|Systematic (IUPAC) name|
|(8S,9R,10S,11S,13S,14S,16R,17R)-9- Fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17- dodecahydro-3H-cyclopenta[a]phenanthren-3-one|
|Pregnancy cat.||A (AU) C (US)|
|Legal status||Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)|
|Routes||Oral, IV, IM, SC and IO|
|ATC code||A01 C05, D07, D10, H02, R01, S01,S02, S03|
|Mol. mass||392.461 g/mol|
|(what is this?)|
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs that has anti-inflammatory and immunosuppressant effects. It is 25 times more potent than cortisol in its glucocorticoid effect, while having minimal mineralocorticoid effect.
Dexamethasone is used to treat many inflammatory and autoimmune conditions, such as rheumatoid arthritis and bronchospasm. Idiopathic thrombocytopenic purpura, decreased 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.
It is useful to counteract allergic anaphylactic shock, if given in high doses.
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 is often administered before antibiotics in cases of bacterial meningitis. It then 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 to the patient), thus improving prognosis and outcome.
Cancer patients undergoing chemotherapy are given dexamethasone to counteract certain side effects of their antitumor treatment. Dexamethasone can augment the antiemetic effect of 5-HT3 receptor antagonists, such as ondansetron.
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 Adriamycin (doxorubicin) and vincristine (VAD) or VRD- Velcade, Revlimid and Dexamethasone.
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.
High altitude illnesses
Dexamethasone is used in the treatment of high altitude cerebral edema, as well as pulmonary edema. It is commonly carried on mountain climbing expeditions to help climbers deal with altitude sickness.
Dexamethasone has been used as an off-label prenatal treatment for the symptoms of congenital adrenal hyperplasia (CAH) in female fetuses. CAH causes a variety of physical abnormalities, notably ambiguous genitalia in girls. Early prenatal CAH treatment has been shown to reduce some CAH symptoms, but it does not treat the underlying congenital disorder.
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. Administration of prenatal dexamethasone has been the subject of controversy over issues of informed consent and because treatment must predate a clinical diagnosis of CAH in the female fetus.
A study utilizing Freedom of Information Act findings to "detail an extremely troubling off-label medical intervention employed in the U.S. on pregnant women to intentionally engineer the development of their fetuses for sex normalization purposes." Glucocorticoids may alter “fetal programming,” potentially resulting in serious metabolic problems that will not become apparent until adulthood.
The exact incidence of the adverse effects of dexamethasone are not available and 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.
- Increased appetite
- Weight gain
- Impaired skin healing
- Hypertension (high blood pressure)
- Increased risk of infection
- Raised intraocular pressure
- Cataract (in cases of long-term treatment it occurs in approximately 10% of patients)
- Adrenal suppression
- Growth stunting (in children)
- Cushing's syndrome
- Peptic ulcer
- Osteoporosis (brittle bones)
- Diabetes mellitus type 2
- Hyperglycaemia (high blood sugar)
- Pancreatitis (swelling of the pancreas)
- Sodium and water retention
- Abdominal distention
- Corneal or scleral thinning
- Candidiasis (thrush)
- Skin atrophy
- Psychological dependence
- Vertebral collapse
- Oesophageal ulcer
- Intracranial hypertension (long-term treatment)
- Facial plethora
- Muscular atrophy
- Nitrogen depletion due to protein catabolism
- Allergic reactions including anaphylaxis
Sudden withdrawal after long-term treatment with corticosteroids can lead to:
- Uncontrolled infections
- Known hypersensitivity to dexamethasone
- Cerebral malaria
- Systemic fungal infection
- Concurrent treatment with live virus vaccines (including smallpox)
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 which can increase its volume of distribution.
To synthesize dexamethasone, 16β-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 9α-bromo-11β-hydrin derivative, which is then ring-closed to an epoxide. A ring-opening reaction with hydrogen fluoride in tetrahydrofuran gives dexamethasone.
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.
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