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Dexamethasone is a fluorinated glucocorticoid medication<ref name=AHFS2015/> used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye surgery, superior vena cava syndrome (a complication of some forms of cancer),<ref>Template:Cite book</ref> and along with antibiotics in tuberculosis.<ref name=AHFS2015/> In adrenocortical insufficiency, it may be used in combination with a mineralocorticoid medication such as fludrocortisone.<ref name=AHFS2015/> In preterm labor, it may be used to improve outcomes in the baby.<ref name=AHFS2015/> It may be given by mouth, as an injection into a muscle, as an injection into a vein, as a topical cream or ointment for the skin or as a topical ophthalmic solution to the eye.<ref name=AHFS2015/> The effects of dexamethasone are frequently seen within a day and last for about three days.<ref name=AHFS2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The long-term use of dexamethasone may result in thrush, bone loss, cataracts, easy bruising, or muscle weakness.<ref name=AHFS2015/> 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.<ref name="Drugs.com pregnancy">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In Australia, the oral use is category A, meaning it has been frequently used in pregnancy and not been found to cause problems to the baby.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It should not be taken when breastfeeding.<ref name=AHFS2015/> Dexamethasone has anti-inflammatory and immunosuppressant effects.<ref name=AHFS2015/>

Dexamethasone was first synthesized in 1957 by Philip Showalter Hench and was approved for medical use in 1958.<ref name="FDA Approval">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="RankovicHargreaves2012">Template:Cite book</ref><ref name=Fis2006>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO22nd">Template:Cite book</ref> In 2022, it was the 234th most commonly prescribed medication in the United States, with more than 1Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is available as a generic medication.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2022, the combination of dexamethasone with neomycin and polymyxin B was the 274th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical usesEdit

File:Dexamethasone.jpg
Dexamethasone phosphate injection ampoules

Anti-inflammatoryEdit

File:Dexamethasone tablets.jpg
Dexamethasone tablets

Dexamethasone is used to treat many inflammatory and autoimmune disorders, such as rheumatoid arthritis and bronchospasm.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref name="pmid19846889">Template:Cite journal</ref>

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.<ref name="pmid8491244">Template:Cite journal</ref>

Dexamethasone is commonly given as a treatment for croup in children.<ref name=":3" /> A single dose can reduce the swelling of the airway to improve breathing and reduce discomfort.<ref name=":3">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref>Template:Cite journal</ref>

It may be useful to counteract allergic anaphylactic shock, however this is not usually recommended by clinical guidelines.<ref>Template:Cite journal</ref>

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 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.<ref>Template:Cite journal</ref> Dexamethasone has also been used with antibiotics to treat acute endophthalmitis.<ref>Template:Cite journal</ref>

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.Template:Medcn

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.<ref>Template:Cite journal</ref>

File:Dexamethasone phosphate for injection.jpg
A single ampoule of dexamethasone phosphate for injection

CancerEdit

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.<ref name="PMID10824073">Template:Cite journal</ref> 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.<ref name="PMID12437261">Template:Cite journal</ref>

In brain tumors (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures.<ref>Template:Cite journal</ref> It is also given in cord compression, where a tumor is compressing the spinal cord.Template:Medcn Evidence on the safety and efficacy of using dexamethasone to treat malignant brain tumors is not clear.<ref name="pmid31346902">Template:Cite journal</ref>

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),<ref name="pmid17043025">Template:Cite journal Template:Free access</ref> or a combination of doxorubicin (Adriamycin) and vincristine or bortezomib/lenalidomide/dexamethasone.Template:Medcn

COVID-19Edit

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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 supplemental oxygen (without ventilation).<ref name=":0">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=":1">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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).<ref name="IDSA">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The IDSA recommends against the use of glucocorticoids for those with COVID-19 without hypoxemia requiring supplemental oxygen.<ref name="IDSA" />

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).<ref name="WHO guidance" /> The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence).<ref name="WHO guidance" />

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 ventilators and by about a fifth in participants on oxygen; it did not benefit people who did not require respiratory support.<ref name="oxford news">Template:Cite news</ref> A meta-analysis of seven clinical trials of critically ill COVID-19 participants, each treated with one of three different corticosteroids found a statistically significant reduction in death.<ref name="Sterne 2020"/> The largest reduction was obtained with dexamethasone (36% compared to placebo).<ref name="Sterne 2020">Template:Cite journal</ref><ref>Template:Cite journal</ref>

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 Template:Convert, who require supplemental oxygen therapy.<ref name="EMA PR">Template:Cite press release Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.<ref name="EMA PR" />

In November 2020, the Public Health Agency of Canada's Clinical Pharmacology Task Group recommended dexamethasone for hospitalized patients requiring mechanical ventilation.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Although dexamethasone, and other glucocorticoids, reduce mortality in COVID-19 they have also been associated with an increased risk of secondary infections,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> secondary infections being a significant issue in critically ill COVID-19 patients.<ref>Template:Cite journal</ref>

The mechanism of action of dexamethasone involves suppression of late-stage interferon type I programs in severe COVID-19 patients.<ref>Template:Cite journal</ref>

SurgeryEdit

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.<ref name=":2" /> The adverse effects of taking steroids after surgery on wound healing, blood sugar levels, and in diabetics are not completely understood; however, dexamethasone likely does not increase the risk of postoperative infections.<ref name=":2">Template:Cite journal</ref>

EndocrineEdit

Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.<ref name="pmid8239231">Template:Cite journal</ref><ref name="pmid18319312">Template:Cite journal</ref>

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

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.<ref>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</ref>

PregnancyEdit

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.<ref name="pmid11275014">Template:Cite journal</ref>

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 fetuses of women treated are at risk of the condition, and serious adverse events have been documented.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Experimental use of dexamethasone in pregnancy for fetal CAH treatment was discontinued in Sweden when one in five cases had adverse events.<ref>Template:Cite journal</ref>

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.<ref name="Hirvikoski_2007">Template:Cite journal</ref><ref name="pmid21164263">Template:Cite journal</ref>

High-altitude illnessesEdit

Dexamethasone is used in the treatment of high-altitude cerebral edema (HACE), as well as high-altitude pulmonary edema (HAPE).<ref name="pmid29959871">Template:Cite journal</ref> It is commonly carried on mountain-climbing expeditions to help climbers deal with complications of altitude sickness.<ref name=MedicalProblems>Template:Cite book</ref><ref name="pmid17438328">Template:Cite journal</ref>

Nausea and vomitingEdit

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.<ref>Template:Cite journal</ref>

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.<ref name="pmid16670361">Template:Cite journal</ref>

Sore throatEdit

A single dose of dexamethasone or another steroid speeds the improvement of a sore throat.<ref>Template:Cite journal</ref>

ContraindicationsEdit

Contraindications of dexamethasone include,<ref name=MSR>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name = TGAO/> but are not limited to:

Adverse effectsEdit

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.<ref name=TGAO>{{#invoke:citation/CS1|citation |CitationClass=web }} (Accept terms and conditions to open PDF, which doesn't work in archived version)</ref><ref name=TGAI>{{#invoke:citation/CS1|citation |CitationClass=web }} (Accept terms and conditions to open PDF, which doesn't work in archived version)</ref><ref name=DM>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=EMCT>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=EMCI>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

CommonEdit

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Unknown frequencyEdit

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WithdrawalEdit

Sudden withdrawal after long-term treatment with corticosteroids can lead to<ref name = TGAO/>

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InteractionsEdit

Known drug interactions include:<ref name = TGAO/>

PharmacologyEdit

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PharmacodynamicsEdit

As a glucocorticoid, dexamethasone is an agonist of the glucocorticoid receptor (GR).<ref name="pmid17045197">Template:Cite journal</ref> It is highly selective for the GR over the mineralocorticoid receptor (MR),<ref name="pmid27967238">Template:Cite journal</ref> and in relation to this, has minimal mineralocorticoid activity.<ref name="pmid25905379">Template:Cite book</ref><ref name="pmid16178782" /><ref name="pmid23947590">Template:Cite journal</ref> This is in contrast to endogenous corticosteroids like cortisol, which bind to and activate both the GR and the MR.<ref name="pmid27967238" /> Dexamethasone is 25 times more potent than hydrocortisone (cortisol) as a glucocorticoid.<ref name="pmid17045197" /> Its affinity (Ki) for the GR was about 1.2Template:NbspnM in one study.<ref name="pmid17045197" />

The activation of the GR by dexamethasone results in dose-dependent suppression of the hypothalamic–pituitary–adrenal axis (HPA axis) and of production of endogenous corticosteroids by the adrenal glands, thereby reducing circulating endogenous concentrations of corticosteroids like cortisol and corticosterone.<ref name="pmid27967238" />

Dexamethasone poorly penetrates the blood–brain barrier into the central nervous system due to binding to P-glycoprotein.<ref name="pmid27967238" /><ref name="pmid9787252">Template:Cite journal</ref> However, higher doses of dexamethasone override the export capacity of P-glycoprotein and enter the brain to produce central activation of GRs.<ref name="pmid27967238" /> In conjunction with the suppression of endogenous corticosteroids by dexamethasone, this results in skewed ratios of activation of peripheral versus central GRs as well as skewed ratios of activation of GRs versus MRs when compared to non-synthetic corticosteroids.<ref name="pmid27967238" /><ref name="pmid9787252" /> These differences can have significant clinical relevance.<ref name="pmid27967238" /><ref name="pmid9787252" />

ChemistryEdit

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.<ref name="Elks2014">Template:Cite book</ref><ref name="IndexNominum2000">Template:Cite book</ref> The molecular and crystal structure of dexamethasone has been determined by X-ray crystallography.<ref>Template:Cite journal</ref> It is a stereoisomer of betamethasone, the two compounds differing only in the spatial configuration of the methyl group at position 16 (see steroid nomenclature).<ref>Template:Cite journal</ref>

SynthesisEdit

To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.Template:Citation needed

File:Dexamethasone synth.png
Dexamethasone synthesis

SpectroscopyEdit

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.

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.

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.<ref>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. {{#invoke:doi|main}}</ref>

HistoryEdit

Dexamethasone was first synthesized by Philip Showalter Hench in 1957.<ref name="targetcivils">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="RankovicHargreaves2012"/> It was introduced for medical use in 1958.<ref name="pmid16178782">Template:Cite journal</ref>

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.<ref name="gnpi">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A preprint containing the full dataset was published on 22 June 2020, and demand for dexamethasone surged after the publication of the preprint.<ref>Template:Cite journal</ref> The preliminary report was published in The New England Journal of Medicine on 18 July 2020.<ref name="NEJM-17July20">Template:Cite journal</ref> The final report was published in February 2021.<ref>Template:Cite journal</ref>

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,<ref name="Reuters 17Jun20">Template:Cite news</ref> and the WHO Director-General stated that "WHO emphasizes that dexamethasone should only be used for patients with severe or critical disease, under close clinical supervision. There is no evidence this drug works for patients with mild disease or as a preventative measure, and it could cause harm."<ref name="WHO DG 22 June 2020">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In July 2020, the WHO stated they were in the process of updating treatment guidelines to include dexamethasone or other steroids.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19.<ref name="WHO guidance">Template:Cite report</ref><ref>Template:Cite press release</ref>

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.<ref name="EMA review">Template:Cite press release Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>Template:Cite news</ref> In September 2020, the EMA received an application for marketing authorization of dexamethasone for COVID-19.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Society and cultureEdit

PriceEdit

Dexamethasone is inexpensive.<ref name=WHODex>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In the United States a month of medication is typically priced less than Template:US$.<ref name=AHFS2015/> In India, a course of treatment for preterm labor is about Template:US$.<ref name=WHODex/> The drug is available in most areas of the world.<ref name=WHODex/>

Nonmedical useEdit

Dexamethasone is given to prostituted Bangladeshi children, causing weight gain aimed at making them appear older and healthier to customers and police.<ref name="BBC_News_2010-05-30">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Dexamethasone and most glucocorticoids are banned by sporting bodies including the World Anti-Doping Agency.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Veterinary useEdit

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.<ref name="wedgewood">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Dexamethasone is also used for emergency patients with hypoadrenocorticism as the drug does not interfere with adrenocorticotropic hormone stimulation testing.<ref>Template:Cite book</ref>

ReferencesEdit

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External linksEdit

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