Dexamethasone

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Dexamethasone
Dexamethasone structure.svg
Dexamethasone3Dan.gif
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
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682792
Pregnancy cat.
Legal status
Routes Oral, IV, IM, SC and IO
Pharmacokinetic data
Bioavailability 80-90%
Protein binding 77%
Metabolism hepatic
Half-life 190 minutes
Excretion Urine (65%)
Identifiers
CAS number 50-02-2 YesY
ATC code A01AC02 C05AA09, D07AB19, D10AA03, H02AB02, R01AD03, S01BA01,S02BA06, S03BA01
PubChem CID 5743
DrugBank DB01234
ChemSpider 5541 YesY
UNII 7S5I7G3JQL YesY
KEGG D00292 YesY
ChEBI CHEBI:41879 YesY
ChEMBL CHEMBL384467 YesY
Chemical data
Formula C22H29FO5 
Mol. mass 392.461 g/mol
 N (what is this?)  (verify)

Dexamethasone is a type of steroid medication. It 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 for the treatment of many conditions including: rheumatologic problems, a number of skin diseases such as erythema multiforme, severe allergies, asthma, chronic obstructive lung disease, croup, cerebral edema, in addition to other medications in tuberculosis and a number of other infectious diseases among others.[1]

It is pregnancy category C in the United States and class A in Australia meaning that it has been frequently used in pregnancy and not been found to cause problems for the baby.[1][2]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[3]

Medical use[edit]

Anti-inflammatory[edit]

Dexamethasone is used to treat many inflammatory and autoimmune conditions, such as rheumatoid arthritis and bronchospasm.[4] 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.[5]

It is also given in small amounts[6] 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 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 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.[7]

Dexamethasone phosphate for injection

Cancer[edit]

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),[8] or a combination of adriamycin (doxorubicin) and vincristine or velcade/revlimid/dexamethasone.

Endocrine[edit]

Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.[9][10]

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.[11]

Pregnancy[edit]

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.[12]

High-altitude illnesses[edit]

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.[13][14]

Other[edit]

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.[15][16] 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.

Synergism[edit]

Dexamethasone and ondansetron are more effective than ondansetron alone in preventing postoperative nausea and vomiting.[17]

Adverse effects[edit]

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.[18][19][20][21][22][23]

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 incidence:

Withdrawal[edit]

Sudden withdrawal after long-term treatment with corticosteroids can lead to:[19]

Contraindications[edit]

Contraindications include:[18][19]

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

Interactions[edit]

Known drug interactions include:[19]

Synthesis[edit]

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.

Dexamethasone synthesis:[24][25]

Nonmedical use[edit]

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.[26]

Veterinary use[edit]

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.[27]

References[edit]

  1. ^ a b "Dexamethasone". The American Society of Health-System Pharmacists. Retrieved Sep 26, 2014. 
  2. ^ "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Retrieved 22 April 2014. 
  3. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  4. ^ Till, John. "Paramedic Clinical Training Aid". Retrieved 30 August 2011. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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
  12. ^ 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. 
  13. ^ 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. 
  14. ^ Eledrisi MS (April 2007). "First-line therapy for hypertension". Ann. Intern. Med. 146 (8): 615. doi:10.7326/0003-4819-146-8-200704170-00021. PMID 17438328. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 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. 
  18. ^ a b "Decadron, Dexamethasone Intensol (dexamethasone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 11 December 2013. 
  19. ^ a b c d "PRODUCT INFORMATION DEXMETHSONE® (dexamethasone)" (PDF). TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. 10 August 2010. Retrieved 11 December 2013. 
  20. ^ "PRODUCT INFORMATION DEXMETHSONE INJECTION" (PDF). TGA eBusiness ServicesAspen Pharmacare Australia Pty Ltd. Aspen Pharmacare Australia Pty Ltd. 2 March 2011. Retrieved 11 December 2013. 
  21. ^ "DEXAMETHASONE tablet [ECR Pharmaceuticals]". DailyMed. ECR Pharmaceuticals. December 2010. Retrieved 11 December 2013. 
  22. ^ "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. 
  23. ^ "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. 
  24. ^ 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. 
  25. ^ 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. 
  26. ^ Dummett, Mark (2010-05-30), Bangladesh's dark brothel steroid secret, BBC News. 
  27. ^ "Trichlormethiazide and Dexamethasone for veterinary use". Wedgewood Pharmacy. Retrieved 2008-01-23. 

External links[edit]