Dexamethasone is a fluorinated glucocorticoid medication[ used to treat rheumatology, a number of , severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, cerebral edema, eye pain following eye surgery, SVC syndrome (a complication of some forms of cancer),][ In adrenocortical insufficiency, it may be used in combination with a mineralocorticoid medication such as fludrocortisone.][ In preterm labor, it may be used to improve outcomes in the baby.][ It may be given by mouth, as an injection into a muscle, as an intravenously, as a topical cream or ointment for the skin or as a topical ophthalmic solution to the eye.][ The effects of dexamethasone are frequently seen within a day and last for about three days.]
The long-term use of dexamethasone may result in candidiasis, bone loss, , easy bruising, or muscle weakness.[ It is in pregnancy category C in the United States, meaning that it should only be used when the benefits are predicted to be greater than the risks.][ Dexamethasone has anti-inflammatory and immunosuppressant effects.][
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Dexamethasone was first synthesized in 1957 by Philip Showalter Hench and was approved for medical use in 1958.
Medical uses
Anti-inflammatory
Dexamethasone is used to treat many inflammation and autoimmune disorders, such as rheumatoid arthritis and bronchospasm.
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 that often causes puffy, swollen cheeks.
Dexamethasone is commonly given as a treatment for croup in children.
Dexamethasone is sometimes injected into the heel when treating plantar fasciitis or heel pain, sometimes in conjunction with triamcinolone acetonide. There is no evidence that this treatment helps in the long term, however, dexamethasone may provide short-term pain relief.
It may be useful to counteract anaphylaxis, however this is not usually recommended by clinical guidelines.
It is present in certain – 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 US Food and Drug Administration (FDA) to treat ocular conditions such as diabetic macular edema, central retinal vein occlusion, and uveitis. However, the evidence is poor quality relating to the treatment of uveitis, with the potential side effects (cataract progression and raised intraocular pressure) being significant, and the benefits not certainly greater than standard treatment.
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. Gram-negative bacteria — to which the causative agent of bacterial meningitis, neisseria meningitidis, belongs — have highly immunogenic lipopolysaccharides as a component of their cell membrane and trigger a strong inflammatory response. Pre-administration of dexamethasone before the administration of antibiotics acts to reduce that response, thus reducing hearing loss and neurological damage.
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.
In (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures.
Dexamethasone is also used as a direct chemotherapeutic agent in certain hematological 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 doxorubicin (Adriamycin) and vincristine or bortezomib/lenalidomide/dexamethasone.
COVID-19
Dexamethasone is recommended by the National Health Service in the UK and the National Institutes of Health (NIH) in the US for people with COVID-19 who need either mechanical ventilation or oxygen therapy (without ventilation).
The Infectious Diseases Society of America (IDSA) guideline panel suggests the use of glucocorticoids for people with severe COVID-19, defined as people with SpO2 ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
The World Health Organization (WHO) recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with COVID-19 (strong recommendation, based on moderate certainty evidence).
The Oxford University RECOVERY Trial issued a press release announcing preliminary results that the drug could reduce deaths by about a third in participants on and by about a fifth in participants on oxygen; it did not benefit people who did not require respiratory support.
In September 2020, the European Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents, from twelve years of age and weighing at least , who require supplemental oxygen therapy.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.
In November 2020, the Public Health Agency of Canada's Clinical Pharmacology Task Group recommended dexamethasone for hospitalized patients requiring mechanical ventilation.
The mechanism of action of dexamethasone involves suppression of late-stage interferon type I programs in severe COVID-19 patients.
Surgery
Dexamethasone is used fairly regularly, often as a single intravenous dose, during surgery to prevent postoperative nausea and vomiting, manage pain, potentially reduce the amount of pain medication required, and help reduce post-surgery hospitalisation time.
Endocrine
Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.
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 adrenocorticotropic hormone (ACTH) production. It is typically given at night.[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]
Pregnancy
Dexamethasone may be given to women at risk of delivering prematurely to promote maturation of the fetus's lungs. This administration, given from one day to one week before delivery, has been associated with low birth weight, although not with increased rates of neonatal death.
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 Intersex. 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 fetuses of women treated are at risk of the condition, and serious adverse events have been documented.
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.
High-altitude illnesses
Dexamethasone is used in the treatment of high-altitude cerebral edema (HACE), as well as high-altitude pulmonary edema (HAPE).
Nausea and vomiting
Intravenous dexamethasone is effective for the 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.
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.
Sore throat
A single dose of dexamethasone or another steroid speeds the improvement of a sore throat.
Contraindications
of dexamethasone include,[ but are not limited to:
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Adverse effects
The exact incidence of the adverse effects of dexamethasone is 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.[ (Accept terms and conditions to open PDF, which doesn't work in archived version)][ (Accept terms and conditions to open PDF, which doesn't work in archived version)]
Common
Unknown frequency
Withdrawal
Sudden withdrawal after long-term treatment with corticosteroids can lead to[
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Interactions
Known drug interactions include:[
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Inducers of hepatic microsomal enzymes such as barbiturates, phenytoin, and rifampicin can reduce the half-life of dexamethasone.
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Cotreatment with oral contraceptives can increase its volume of distribution.
Pharmacology
Pharmacodynamics
As a glucocorticoid, dexamethasone is an agonist of the glucocorticoid receptor (GR).
The activation of the GR by dexamethasone results in dose dependence suppression of the hypothalamic–pituitary–adrenal axis (HPA axis) and of production of endogenous corticosteroids by the , thereby reducing circulating endogenous concentrations of corticosteroids like cortisol and corticosterone.
Dexamethasone poorly penetrates the blood–brain barrier into the central nervous system due to binding to P-glycoprotein.
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.
Synthesis
To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative.
Spectroscopy
In chemistry, spectroscopy is used to analyze products of reactions. To understand if dexamethasone is synthesized from a reaction, spectroscopy must be taken and compared to the literature spectrum. There are multiple spectroscopy analyses that can be taken including 1H NMR, 13C NMR, IR, Mass spectrometry, and UV/vis spectroscopy.
File:1H NMR for Dexamethasone.png|'''1H NMR for Dexamethasone [
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File:13C NMR for Dexamethasone.png| 13C NMR for Dexamethasone The NMR spectrum shown above can be used to compare to product synthesized through reactions to figure out if Dexamethasone was synthesized. 1H NMR, among other things, shows that there are 29 hydrogens and 13C NMR shows that there are 22 carbons.
File:Infrared spectroscopy of Dexamethasone.png| Infrared spectroscopy of Dexamethasone [Shing, C. (2023). Novel cocrystals of dexamethasone. Hong Kong:]
File:UV-vis spectroscopy of Dexamethasone.png| UV-vis spectroscopy of Dexamethasone [Takegami, S., Kitamura, K., Funakoshi, T., & Kitade, T. (2008). Partitioning of anti-inflammatory steroid drugs into phosphatidylcholine and phosphatidylcholine-cholesterol small unilamellar vesicles as studied by second-derivative spectrophotometry. Chemical and Pharmaceutical Bulletin, 56(5), 663–667. ]
Using IR spectroscopy, the peaks show the functional groups found in the molecule. You can see peaks at 3472, 1662, and 1618 representing alcohol, aldehyde, and alkene functional groups. UV-vis spectroscopy is another way to analyze a product to figure out what it is.
Finally, mass spectroscopy showed peaks at: 393.1, 355.2 147.1 m/z. The peak at 393.1 m/z is the peak for dexamethasone as its molecular weight is 392.46 m/z.[Mulabagal, V., Wilson, C., & Hayworth, J. S. (2017). An ultrahigh-performance chromatography/tandem mass spectrometry quantitative method for trace analysis of potential endocrine disrupting steroid hormones in estuarine sediments. Rapid Communications in Mass Spectrometry, 31(5), 419–429. ]
History
Dexamethasone was first synthesized by Philip Showalter Hench in 1957.
On 16 June 2020, the RECOVERY Trial announced preliminary results stating that dexamethasone improves survival rates of hospitalized patients with COVID-19 receiving oxygen or on a ventilator. Benefits were only observed in patients requiring respiratory support; those who did not require breathing support saw a worse survival rate than the control group, although the difference may have been due to chance.
The World Health Organization (WHO) states that dexamethasone should be reserved for seriously ill and critical patients receiving COVID-19 treatment in a hospital setting,
In July 2020, the European Medicines Agency (EMA) started reviewing results from the RECOVERY study arm that involved the use of dexamethasone in the treatment of patients with COVID-19 admitted to the hospital to provide an opinion on the results and in particular the potential use of dexamethasone for the treatment of adults with COVID-19.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
Society and culture
Price
Dexamethasone is inexpensive.[ In India, a course of treatment for preterm labor is about .][ The drug is available in most areas of the world.][
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Nonmedical use
Dexamethasone is given to prostituted Bangladeshi children, causing weight gain aimed at making them appear older and healthier to customers and police.
Dexamethasone and most are banned by sporting bodies including the World Anti-Doping Agency.
Veterinary use
Combined with marbofloxacin CAS number 115550-35-1and clotrimazole, dexamethasone is available under the name Aurizon, CAS number 50-02-2, 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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