Dexamethasone

From Wikipedia, the free encyclopedia - View original article

Dexamethasone
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.commonograph
MedlinePlusa682792
Pregnancy cat.A (AU) C (US)
Legal statusPrescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
RoutesOral, IV, IM, SC andIO
Pharmacokinetic data
Bioavailability80-90%
Protein binding77%
Metabolismhepatic
Half-life190 minutes
ExcretionUrine (65%)
Identifiers
CAS number50-02-2 YesY
ATC codeA01AC02 C05AA09, D07AB19, D10AA03, H02AB02, R01AD03, S01BA01,S02BA06, S03BA01
PubChemCID 5743
DrugBankDB01234
ChemSpider5541 YesY
UNII7S5I7G3JQL YesY
KEGGD00292 YesY
ChEBICHEBI:41879 YesY
ChEMBLCHEMBL384467 YesY
Chemical data
FormulaC22H29FO5 
Mol. mass392.461 g/mol
 N (what is this?)  (verify)
 
  (Redirected from Decadron)
Jump to: navigation, search
Dexamethasone
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.commonograph
MedlinePlusa682792
Pregnancy cat.A (AU) C (US)
Legal statusPrescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
RoutesOral, IV, IM, SC andIO
Pharmacokinetic data
Bioavailability80-90%
Protein binding77%
Metabolismhepatic
Half-life190 minutes
ExcretionUrine (65%)
Identifiers
CAS number50-02-2 YesY
ATC codeA01AC02 C05AA09, D07AB19, D10AA03, H02AB02, R01AD03, S01BA01,S02BA06, S03BA01
PubChemCID 5743
DrugBankDB01234
ChemSpider5541 YesY
UNII7S5I7G3JQL YesY
KEGGD00292 YesY
ChEBICHEBI:41879 YesY
ChEMBLCHEMBL384467 YesY
Chemical data
FormulaC22H29FO5 
Mol. mass392.461 g/mol
 N (what is this?)  (verify)

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.

Therapeutic use[edit]

Anti-inflammatory[edit]

Dexamethasone is used to treat many inflammatory and autoimmune conditions, such as rheumatoid arthritis and bronchospasm.[1] 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.[2]

It is also given in small amounts[3] 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 nameDexacort), 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 themyocardium. 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.[4]

Dexamethasone phosphate for injection

Oncologic uses[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),[5] or a combination of Adriamycin (doxorubicin) and vincristine (VAD) or VRD- Velcade, Revlimid and Dexamethasone.

Endocrine[edit]

Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.[6][7]

In adrenal insufficiency and Addison's disease, dexamethasone is prescribed when the patient does not respond well to prednisone or methylprednisolone.

Obstetrics[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.[8]

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.[9][10]

Off-label use[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.[11][12] 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." [13]Glucocorticoids may alter “fetal programming,” potentially resulting in serious metabolic problems that will not become apparent until adulthood.[11][13][14]Prenatal treatment of female fetuses could prevent those fetuses from becoming lesbians after birth, may make them more likely to engage in "traditionally" female-identified behaviour and careers, and more interested in bearing and raising children.[15] The essay suggests prenatal "dex" treatments constitute the first known attempt to use an in utero method to attempt to reduce the incidence of homosexuality in humans.[16] A medical consensus in 2010 by the Endocrine Society and affiliated organizations indicated prenatal dexamethasone for CAH should be regarded as experimental and should only be used in Institutional Review Board-approved controlled clinical trials at centers large enough to collect meaningful data.[17]

Dexamethasone has also been used in the hope of enhancing sports performance.[18]

Adverse effects[edit]

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.[19][20][21][22][23][24]

Common:

  • Acne
  • Insomnia
  • Vertigo
  • Increased appetite
  • Weight gain
  • Impaired skin healing
  • Depression
  • Euphoria
  • Hypertension (high blood pressure)
  • 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 approximately 10% of patients)

Unknown incidence:

  • Nitrogen depletion due to protein catabolism
  • Allergic reactions including anaphylaxis

Withdrawal[edit]

Sudden withdrawal after long-term treatment with corticosteroids can lead to:[20]

  • Adrenal insufficiency
  • Hypotension (low blood pressure)
  • Fever
  • Myalgia (muscle aches)
  • Arthralgia (joint pain)
  • Rhinitis
  • Conjunctivitis
  • Painful itchy skin nodules
  • Weight loss
  • Death

Contraindications[edit]

Contraindications include:[19][20]

Interactions[edit]

Known drug interactions include:[20]

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 withhydrogen fluoride in tetrahydrofuran gives dexamethasone.[25][26]

Dexamethasone synth.png

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. ^ Till, John. "Paramedic Clinical Training Aid". Retrieved 30 August 2011. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ Eledrisi MS (April 2007). "First-line therapy for hypertension". Ann. Intern. Med. 146 (8): 615. PMID 17438328. 
  11. ^ a b 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. 
  12. ^ 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. 
  13. ^ a b Dreger A, Feder EK, Tamar-Mattis A (2012). "Prenatal Dexamethasone for Congenital Adrenal Hyperplasia". Journal of Bioethical Inquiry: 1–18. doi:10.1007/s11673-012-9384-9. 
  14. ^ 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. 
  15. ^ Dreger A, Feder EJ, Tamar-Mattis A (2010-06-29). "Preventing Homosexuality (and Uppity Women) in the Womb?". Bioethics Forum blog. The Hastings Center. Retrieved 2011-10-11. 
  16. ^ Elton C (2010-06-18). "A Prenatal Treatment Raises Questions of Medical Ethics". TIME. Retrieved 2010-07-05. 
  17. ^ Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC (September 2010). "Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline". J. Clin. Endocrinol. Metab. 95 (9): 4133–60. doi:10.1210/jc.2009-2631. PMC 2936060. PMID 20823466. 
  18. ^ "FIS Doping Control statement on Kowalcyzk". International Ski Federation. 2005-06-13. Retrieved 2006-07-30. 
  19. ^ a b "Decadron, Dexamethasone Intensol (dexamethasone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 11 December 2013. 
  20. ^ a b c d "PRODUCT INFORMATION DEXMETHSONE® (dexamethasone)" (PDF). TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. 10 August 2010. Retrieved 11 December 2013. 
  21. ^ "PRODUCT INFORMATION DEXMETHSONE INJECTION" (PDF). TGA eBusiness ServicesAspen Pharmacare Australia Pty Ltd. Aspen Pharmacare Australia Pty Ltd. 2 March 2011. Retrieved 11 December 2013. 
  22. ^ "DEXAMETHASONE tablet [ECR Pharmaceuticals]". DailyMed. ECR Pharmaceuticals. December 2010. Retrieved 11 December 2013. 
  23. ^ "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. 
  24. ^ "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. 
  25. ^ 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. 
  26. ^ 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. 
  27. ^ "Trichlormethiazide and Dexamethasone for veterinary use". Wedgewood Pharmacy. Retrieved 2008-01-23. 

External links[edit]