Dexamethasone is a type of corticosteroid medication. It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, and along with antibiotics in tuberculosis. In adrenocortical insufficiency, it should be used together with a medication that has greater mineralocorticoid effects such as fludrocortisone. In preterm labor, it may be used to improve outcomes in the baby. It may be taken by mouth, as an injection into a muscle, or intravenously. The effects of dexamethasone are frequently seen within a day and last for about three days.
The long-term use of dexamethasone may result in thrush, bone loss, cataracts, easy bruising, or muscle weakness. It is pregnancy category C in the United States meaning use should be based on benefits being predicted to be greater than risks. In Australia, it is category A, meaning it has been frequently used in pregnancy and not been found to cause problems to the baby. It should not be taken when breastfeeding. Dexamethasone has anti-inflammatory and immunosuppressant effects.
Dexamethasone was first made in 1957. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Dexamethasone is not expensive. In the United States a month of medication typically costs less than 25 USD. In India a course of treatment for preterm labor is about 0.5 USD. It is available in most areas of the world.
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Medical use
Anti-inflammatory
Dexamethasone is used to treat many inflammatory and autoimmune conditions, such as rheumatoid arthritis and bronchospasm. Idiopathic thrombocytopenic purpura, a decrease in numbers of platelets due to an immune problem, responds to 40 mg daily for four days; it may be administered in 14-day cycles. It is unclear whether dexamethasone in this condition is significantly better than other glucocorticoids.
It is also given in small amounts 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.
Dexamethasone is commonly given as a treatment for croup in children, as a single dose can reduce the swelling of the airway to improve breathing and reduce discomfort.
It is injected into the heel when treating plantar fasciitis, sometimes in conjunction with triamcinolone acetonide.
It is useful to counteract allergic anaphylactic shock, if given in high doses.
It is present in certain eye drops - particularly after eye surgery - and as a nasal spray (trade name Dexacort), and certain ear drops (Sofradex, when combined with an antibiotic and an antifungal). Dexamethasone intravitreal steroid implants (trade name Ozurdex) have been approved by the FDA to treat ocular conditions such as diabetic macular edema, central retinal vein occlusion, and uveitis. Dexamethasone has also been used with antibiotics to treat acute endophthalmitis.
Dexamethasone is used in transvenous screw-in cardiac pacing leads to minimize the inflammatory response of the myocardium. The steroid is released into the myocardium as soon as the screw is extended and can play a significant role in minimizing the acute pacing threshold due to the reduction of inflammatory response. The typical quantity present in a lead tip is less than 1.0 mg.
Dexamethasone may be administered before antibiotics in cases of bacterial meningitis. It acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics (bacterial death releases proinflammatory mediators that can cause a response which is harmful), thus reducing hearing loss and neurological damage.
Cancer
People with cancer undergoing chemotherapy are often given dexamethasone to counteract certain side effects of their antitumor treatments. Dexamethasone can increase the antiemetic effect of 5-HT3 receptor antagonists, such as ondansetron. The exact mechanism of this interaction is not well-defined, but it has been theorized that this effect may be due to, among many other causes, inhibition of prostaglandin synthesis, anti-inflammatory effects, immunosuppressive effects, decreased release of endogenous opioids, or a combination of the aforementioned.
In brain tumors (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures. It is also given in cord compression, where a tumor is compressing the spinal cord.
Dexamethasone is also used as a direct chemotherapeutic agent in certain haematological malignancies, especially in the treatment of multiple myeloma, in which dexamethasone is given alone or in combination with other chemotherapeutic drugs, including most commonly with thalidomide (Thal-dex), lenalidomide, bortezomib (Velcade, Vel-dex), or a combination of doxorubicin (Adriamycin) and vincristine or bortezomib/lenalidomide/dexamethasone.
Endocrine
Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.
In adrenal insufficiency and Addison's disease, dexamethasone is prescribed when the patient does not respond well to prednisone or methylprednisolone.
It can be used in congenital adrenal hyperplasia in older adolescents and adults to suppress ACTH production. It is typically given at night.
Pregnancy
Dexamethasone may be given to women at risk of delivering prematurely to promote maturation of the fetus' lungs. This has been associated with low birth weight, although not with increased rates of neonatal death.
Dexamethasone has also been used during pregnancy as an off-label prenatal treatment for the symptoms of congenital adrenal hyperplasia (CAH) in female babies. CAH causes a variety of physical abnormalities, notably ambiguous genitalia. Early prenatal CAH treatment has been shown to reduce some CAH symptoms, but it does not treat the underlying congenital disorder. This use is controversial: it is inadequately studied, only around one in ten of the foetuses of women treated are at risk of the condition, and serious adverse events have been documented. Experimental use of dexamethasone in pregnancy for foetal CAH treatment was discontinued in Sweden when one in five cases suffered adverse events.
A small clinical trial found long-term effects on verbal working memory among the small group of children treated prenatally, but the small number of test subjects means the study cannot be considered definitive.
High-altitude illnesses
Dexamethasone is used in the treatment of high-altitude cerebral edema (HACE), as well as high-altitude pulmonary edema (HAPE). It is commonly carried on mountain-climbing expeditions to help climbers deal with complications of altitude sickness.
Vomiting
Dexamethasone and ondansetron are more effective than ondansetron alone in preventing postoperative nausea and vomiting.
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Adverse effects
The exact incidence of the adverse effects of dexamethasone are not available, hence estimates have been made as to the incidence of the adverse effects below based on the adverse effects of related corticosteroids and on available documentation on dexamethasone.
Common:
Unknown incidence:
Withdrawal
Sudden withdrawal after long-term treatment with corticosteroids can lead to:
Contraindications
Contraindications include, but not limited to:
- Uncontrolled infections
- Known hypersensitivity to dexamethasone
- Cerebral malaria
- Systemic fungal infection
- Concurrent treatment with live virus vaccines (including smallpox)
Interactions
Known drug interactions include:
- Inducers of hepatic microsomal enzymes such as barbiturates, phenytoin, and rifampicin can reduce the half-life of dexamethasone.
- Cotreatment with oral contraceptives can increase its volume of distribution.
Pharmacology
As a glucocorticoid, dexamethasone is an agonist of the glucocorticoid receptor (GR).
Chemistry
Dexamethasone is a synthetic pregnane corticosteroid and derivative of cortisol (hydrocortisone) and is also known as 1-dehydro-9?-fluoro-16?-methylhydrocortisone or as 9?-fluoro-11?,17?,21-trihydroxy-16?-methylpregna-1,4-diene-3,20-dione.
Synthesis
To synthesize dexamethasone, 16?-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative. This is then reacted with a source of hypobromite, such as basic N-bromosuccinimide, to form the 9?-bromo-11?-hydrin derivative, which is then ring-closed to an epoxide. A ring-opening reaction with hydrogen fluoride in tetrahydrofuran gives dexamethasone.
Bear in mind that for the route starting from 16?-methylprednisolone acetate, the product is 16?-methyl instead of ?
Society and culture
Cost
Dexamethasone is not expensive. In the United States a month of medication typically costs less than 25 USD. In India a course of treatment for preterm labor is about 0.5 USD. It is available in most areas of the world.
Nonmedical use
Dexamethasone is given in legal Bangladeshi brothels to prostitutes not yet of legal age, causing weight gain aimed at making them appear healthier and older to customers and police.
Dexamethasone is a banned substance by some sporting bodies. In November 2014, the world's number one badminton player Lee Chong Wei was banned by the Badminton World Federation for testing positive for the drug, although he denied using any banned substances.
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. It can also be combined with trichlormethiazide to treat horses with swelling of distal limbs and general bruising.
Source of the article : Wikipedia
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