Dexamethasone chemical structure
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Dexamethasone

Dexamethasone is a synthetic member of the glucocorticoid class of hormones. It acts as an anti-inflammatory and immunosuppressant. Its potency is about 40 times that of hydrocortisone. more...

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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.

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

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 nightime 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. Longer versions rely on urine collections on oral dexamethasone over various days.

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, particular 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. Ask your doctor, if you notice them and if they are more than mild.

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Effect of dexamethasone on [[beta].sub.2]-adrenergic desensitization in airway smooth muscle : role of the ARG19 polymorphism
From CHEST, 3/1/03 by Paul E. Moore

Abbreviation: HASM = human airway smooth muscle

We examined the ability of the corticosteroid dexamethasone to inhibit short-term (1 h) and long-term (24 h) [[beta].sub.2]-adrenergic desensitization in cultured human airway smooth muscle (HASM) cells. In cells from 19 individuals studied on 47 experimental days, pretreatment with isoproterenol at [10.sup.-7] mol/L for 1 h or 24 h caused approximately 21% and 77% decreases in the ability of subsequent isoproterenol ([10.sup.-6] mol/L) stimulation to reduce HASM cell stiffness as measured by magnetic twisting cytometry, similar to results we have previously reported. (1) We examined the ability of dexamethasone ([10.sup.-6] mol/L) administered 6 h or 48 h prior to isoproterenol pretreatment, and stratified our results by presence or absence of the Arg19 allele of the [[beta].sub.2]AR upstream peptide, located in the 5'-leader cistron of the [[beta].sub.2]AR gene. This polymorphism has been associated with decreased [[beta].sub.2]AR expression in HASM cells. In cells containing at least one Arg19 allele, dexamethasone did not significantly reverse short-term or long-term desensitization, but in cells without the Arg19 allele, dexamethasone significantly reversed short-term and long-term desensitization (35% and 31%, respectively; p < 0.05 for each). Our results suggest that the Arg19 allele, or other polymorphisms of the promoter of the [[beta].sub.2]AR gene that are in linkage disequilibrium, may affect the ability of dexamethasone to upregulate [[beta].sub.2]AR expression in HASM cells. In addition, our results suggest that [[beta].sub.2]AR genotype may be predictive of corticosteroid responsiveness in individuals with asthma.

REFERENCE

(1) Moore PE, Laporte PD, Abraham JH, et al. Polymorphism of the [[beta].sub.2]-adrenergic receptor gene and desensitization in human airway smooth muscle. Am J Respir Crit Care Med 2000; 162:2117-2124

* From the Departments of Pediatrics and Pharmacology (Dr. Moore and Mr. Calder), Vanderbilt University School of Medicine, Nashville, TN; Physiology Program (Drs. Silverman and Shore), Harvard School of Public Health, Boston, MA; and Department of Medicine (Dr. Panettieri), University of Pennsylvania, Philadelphia, PA.

This abstract is supported by National Institutes of Health grants HL04395, HL56383, HL33009, and HL67663, and the American Lung Association.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Paul E. Moore, MD, Division of Pediatric Pulmonary Medicine, Vanderbilt University School of Medicine, 1161 21st Ave South, S0119 MCN, Nashville, TN 37232-2586

COPYRIGHT 2003 American College of Chest Physicians
COPYRIGHT 2003 Gale Group

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