Glucocorticoids are naturally-produced steroid hormones, or synthetic compounds, that inhibit the process of inflammation.
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.
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.
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.
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.
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 between glucocorticoids and other medications can occur. These include anticoagulants (such as aspirin), digoxin, estrogen, oral contraceptives, phenobarbital , some antibiotics, and even some vitamins.
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"Dexamethasone oral." Medline Plus. National Library of Medicine. (May 6, 2004). <http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682792.html>.
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Brian Douglas Hoyle, PhD
Glucocorticoids are a group of steroid compounds that are both naturally occurring and synthetically manufactured. They act as an anti-inflammatory and as agents that suppress the immune system. Also known as corticosteroids, these agents generally act to suppress the body's ability to cause inflammation both upon the surface of the skin as well as in that occurring in muscles and joints.
The process by which glucocorticoids are released within the body begins in the adrenal cortex of the brain. It is there that special hormones (providing chemical signals to the body) are released to trigger the production of one of three materials: peptides, proteins, or steroids. Steroids are a multiple-ringed molecule, closely related to the fats ingested by the body; vitamin D, cholesterol, and the female hormone estrogen are all steroids. The steroids produced through this process within the body are not to be confused with anabolic steroids, artificially manufactured drugs used in the building of muscle mass.
The signal from the adrenal cortex that ultimately results in the release of a cortisol steroid is intended to provide anti-inflammatory relief to the portion of the body that needs it. Cortisone is delivered through the bloodstream to the affected area, and it will continue to be produced by the body for so long as inflammation is signaled to the adrenal cortex.
Glucocorticoids have been synthesized for use as anti-inflammatory medications for many years. The best known of the synthetics are prednisone and cortisone; each has a similar function. Prednisone is very similar in its chemical composition to that of cortisone, but often has a more pronounced and immediate effect than cortisone. Prednisone is commonly prescribed to combat inflammation associated with arthritis, bursitis as it may occur in any joint of the body that is constructed with a cushioning fluid sac known as the bursa, and synovitis, the inflammation of the fluid structures surrounding joints such as the ankle. Prednisone is administered in a tablet form. The usage of prednisone may lead to pronounced side effects, including mood changes, increased appetite, a heightened risk of infection due to the negative impact on the immune system, and fluid retention. In the longer term, prednisone can contribute to osteoporosis, as it may interfere in the proper conversion of calcium to bone formation.
Cortisone has a long history of specific sports injury applications. Injuries that are caused by overuse or repetitive strain have commonly been targeted for cortisone therapy. The cortisone used is a synthetic version, and is typically administered by way of injection directly into the affected area. The cortisone provided in an injection, due to the concentrated amount delivered in contrast to that manufactured naturally in the body, is intended to have a pronounced and immediate anti-inflammatory effect. Cortisone does not possess any analgesic, or pain-killing, properties. Cortisone is often administered to counter the inflammation caused by the following injuries and conditions: arthritis (usually caused by damage or other wearing away of the cartilage lining in a joint); shoulder bursitis (caused by an inflammation of the bursa); finger, wrist, and elbow strains, including carpal tunnel syndrome; and knee and ankle sprains.
Cortisone also has a number of negative implications, especially in situations of long-term usage. Cortisone will tend to interfere in the vitamin D/calcium absorption process, fundamental to bone and tooth maintenance. This interference promotes general bone weakness. Cortisone also limits the development of collagen in bones. There are also concerns held throughout the sports medicine community that, when cortisone is injected into a joint already loosened by ligament damage, the joint will continue to create stresses on the remaining cartilage and accelerate further joint damage at the expense of immediate anti-inflammatory relief.
As importantly, long-term use of any anti-inflammatory may create a false sense of security on the part of an athlete. Medications such as cortisone are not a cure for an underlying structural problem that exists in a joint. If the anti-inflammatory becomes a substitute for corrective treatment of a joint injury, the damage to the joint may be increased. This concern is particularly acute in circumstances where the original injury was caused by repetitive strain such as pitching a baseball. The use of an anti-inflammatory, injected to permit the athlete to overcome the limitations of the inflammatory condition, may also accompany adjustments made by the athlete in his or her motion or delivery. This combination will sometimes result in the stresses of the repetitive motion to be redirected into another part of the immediate musculoskeletal structure, causing separate strain.