Dexamethasone

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. It acts as an anti-inflammatory and immunosuppressant. Its potency is about 20-30 times that of hydrocortisone and 4-5 times of prednisone.

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Therapeutic use

Dexamethasone is used to treat many inflammatory and autoimmune conditions, e.g., rheumatoid arthritis. It is also given to cancer patients undergoing chemotherapy, to counteract certain side-effects of their antitumor treatment. Dexamethasone can augment the antiemetic effect of 5-HT₃ receptor antagonists like ondansetron. It is also given in small amounts (usually 5-6 tablets) before and/or after some forms of dental surgery, such as the extraction of the wisdom teeth, an operation which often leaves the patient with puffy, swollen cheeks.

In brain tumours (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures. Dexamethasone is also given in cord compression where a tumor is compressing the spinal cord.

Dexamethasone is also used in certain hematological malignancies, especially in the treatment of multiple myeloma, in which dexamethasone is given alone or together with thalidomide (thal-dex) or a combination of adriamycin and vincristine (VAD). It is injected into the heel when treating plantar fasciitis, sometimes in conjunction with triamcinolone acetonide.

It is useful to counteract allergic shock, if given in high doses. It is present in certain eye drops and as a nasal spray (trade name Dexacort).

Dexamethasone can be used in the context of congenital adrenal hyperplasia, to prevent virilisation of a female fetus. If one or both parents are carriers of mutations to the CYP21A gene, the mother may start dexamethasone treatment within 7 weeks of conception. At the 12th week, a chorionic villus sample will determine whether the fetus is male (in which case the dexamethasone is stopped) or female. Subsequent DNA analysis can then reveal whether the female fetus is a carrier of the mutation, in which case dexamethasone treatment must continue until birth. The side-effects for the mother can be severe and the long-term impact on the child is not clear. Dexamethasone is also given to women at risk of delivering prematurely in order to promote maturation of the fetus' lungs. This has been associated with low birth weight, although not with increased rates of neonatal death.^[1]

Dexamethasone is used in the treatment of high altitude cerebral edema as well as Pulmonary Oedema. It is commonly carried on mountain climbing expeditions to help climbers deal with altitude sickness. ^[2]

Diagnostic use

Dexamethasone is also used in a diagnostic context, namely in its property to suppress the natural pituitary-adrenal axis. Patients presenting with clinical signs of glucocorticoid excess (Cushing's syndrome) are generally diagnosed by a 24-hour urine collection for cortisol or by a dexamethasone suppression test. During the latter, the response of the body to a high dose of glucocorticoids is monitored. Various forms are performed. In the most common form, a patient takes a nighttime dose of either 1 or 4 mg of dexamethasone, and the serum cortisol levels are measured in the morning. If the levels are relatively high (over 5 µg/dl or 150 nmol/l), then the test is positive and the patient has an autonomous source of either cortisol or ACTH, indicating Cushing's syndrome where the tumor does not have a feedback mechanism. If ACTH levels are lowered by at least 50%, this would indicate Cushing's Disease, since the pituitary adenoma has a feedback mechanism that has been reset to a higher level of cortisol. Longer versions rely on urine collections on oral dexamethasone over various days.

Veterinary use

Combined with marbofloxacin and clotrimazole, dexamethasone is available under the name Aurizon , CAS number 115550-35-1, and used to treat difficult ear infections, especially in dogs.

Contraindications

Some of these contraindications are relative:

• Existing gastrointestinal ulceration
• Cushing's syndrome
• Severe forms of heart insufficiency
• Severe hypertension
• Uncontrolled diabetes mellitus
• Systemic tuberculosis
• Severe systemic viral, bacterial, and fungal infections
• Preexisting wide angle glaucoma
• Osteoporosis

Side effects

If dexamethasone is given orally or by injection (parenteral) over a period of more than a few days, side-effects common to systemic glucocorticoids may occur. These may include:

• Stomach upset, increased sensitivity to stomach acid to the point of ulceration of esophagus, stomach, and duodenum
• Increased appetite leading to significant weight gain
• A latent diabetes mellitus often becomes manifest. Glucose intolerance is worsened in patients with preexisting diabetes.
• Immunsuppressant action, particularly if given together with other immunosuppressants such as ciclosporine. Bacterial, viral, and fungal disease may progress more easily and can become life-threatening. Fever as a warning symptom is often suppressed.
• Psychiatric disturbances, including personality changes, irritability, euphoria, mania
• Osteoporosis under long term treatment, pathologic fractures (e.g., hip)
• Muscle atrophy, negative protein balance (catabolism)
• Elevated liver enzymes, fatty liver degeneration (usually reversible)
• Cushingoid (syndrome resembling hyperactive adrenal cortex with increase in adiposity, hypertension, bone demineralization, etc.)
• Depression of the adrenal gland is usually seen, if more than 1.5 mg daily are given for more than three weeks to a month.
• Hypertension, fluid and sodium retention, edema, worsening of heart insufficiency (due to mineral corticoid activity)
• Dependence with withdrawal syndrome is frequently seen.
• Increased intraocular pressure, certain types of glaucoma, cataract (serious clouding of eye lenses)
• Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound-healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
• Allergic reactions (though infrequently): Anaphylactoid reaction, anaphylaxis, angioedema. (Highly unlikely, since dexamethasone is given to prevent anaphylactoid reactions.)

Other side-effects have been noted, and should cause concern if they are more than mild.

The short time treatment for allergic reaction, shock, and diagnostic purposes usually does not cause serious side effects.

Interactions

• NSAIDs and alcohol: increased risk of gastrointestinal ulceration
• Mineralocorticoids: increased risk of hypertension, edema and heart problems
• Oral antidiabetic drugs and insulin: antidiabetic therapy may have to be adjusted

Other interactions (with certain antibiotics, estrogens, ephedrine, digoxin) are known.

Dosage

• Shock: 4 to 8 mg intravenously initially, repeat if necessary to a total dose of 24 mg.
• Autoimmune diseases and inflammations: longterm therapy with 0.5 to 1.5 mg oral per day. Avoid more than 1.5 mg daily, because serious side effects are more frequently encountered with higher doses.
• Adjuvant to or part of chemotherapy: individual schedule
• Diagnostic purposes: special schedule

Sports doping

In 2005, Polish cross country skier Justyna Kowalczyk was disqualified from the Under 23 (U23) OPA (Alpine nations) Intercontinential Competition in Germany and issued a 2-year suspension for her doping offenses on dexamethasone.^[3] This was eventually reduced to one year during 2005 and later rescinded by the Court of Arbitration for Sport in December 2005.^[4] She would later earn a bronze in the women's 30 km freestyle mass start at the 2006 Winter Olympics in Turin.

References

1. ^ Bloom SL, Sheffield JS, McIntire DD, Leveno KJ (2001). "Antenatal dexamethasone and decreased birth weight". Obstet Gynecol 97 (4): 485–90. PMID 11275014.
2. ^ COMMENTS AND RESPONSES Reducing the Incidence of High-Altitude Pulmonary Edema Annals of Internal Medicine PDF
3. ^ June 13, 2005 FIS Doping Control statement on Kowalcyzk (Digitized version). - Accessed July 30, 2006
4. ^ December 14, 2005 FIS Newsflash on her overturned suspension (Digitized version). - Accessed July 30, 2006