Dexamethasone

Dexamethasone is a type of corticosteroid medication.[1] 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.[1] In adrenocortical insufficiency, it should be used together with a medication that has greater mineralocorticoid effects such as fludrocortisone.[1] In preterm labor, it may be used to improve outcomes in the baby.[1] It may be taken by mouth, as an injection into a muscle, or intravenously.[1] The effects of dexamethasone are frequently seen within a day and last for about three days.[1]

Dexamethasone
Clinical data
AHFS/Drugs.comMonograph
MedlinePlusa682792
License data
Pregnancy
category
  • AU: A
  • US: C (Risk not ruled out)
    Routes of
    administration    		By mouth, IV, IM, SC, IO
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability80–90%
    Protein binding77%
    MetabolismLiver
    Elimination half-life190 minutes (3.2 hours)
    ExcretionUrine (65%)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    PDB ligand
    CompTox Dashboard (EPA)
    ECHA InfoCard100.000.004
    Chemical and physical data
    FormulaC22H29FO5
    Molar mass392.461 g/mol g·mol−1
    3D model (JSmol)
    Melting point262 °C (504 °F)
     NY (what is this?)  (verify)

    The long-term use of dexamethasone may result in thrush, bone loss, cataracts, easy bruising, or muscle weakness.[1] It is pregnancy category C in the United States meaning use should be based on benefits being predicted to be greater than risks.[2] In Australia, it is category A, meaning it has been frequently used in pregnancy and not been found to cause problems to the baby.[3] It should not be taken when breastfeeding.[1] Dexamethasone has anti-inflammatory and immunosuppressant effects.[1]

    Dexamethasone was first made in 1957 and was approved for medical use in 1961.[4][5] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[6] Dexamethasone is not expensive.[7] In the United States, a month of medication typically costs less than US$25.[1] In India, a course of treatment for preterm labor costs about US$0.5.[7] It is available in most areas of the world.[7] In 2016, it was the 259th most prescribed medication in the United States, with more than a million prescriptions.[8]

    Medical uses
    Dexamethasone

    Anti-inflammatory

    Dexamethasone is used to treat many inflammatory and autoimmune conditions, such as rheumatoid arthritis and bronchospasm.[9] 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.[10]

    It is also given in small amounts[11] 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.[12]

    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, and certain ear drops (can be combined with an antibiotic and an antifungal). Dexamethasone intravitreal steroid implants have been approved by the FDA to treat ocular conditions such as diabetic macular edema, central retinal vein occlusion, and uveitis.[13] Dexamethasone has also been used with antibiotics to treat acute endophthalmitis.[14]

    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.[15]

    Dexamethasone phosphate for injection

    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.[16] 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.[17]

    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),[18] 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.[19][20]

    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.[21]

    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.[22]

    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.[23] Experimental use of dexamethasone in pregnancy for foetal CAH treatment was discontinued in Sweden when one in five cases suffered adverse events.[24]

    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.[25][26]

    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.[27][28]

    Nausea and vomiting

    Intravenous dexamethasone is effective for prevention of nausea and vomiting in people who had surgery and whose post-operative pain was treated with long-acting spinal or epidural spinal opioids.[29]

    The combination of dexamethasone and a 5-HT3 receptor antagonist such as ondansetron is more effective than a 5-HT3 receptor antagonist alone in preventing postoperative nausea and vomiting.[30]

    Dexamethasone, when used as an anti emetic during surgery, does not appear to increase rates of wound infection and it is unclear if it has an effect on wound healing.[31]

    Sore throat

    A single dose of dexamethasone or another steroid speeds improvement of a sore throat.[32]

    Contraindications

    Contraindications of dexamethasone include,[33][34] but not limited to:

    • Uncontrolled infections
    • Known hypersensitivity to dexamethasone
    • Cerebral malaria
    • Systemic fungal infection
    • Concurrent treatment with live virus vaccines (including smallpox)

    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.[33][34][35][36][37][38]

    Common
    • Acne
    • Insomnia
    • Vertigo
    • Increased appetite
    • Weight gain
    • Impaired skin healing
    • Depression
    • Euphoria
    • Hypertension
    • Increased risk of infection
    • Raised intraocular pressure
    • Vomiting
    • Dyspepsia
    • Confusion
    • Amnesia
    • Irritability
    • Nausea
    • Malaise
    • Headaches
    • Cataract (in cases of long-term treatment it occurs in about 10% of patients)

    Unknown frequency

    Withdrawal

    Sudden withdrawal after long-term treatment with corticosteroids can lead to:[34]

    Interactions

    Known drug interactions include:[34]

    Pharmacology

    As a glucocorticoid, dexamethasone is an agonist of the glucocorticoid receptor (GR). It has no mineralocorticoid activity.[39][40]

    Chemistry

    Dexamethasone is a synthetic pregnane corticosteroid and derivative of cortisol (hydrocortisone) and is also known as 1-dehydro-9α-fluoro-16α-methylhydrocortisone or as 9α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione.[41][42]

    Synthesis

    To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative.[43][44] 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.

    Dexamethasone synthesis

    History

    Dexamethasone was first synthesized in 1957.[4] It was introduced for medical use in 1958.[40]

    Society and culture

    Cost

    Dexamethasone is not expensive.[7] In the United States a month of medication typically costs less than US$25.[1] In India a course of treatment for preterm labor is about US$0.5.[7] It is available in most areas of the world.[7]

    Route

    It may be taken by mouth, as a tablet or elixir, as an injection into a muscle, or intravenously.[1]

    Nonmedical use

    Dexamethasone is given in legal Bangladesh brothels to prostitutes not yet of legal age, causing weight gain aimed at making them appear older and healthier to customers and police.[45]

    Dexamethasone and most glucocorticoids are banned by sporting bodies including the World Anti-Doping Agency.[46]

    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.[47]

    See also

    References
    1. "Dexamethasone". The American Society of Health-System Pharmacists. Archived from the original on 2017-09-08. Retrieved Jul 29, 2015.
    2. "Dexamethasone Use During Pregnancy". www.drugs.com. Archived from the original on 17 May 2016. Retrieved 9 June 2016. Dexamethasone is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk.
    3. "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Archived from the original on 8 April 2014. Retrieved 22 April 2014. Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
    4. Rankovic, Zoran; Hargreaves, Richard; Bingham, Matilda (2012). Drug discovery and medicinal chemistry for psychiatric disorders. Cambridge: Royal Society of Chemistry. p. 286. ISBN 9781849733656. Archived from the original on 2016-03-05.
    5. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 485. ISBN 9783527607495.
    6. "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
    7. "DEXAMETHASONE FOR ACCELERATING LUNG MATURATION IN PRETERM BABIES" (PDF). Archived (PDF) from the original on 22 December 2015. Retrieved 29 July 2015.
    8. "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
    9. Till, John. "Paramedic Clinical Training Aid". Archived from the original on 31 March 2012. Retrieved 30 August 2011.
    10. 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.
    11. Schmelzeisen R, Frölich JC (1993). "Prevention of postoperative swelling and pain by dexamethasone after operative removal of impacted third molar teeth". European Journal of Clinical Pharmacology. 44 (3): 275–7. doi:10.1007/BF00271371. PMID 8491244.
    12. "Croup- Diagnosis & Treatment". Mayo Clinic. Retrieved 13 October 2017. Dexamethasone is usually recommended because of its long-lasting effects (up to 72 hours).
    13. Brady CJ, Villanti AC, Law HA, Rahimy E, Reddy R, Sieving PC, Garg SJ, Tang J (2016). "Corticosteroid implants for chronic non-infectious uveitis". Cochrane Database Syst Rev. 2: CD010469. doi:10.1002/14651858.CD010469.pub2. PMC 5038923. PMID 26866343.
    14. Kim CH, Chen MF, Coleman AL (2017). "Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis". Cochrane Database Syst Rev. 2: CD012131. doi:10.1002/14651858.CD012131.pub2. PMC 5419424. PMID 28225198.
    15. Brouwer, Matthijs C.; McIntyre, Peter; de Gans, Jan; Prasad, Kameshwar; van de Beek, Diederik (2010-09-08). "Corticosteroids for acute bacterial meningitis". The Cochrane Database of Systematic Reviews (9): CD004405. doi:10.1002/14651858.CD004405.pub3. ISSN 1469-493X. PMID 20824838.
    16. Roila F, Ballatori E, Ruggeri B, DeAngelis V (May 2000). "Dexamethasone Alone or in Combination with Ondansetron for the Prevention of Delayed Nausea and Vomiting Induced by Chemotherapy". N Engl J Med. 342 (21): 1554–9. doi:10.1056/NEJM200005253422102. PMID 10824073.
    17. Holte K, Kehlet H (Nov 2002). "Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications". J Am Coll Surg. 195 (5): 694–712. doi:10.1016/s1072-7515(02)01491-6. PMID 12437261.
    18. 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.
    19. Chrousos GP, Detera-Wadleigh SD, Karl M (December 1993). "Syndromes of glucocorticoid resistance". Ann. Intern. Med. 119 (11): 1113–24. doi:10.7326/0003-4819-119-11-199312010-00009. PMID 8239231.
    20. 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.
    21. 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
    22. 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.
    23. Time Archived 2016-08-31 at the Wayback Machine
    24. Hirvikoski, Tatja; Nordenström, Anna; Wedell, Anna; Ritzén, Martin; Lajic, Svetlana (June 2012). "Prenatal Dexamethasone Treatment of Children at Risk for Congenital Adrenal Hyperplasia: The Swedish Experience and Standpoint". The Journal of Clinical Endocrinology & Metabolism. 97 (6): 1881–1883. doi:10.1210/jc.2012-1222. PMID 22466333.
    25. 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.
    26. Lajic S, Nordenström A, Hirvikoski T (2011). "Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency". Endocr Dev. Endocrine Development. 20: 96–105. doi:10.1159/000321228. ISBN 978-3-8055-9643-5. PMID 21164263.
    27. 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. Archived from the original on 2009-04-23. Retrieved 2010-09-06. Cite journal requires |journal= (help)
    28. Eledrisi MS (April 2007). "First-line therapy for hypertension". Annals of Internal Medicine. 146 (8): 615. doi:10.7326/0003-4819-146-8-200704170-00021. PMID 17438328.
    29. Grape S, Usmanova I, Kirkham KR, Albrecht E (April 2018). "Intravenous dexamethasone for prophylaxis of postoperative nausea and vomiting after administration of long-acting neuraxial opioids: a systematic review and meta-analysis". Anaesthesia. 73 (4): 480–489. doi:10.1111/anae.14166. PMID 29226971.
    30. Kovac AL (May 2006). "Meta-analysis of the use of rescue antiemetics following PONV prophylactic failure with 5-HT3 antagonist/dexamethasone versus single-agent therapies". Ann Pharmacother. 40 (5): 873–87. doi:10.1345/aph.1G338. PMID 16670361.
    31. Polderman JA, Farhang-Razi V, Van Dieren S, Kranke P, DeVries JH, Hollmann MW, Preckel B, Hermanides J (November 2018). Cochrane Anaesthesia Group (ed.). "Adverse side effects of dexamethasone in surgical patients". The Cochrane Database of Systematic Reviews. 11: CD011940. doi:10.1002/14651858.CD011940.pub3. PMC 6426282. PMID 30480776.
    32. Sadeghirad B, Siemieniuk RA, Brignardello-Petersen R, Papola D, Lytvyn L, Vandvik PO, Merglen A, Guyatt GH, Agoritsas T (September 2017). "Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials". BMJ. 358: j3887. doi:10.1136/bmj.j3887. PMC 5605780. PMID 28931508.
    33. "Decadron, Dexamethasone Intensol (dexamethasone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 12 December 2013. Retrieved 11 December 2013.
    34. "PRODUCT INFORMATION DEXMETHSONE® (dexamethasone)" (PDF). TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. 10 August 2010. Archived from the original on 28 January 2017. Retrieved 11 December 2013.
    35. "PRODUCT INFORMATION DEXMETHSONE INJECTION" (PDF). TGA eBusiness ServicesAspen Pharmacare Australia Pty Ltd. Aspen Pharmacare Australia Pty Ltd. 2 March 2011. Archived from the original on 29 January 2017. Retrieved 11 December 2013.
    36. "DEXAMETHASONE tablet [ECR Pharmaceuticals]". DailyMed. ECR Pharmaceuticals. December 2010. Archived from the original on 13 December 2013. Retrieved 11 December 2013.
    37. "Dexamethasone Tablet BP 2.0 mg – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Merck Sharp & Dohme Limited. 4 December 2013. Archived from the original on 8 May 2015. Retrieved 11 December 2013.
    38. "Dexamethasone 4.0 mg/ml injection – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Merck Sharp & Dohme Limited. 4 December 2013. Archived from the original on 8 May 2015. Retrieved 11 December 2013.
    39. De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Nicolaides NC, Pavlaki AN, Maria Alexandra MA, Chrousos GP (2000). "Glucocorticoid Therapy and Adrenal Suppression". PMID 25905379. Cite journal requires |journal= (help)
    40. Khan MO, Park KK, Lee HJ (2005). "Antedrugs: an approach to safer drugs". Curr. Med. Chem. 12 (19): 2227–39. doi:10.2174/0929867054864840. PMID 16178782.
    41. Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 366–. ISBN 978-1-4757-2085-3. Archived from the original on 15 February 2017.
    42. Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 310–. ISBN 978-3-88763-075-1. Archived from the original on 2017-08-24.
    43. 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): 3161–3163. doi:10.1021/ja01545a063.
    44. 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.
    45. Dummett, Mark (2010-05-30), "Bangladesh's dark brothel steroid secret", BBC News, archived from the original on 2012-02-22.
    46. "Prohibited In-Competition: Glucocorticoids". World Anti-Doping Agency.
    47. "Trichlormethiazide and Dexamethasone for veterinary use". Wedgewood Pharmacy. Archived from the original on 2007-12-12. Retrieved 2008-01-23.
    This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.