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Steroids

In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

Synthetic drugs with corticosteroid-like effect are used in a variety of conditions, ranging from brain tumours to skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisolone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef®) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia.

Synthetic glucocorticoids are used in the treatment of joint pain or inflammation (arthritis), dermatitis, allergic reactions, asthma, hepatitis, lupus erythematosus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency. Topical formulations for treatment of skin or inflammatory bowel disease are available.

Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side effects are hypertension (abnormally high blood pressure), hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema, and metabolic alkalosis.

Dexamethasone

Dexamethasone is a synthetic adrenal corticosteroid. Corticosteroids are natural substances produced by the adrenal glands located adjacent to the kidneys. Corticosteroids have potent anti-inflammatory properties, and are used in a wide variety of inflammatory conditions such as arthritis, colitis, asthma, bronchitis, certain skin rashes, and allergic or inflammatory conditions of the nose and eyes. There are numerous preparations of corticosteroids, including oral tablets, capsules, liquids, topical creams and gels, inhalers and eye drops, and injectable and intravenous solutions. Dexamethasone that is prescribed in oral tablet form is addressed in this article.

Dose

Dosage requirements of corticosteroids vary among individuals and diseases being treated. In general, the lowest possible effective dose is used. Corticosteroids given in multiple doses throughout the day are more effective, but also more toxic, than if the same total dose is given once daily, or every other day. Should be taken with food.

Drug Interactions

Prolonged use of dexamethasone can depress the ability of the body's adrenal glands to produce corticosteroids. Abruptly stopping dexamethasone in these individuals can cause symptoms of corticosteroid insufficiency, with accompanying nausea, vomiting and even shock. Therefore, withdrawal of dexamethasone is usually accomplished by gradual tapering. Gradually tapering dexamethasone not only minimizes the symptoms of corticosteroid insufficiency, it also reduces the risk of an abrupt flare of the disease under treatment.

Dexamethasone and other corticosteroids can mask signs of infection and impair the body's natural immune response to infection. Patients on corticosteroids are more susceptible to infections, and can develop more serious infections than healthy individuals. For instance, chicken pox and measles viruses can produce serious and even fatal illnesses in patients on high doses of dexamethasone. Live virus vaccines, such as small pox vaccine, should be avoided in patients taking high doses of dexamethasone, since even vaccine viruses may cause disease in these patients. Some infectious organisms, such as tuberculosis (TB) and malaria, can remain dormant in a patient for years. Dexamethasone and other corticosteroids can reactivate dormant infections in these patients and cause serious illnesses. Patients with dormant tuberculosis may require anti- TB medications while undergoing prolonged corticosteroid treatment.

By interfering with the patient's immune response, dexamethasone can impede the effectiveness of vaccinations. Dexamethasone can also interfere with the tuberculin (TB) skin test and cause false negative results in patients with dormant tuberculosis infection.

Dexamethasone impairs calcium absorption and new bone formation. Patients on prolonged treatment with dexamethasone and other corticosteroids can develop osteoporosis and an increased risk of bone fractures. Supplemental calcium and vitamin D are encouraged to slow this process of bone thinning. In rare individuals, destruction of large joints can occur while undergoing treatment with dexamethasone or other corticosteroids. These patients experience severe pain in the involved joints, and can require joint replacements. The reason behind such destruction is not clear.

Adverse Reactions

Dexamethasone side effects depend on the dose, the duration and the frequency of administration. Short courses of dexamethasone are usually well tolerated with few and mild side effects. Long term, high doses of dexamethasone will usually produce predictable, and potentially serious side effects. Whenever possible, the lowest effective doses of dexamethasone should be used for the shortest possible length of time to minimize side effects. Alternate day dosing can also help reduce side effects.

Side effects of dexamethasone and other corticosteroids range from mild annoyances to serious irreversible bodily damages. Side effects include fluid retention, weight gain, high blood pressure, potassium loss, headache, muscle weakness, puffiness of and hair growth on the face, thinning and easy bruising of skin, glaucoma, cataracts, peptic ulceration, worsening of diabetes, irregular menses, growth retardation in children, convulsions, and psychic disturbances. Psychic disturbances can include depression, euphoria, insomnia, mood swings, personality changes, and even psychotic behavior. The bone and joint complications of corticosteroids are discussed above in DRUG INTERACTIONS.

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