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Glucocorticoids

Glucocorticoids

Definition

Glucocorticoids are naturally-produced steroid hormones, or synthetic compounds, that inhibit the process of inflammation.

Purpose

The target of glucocorticoids: inflammation

Glucocorticoids are used to stop the inflammation process. The inflammatory process has evolved in the body for a useful purpose; namely as a defensive reaction to the damage or injury to tissue. By a series of reactions, inflammation is designed to isolate whatever is causing the irritation, help eradicate the presumed invader, and help repair the surrounding damaged tissue.

The hallmarks of inflammation are redness, heat, swelling, and pain . These reactions arise from the various steps in the inflammation pathway. The inflammatory response begins with the expansion of the capillaries, which allows more blood to flow to the target site. Various proteins from the blood then exit the blood and gather at the target site. Ultimately, white blood cells called leukocytes also accumulate at the site of injury. When these processes occur in response to an invader such as a microorganism, this is beneficial for the body, as it can rid the body of a potential problem. However, sometimes the inflammatory response can persist long after the actual problem is gone, or can be maintained if an infection itself becomes chronic, or can be activated by some malfunction in the body's defense mechanisms. Chronic inflammation of this type can cause damage to host tissue. Examples of processes that can produce chronic inflammation are tuberculosis, inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, silicosis, and the continued presence of a foreign body in a wound.

Glucocorticoids can be prescribed to dampen or stop entirely this chronic inflammatory chain of events. Depending on the particular glucocorticoid that is used, inflammation can be affected at different points in the inflammatory pathway.

Description

Some of the various glucocorticoids can be naturally produced in the body. Chemically, these are steroid hormones. They are different from the infamous anabolic steroids that some athletes use to increase muscle mass and strength. Rather, glucocorticoids are catabolic steroids, meaning they are designed to break down compounds. Natural glucocorticoids are produced in the adrenal glands located immediately above the kidneys (the word adrenal derives from "ad," meaning top of, and "renal," meaning kidney). The region of the adrenal glands called the cortex is the site of glucocorticoid manufacture.

Glucocorticoids can also be artificially made, and are usually referred to as glucocorticoid drugs. Examples of glucocorticoids are prednisone, prednisilone, methylprednisilone, dexamethasone, and hydrocortisone. Glucocorticoids are usually taken orally as tablets, capsules, syrup, and liquid, with the exception of hydrocortisone (which is applied as a cream). Most can also be used in cream form, and some can be applied as drops to relieve eye irritations.

Prednisone is the commonly prescribed glucocorticoid because of its high activity. In the body prednisone is transformed by the liver into prednisolone. Prednisolone is equally as effective and is often prescribed by physicians instead of prednisone. Dexamethasone can be prescribed in higher doses than the other glucocorticoids. A common use for this compound is the reduction of nerve swelling following nerve damage or neurosurgery. Depending on the manufacturer, dexamethasone is marketed as Decadron, Dexameth, Dexone, and Hexadrol.

Glucocorticoids and metabolism

As well as affecting the inflammatory process, glucocorticoids have an effect on the utilization of compounds in the body (metabolism). Indeed, the designation glucocorticoid arose from observations that the hormones played a role in the utilization of glucose. In an absence of food, which can be broken down to supply glucose, glucocorticoids act to increase and maintain the normal levels of glucose in the blood. They accomplish this by stimulating glucose production by cells, particularly in the liver, and by enhancing the breakdown of fat in fat tissue. As well, glucocorticoids curb the storage of glucose in cells of the body, which leaves the sugar ready for use.

Glucocorticoids and inflammation

Glucocorticoids are global in their inhibition of the inflammatory response. That is, they act at different stages in the process, and affect all types of inflammatory responses no matter what stimulated the response. The action of glucocorticoids has to do with their structure. Their shape permits them to move across the membrane that surrounds cells in the body, and to be recognized by molecules inside the cell called glucocorticoid receptors. Binding of the particular glucocorticoid to a receptor forms a complex between the two molecules. This complex can enter the nucleus of the cell (the zone where the genetic material is located, and where the two-step process whereby nucleic acid forms the blueprint for the manufacture of the protein building blocks of the cell takes place). Within the nucleus, the complex affects the manufacture of the proteins. The production of some proteins is enhanced while the manufacture of other protein species is diminished. The latter are proteins involved in inflammation and in the release of a normally membrane-bound molecule that acts as a signal for inflammation to begin. The end result is the suppression of inflammation.

Recommended dosage

The prescribed dosages of glucocorticoids vary depending on the compound used and the nature of the patient's condition. Depending on the glucocorticoid, the dose may be taken once a day, over the course of several doses spaced evenly throughout the day, or even every other day.

Precautions

As with any prescription drug, the recommended daily dosage and schedule for the drugs should not be changed independent of a physician's notification. As well, side effects associated with the long-term use of glucocorticoids can occur.

Side effects

Prolonged use of glucocorticoids may cause a number of adverse effects. These include the suppression of the immune system (which makes the person more susceptible to infections), osteoporosis, shifts in the body's fluid balance, skin changes, changes in brain chemistry, and altered behavior.

Dexamethasone can cause loss of appetite, weight loss, stomach upset, vomiting, drowsiness, headache , confusion, fever, joint pain, and peeling skin. Not all side effects will be present in everyone taking dexamethasone.

More severe side effects of glucocorticoid use include development of diabetes (which can occur transiently even with short-term use of the drugs), glaucoma, cataract formation, peptic ulcer, convulsions, and inhibited growth of children. A physician determines whether the potential risks of the particular glucocorticoid outweigh the advantages of its use, and prescribes the minimum dose necessary to achieve the desired effect.

Interactions

Interactions between glucocorticoids and other medications can occur. These include anticoagulants (such as aspirin), digoxin, estrogen, oral contraceptives, phenobarbital , some antibiotics, and even some vitamins.

Resources

BOOKS

Goulding, N. J. Glucocorticoids (Milestones in Drug Therapy). Birkhauser, 2001.

Zuckerman, Eugenia, and Julie R. Inglefinger. Coping with Prednisone and Other Cortisone-Related Medicines: It May Work Miracles, but How Do You Handle the Side Effects? St. Martin's Press, 1998.

OTHER

"Dexamethasone oral." Medline Plus. National Library of Medicine. (May 6, 2004). <http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682792.html>.

"Glucocorticoids Disease Mechanism II: Inflammation." Stanford University. (May 6, 2004). <http://www.stanford.edu/group/hopes/treatmts/antiinflam/I_glucocorticoids.html>

Brian Douglas Hoyle, PhD

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glucocorticoids

glucocorticoids The steroid hormones secreted by the adrenal cortex which regulate carbohydrate metabolism.

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