocorticoid deficiency, and is available only in an oral form.
Corticotropin (ACTH, adrenocorticotropic hormone) stimulates the pituitary gland to release cortisone. A deficiency of corticotropic hormone will have the same effects as a deficiency of cortisone. The hormone, which is available under the brand names Acthar and Actrel, is used for diagnostic testing to determine the cause of a glucocorticoid deficiency. It is rarely used for replacement therapy, however, since direct administration of glucocorticoids may be easier and offers better control over dosages.
Recommended dosage
Dosage of glucocorticoids varies with the specific drug, the route of administration, the condition being treated, and the patient’s individual metabolism.
Fludrocortisone, for use in replacement therapy, is normally dosed at 0.1 mg/day. Some patients require higher doses. It should normally be taken in conjunction with cortisone or hydrocortisone.
ACTH, when used for diagnostic purposes, is given as 10-25 units by intravenous solution over eight hours. A long-acting form, which may be used for replacement therapy, is given by subcutaneous (SC) or intramuscular (IM) injection at a dose of 40-80 units every 24-72 hours.
Precautions
The most significant risk associated with administration of glucocorticoids is suppression of natural corticosteroid secretion. When the artificial hormones are administered, they suppress the secretion of ACTH, which in turn reduces the secretion of the natural hormones. The extent of suppression varies with dose, drug potency, duration of treatment, and individual patient response. While suppression is seen primarily with drugs
KEY TERMS
Addison’s disease— A rare endocrine disorder in which the adrenal gland does not produce enough steroid hormones.
Addisonian crisis— A medical emergency resulting from severe adrenal insufficiency. It can be caused by sudden withdrawal from oral glucocorticoid medications, as well as from damage to the adrenal gland itself. Untreated Addisonian crisis can be fatal.
Cortisol— A corticosteroid hormone produced by the adrenal gland.
Cushing’s syndrome— A condition resulting from excess cortisol in the body, characterized by high blood pressure, a round “moon” face, excessive sweating, thinning of the skin and easy bruising, and the growth of fat pads around the shoulders and back of the neck. It was first described in 1932 by Harvey Cushing, an eminent American surgeon.
Hallucination— A false or distorted perception of objects, sounds, or events that seems real. Hallucinations usually result from drugs or mental disorders.
Hirsutism— Excessive or increased growth of facial or body hair in women resembling the male pattern of hair distribution.
Hormone— A substance that is produced in one part of the body, then travels through the bloodstream to another part of the body where it has its effect.
Hypertension— High blood pressure.
Hypotension— Low blood pressure.
Inflammation— Pain, redness, swelling, and heat that usually develop in response to injury or illness.
Ointment— A thick spreadable substance that contains medicine and is meant to be used on the outside of the body.
Pregnancy category— A system of classifying drugs according to their established risks for use during pregnancy. The classifications are categories A, B, C, D, and X.
administered systemically, it can also occur with topical drugs such as creams and ointments, or drugs administered by inhalation. Abrupt cessation of corticosteroids may result in acute adrenal crisis (Addisonian crisis) which is marked by dehydration with severe vomiting and diarrhea, sudden sharp pain in the abdomen, lower back, or legs, hypotension, convulsions, mental confusion, and loss of consciousness. Acute adrenal crisis is potentially fatal.
Chronic overdose of glucocorticoids leads to Cushingoid syndrome, which is clinically identical to Cushing’s syndrome. The only difference is that in Cushingoid, the excessive steroids are from drug therapy rather than excessive glandular secretion of cortisol. Symptoms vary, but most people have upper body obesity, a rounded “moon” face, increased fat around the neck, and thinning arms and legs. In its later stages, this condition leads to weakening of bones and muscles with rib and spinal column fractures.
The short-term adverse effects of corticosteroids are generally mild, and include indigestion, increased appetite, insomnia, and nervousness. There are also a very large number of infrequent adverse reactions, the most significant of which is drug-induced paranoia. Delirium, depression, menstrual irregularity, and increased hair growth are also possible.
Long-term use of topical glucocorticoids can result in thinning of the skin or permanent damage to the retina of the eye. Oral steroid inhalations may cause fungal overgrowth in the oral cavity. Patients must be instructed to rinse their mouths carefully after each dose.
Corticosteroids are included in pregnancy category C. The pregnancy category system classifies drugs according to their established risks for use during pregnancy. Corticosteroids have caused congenital malformations in animal studies, including cleft palate. Breastfeeding while taking these medications should be avoided.
Because fludrocortisone has glucocorticoid activity as well as mineralocorticoid action, the same hazards and precautions apply to fludrocortisone as to the glucocorticoids. Overdose of fludrocortisone may also cause edema (swelling), hypertension, and congestive heart failure.
Corticotropin has all the same risks as the glucocorticoids. Prolonged use may cause reduced response to the stimulatory effects of corticotropin.
Warnings
Patients with the following conditions should use corticosteroids with caution:
- osteoporosis or any other bone disease
- current or past tuberculosis
- glaucoma or cataracts
- infections of any type (virus, bacteria, fungus, ameba)
- sores in the nose or recent nose surgery (if using nasal spray forms of corticosteroids)
- an underactive or overactive thyroid gland
- liver disease
- stomach or intestine problems
- diabetes
- heart disease
- high blood pressure
- high cholesterol
- kidney disease or kidney stones
- myasthenia gravis
- systemic lupus erythematosus (SLE)
- emotional problems
- skin conditions that cause the skin to be thinner and bruise more easily
Interactions
Corticosteroids interact with many other drugs a patient might take; they reduce the effectiveness of vaccination in some patients. Patients taking barbiturates as sleep medications may need higher doses of corticosteroids. Smoking reduces the effectiveness of inhaled corticosteroids. Patients should inform their doctor about all other medications (both prescription and over-the-counter) they take, and discuss possible interactions.
Resources
BOOKS
Abrams, Anne C., Carol B. Lammon, and Sandra S. Pennington. Clinical Drug Therapy: Rationales for Nursing Practice, 8th ed. Philadelphia: Lippincott Williams and Wilkins, 2007.
Griffith, H. W., and S. Moore. 2001 Complete Guide to Prescription and Nonprescription Drugs. New York: Berkely Publishing Group, 2001.
Neal, Michael J. Medical Pharmacology at a Glance, 5th ed. Malden, MA: Blackwell Publishing, 2005.
PERIODICALS
Bacharier, L. B., H. H. Raissy, L. Wilson, et al. “Long-term Effect of Budesonide on Hypothalamic-Pituitary-Adrenal Axis Function in Children with Mild to Moderate Asthma.” Pediatrics 113 (June 2004): 1693–1699.
Greenwood, B. M. “Corticosteroids for Acute Bacterial Meningitis.” New England Journal of Medicine 357 (December 13, 2007): 2507–2509.
Hubbard, R., et al. “Use of Inhaled Corticosteroids and the Risk of Fracture.” Chest 130 (October 2006): 1082–1088.
Kroon, L. A. “Drug Interactions with Smoking.” American Journal of Health-System Pharmacy 64 (September 15, 2007): 1917–1921.
Rodrigo, G. J. “Rapid Effects of Inhaled Corticosteroids in Acute Asthma: An Evidence-based Evaluation.” Chest 130 (November 2006): 1301–1311.
Zoorob, Roger J., and Dawn Cender. “A Different Look at Corticosteroids.” American Family Physician 58 (August 1998): 443–450.
ORGANIZATIONS
American Academy of Allergy, Asthma and Immunology. 611 East Wells Street, Milwaukee, WI 53202. Telephone: (414) 272-6071. Web site: http://www.aaaai.org (accessed March 11, 2008).
Arthritis Foundation. 1330 West Peachtree Street, Suite 100, Atlanta, GA 30309. (800) 283-7800 or (404) 872-7100. http://www.arthritis.org/index.php (accessed March 11,2008).
Asthma and Allergy Foundation of America. 1125 15th Street NW, Suite 502, Washington, DC 20005. Telephone: (800) 727-8462. Web site: http://www.aafa.org (accessed March 11, 2008).
National Heart, Lung and Blood Institute. National Institutes of Health, P.O. Box 30105, Bethesda, MD 20824-0105. Telephone: (301) 592-8573. http://www.nhlbi.nih.gov/ (accessed March 11, 2008).
U.S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA (1-888-463-6332). http://www.fda.gov/ (accessed March 11, 2008).
Samuel Uretsky, PharmD
Rebecca Frey, PhD
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