|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.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
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 Velcade/Revlimid/dexamethasone (VRD).
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 (inflammation 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.
Recreational use dexamethasone as a street drug has been found in Bangladesh, where some sex workers take it to increase body mass for fear of otherwise losing business to competition.
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.
- "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
- Till, John. "Paramedic Clinical Training Aid". Retrieved 30 August 2011.
- Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ (January 2010). "International consensus report on the investigation and management of primary immune thrombocytopenia". Blood 115 (2): 168–86. doi:10.1182/blood-2009-06-225565. PMID 19846889.
- Schmelzeisen R; Frölich Janice C. (1993). "Prevention of postoperative swelling and pain by dexamethasone after operative removal of impacted third molar teeth". Eur. J. Clin. Pharmacol. 44 (3): 275–7. doi:10.1007/BF00271371. PMID 8491244.
- van de Beek D, de Gans J, McIntyre P, Prasad K (2007). "Corticosteroids for acute bacterial meningitis". Cochrane Database Syst Rev (1): CD004405. doi:10.1002/14651858.CD004405.pub2. PMID 17253505.
- Harousseau JL, Attal M, Leleu X, Troncy J, Pegourie B, Stoppa AM, Hulin C, Benboubker L, Fuzibet JG, Renaud M, Moreau P, Avet-Loiseau H (November 2006). "Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study". Haematologica 91 (11): 1498–505. PMID 17043025.
- Chrousos GP, Detera-Wadleigh SD, Karl M (December 1993). "Syndromes of glucocorticoid resistance". Ann. Intern. Med. 119 (11): 1113–24. doi:10.1059/0003-4819-119-11-199312010-00009. PMID 8239231.
- Charmandari E, Kino T, Ichijo T, Chrousos GP (May 2008). "Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder". J. Clin. Endocrinol. Metab. 93 (5): 1563–72. doi:10.1210/jc.2008-0040. PMC 2386273. PMID 18319312.
- Dan L. Longo, Anthony Fauci, Dennis Kasper, Stephen Hauser, J.Jerry Jameson and Joseph Loscalzo, Harrison's Principles of Internal Medicine, 18th edition, p.3055
- Bloom SL, Sheffield JS, McIntire DD, Leveno KJ (April 2001). "Antenatal dexamethasone and decreased birth weight". Obstet Gynecol 97 (4): 485–90. doi:10.1016/S0029-7844(00)01206-0. PMID 11275014.
- Cymerman a, Rock PB (1994). Medical Problems in High Mountain Environments. A Handbook for Medical Officers. USARIEM-TN94-2. US Army Research Inst. of Environmental Medicine Thermal and Mountain Medicine Division Technical Report. Retrieved 2010-09-06.
- Eledrisi MS (April 2007). "First-line therapy for hypertension". Ann. Intern. Med. 146 (8): 615. PMID 17438328.
- Hirvikoski T, Nordenström A, Lindholm T, Lindblad F, Ritzén EM, Wedell A, Lajic S (February 2007). "Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone". J. Clin. Endocrinol. Metab. 92 (2): 542–8. doi:10.1210/jc.2006-1340. PMID 17148562.
- Lajic S, Nordenström A, Hirvikoski T (2011). "Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency". Endocr Dev 20: 96–105. doi:10.1159/000321228. PMID 21164263.
- Dreger A, Feder EK, Tamar-Mattis A (2012). "Prenatal Dexamethasone for Congenital Adrenal Hyperplasia". Journal of Bioethical Inquiry 9 (3): 1–18. doi:10.1007/s11673-012-9384-9. PMC 3416978. PMID 22904609.
- Marciniak B, Patro-Małysza J, Poniedziałek-Czajkowska E, Kimber-Trojnar Z, Leszczyńska-Gorzelak B, Oleszczuk J (May 2011). "Glucocorticoids in pregnancy". Curr Pharm Biotechnol 12 (5): 750–7. PMID 21342122.
- Song (2011). "The effect of combining dexamethasone with ondansetron for nausea and vomiting associated with fentanyl-based intravenous patient-controlled analgesia.". Anaesthesia 66 (4): 263–7. doi:10.1111/j.1365-2044.2011.06648.x. PMID 21401538. Retrieved 24 February 2014.
- "Decadron, Dexamethasone Intensol (dexamethasone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 11 December 2013.
- "PRODUCT INFORMATION DEXMETHSONE® (dexamethasone)" (PDF). TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. 10 August 2010. Retrieved 11 December 2013.
- "PRODUCT INFORMATION DEXMETHSONE INJECTION" (PDF). TGA eBusiness ServicesAspen Pharmacare Australia Pty Ltd. Aspen Pharmacare Australia Pty Ltd. 2 March 2011. Retrieved 11 December 2013.
- "DEXAMETHASONE tablet [ECR Pharmaceuticals]". DailyMed. ECR Pharmaceuticals. December 2010. Retrieved 11 December 2013.
- "Dexamethasone Tablet BP 2.0 mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Merck Sharp & Dohme Limited. 4 December 2013. Retrieved 11 December 2013.
- "Dexamethasone 4.0 mg/ml injection - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Merck Sharp & Dohme Limited. 4 December 2013. Retrieved 11 December 2013.
- Arth GE, Fried J, Johnston DBR, Hoff, DR, Sarett HL, Silber RH, Stoerk HC, Winter CA (1958). "16-Methylated steroids. II. 16α-Methyl analogs of cortisone, a new group of anti-inflammatory steroids. 9α-Halo derivatives". Journal of the American Chemical Society 80 (12): 3161. doi:10.1021/ja01545a063.
- Taub D, Hoffsommer RD, Slates HL, lWendler NL (1958). "16β-Methyl cortical steroids". Journal of the American Chemical Society 80 (16): 4435. doi:10.1021/ja01549a095.
- Dummett, Mark (2010-05-30), "Bangladesh's dark brothel steroid secret", BBC News.
- "Trichlormethiazide and Dexamethasone for veterinary use". Wedgewood Pharmacy. Retrieved 2008-01-23.
- "Understanding Dexamethasone and Other Steroids".
- "Dexamethasone". U.S. National Library of Medicine: Drug Information Portal.