Clinical Use of Dexamethasone

Hollander, Joseph Lee

doi:10.1001/jama.1960.03020040004002

Cited by 31 publications

(8 citation statements)

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“…Dex reduced deaths by approximately 33% in patients requiring ventilation and by 20% in those requiring oxygen (Healthcare, 2020). Studies show that Dex has been used to reduce inflammation in a wide range of conditions, including inflammatory disorders and certain cancers (Hollander, 1960;Stoll, 1960). The WHO has added this compound on the Model List of Essential Medicines since 1977 in multiple formulations, and is currently off-patent and commonly available in most countries (Organization WH, 1977;Villar et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Computational insight of dexamethasone against potential targets of SARS-CoV-2

Fadaka

Sibuyi

Madiehe

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The health sector has been on the race to find a potent therapy for coronavirus disease (COVID)-19, a diseases caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. Repurposed anti-viral drugs have played a huge role in combating the virus, and most recently, dexamethasone (Dex) have shown its therapeutic activity in severe cases of COVID-19 patients. The study sought to provide insights on the anti-COVID-19 mechanism of Dex at both atomic and molecular level against SARS-CoV-2 targets. Computational methods were employed to predict the binding affinity of Dex to SARS-CoV-2 using the Schrodinger suite (v2020-2). The target molecules and ligand (Dex) were retrieved from PDB and PubChem, respectively. The selected targets were SARS-CoV-2 main protease (Mpro), and host secreted molecules glucocorticoid receptor, and Interleukin-6 (IL-6). Critical analyses such as Protein and ligand preparation, molecular docking, molecular dynamic (MD) simulations, and absorption, distribution, metabolism, excretion (ADME), and toxicity analyses were performed using the targets and the ligand as inputs. Dex showed stronger affinity to its theoretical (glucocorticoid) receptor with a superior docking score of À14.7 and a good binding energy value of À147.48 kcal/mol; while short hydrogen bond distances were observed in both Mpro and IL-6 when compared to glucocorticoid receptor. Based on these findings, Dex-target complexes were used to perform MD simulations to analyze Dex stability at 50 ns. This study demonstrates that Dex could bind to both the viral and host receptors as a potential drug candidate for COVID-19. To ascertain the biological fitness of this study, other SARS-CoV-2 targets should be explored. Also, the in vitro studies of dexamethasone against several SARS-CoV-2 targets warrant further investigation.

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Section: Introductionmentioning

confidence: 99%

Computational insight of dexamethasone against potential targets of SARS-CoV-2

Fadaka

Sibuyi

Madiehe

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…Dexamethasone is a potent anti-inflammatory drug that belongs to the category of synthetic adrenal corticosteroid [ 3 ]. Compared with other glucocorticoids, such as hydrocortisone and prednisone, dexamethasone is highly potent.…”

Section: Dexamethasone: a Synthetic Corticosteroidmentioning

confidence: 99%

“…Dexamethasone has been in use since the 1960s and was listed in the WHO Model List of Essential Medicines in 1977 [ 3–5 ]. The steroid drug dexamethasone is made synthetically and, like other corticoids, affects the immune system.…”

Section: Introductionmentioning

confidence: 99%

“…Dexamethasone has been widely used in conditions with inflammation. These include systemic lupus, rheumatoid arthritis, acute gouty arthritis, ulcerative colitis, psoriatic arthritis and Crohn’s disease [ 3 , 6 ]. Dexamethasone is also used in allergic conditions such as allergic rhinitis, bronchial asthma, contact and atopic dermatitis and drug-induced dermatitis when patients fail to respond other treatments [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacogenomic Considerations for Repurposing of Dexamethasone as a Potential Drug Against SARS-CoV-2 Infection

et al. 2021

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Immunomodulatory and analgesic effects of dexamethasone are clinically well established, and this synthetic corticosteroid acts as an agonist of glucocorticoid receptors. Early results of the RECOVERY Trial from the United Kingdom and others suggest certain benefits of dexamethasone against COVID-19 chronic patients. The efforts have been acknowledged by World Health Organization with an interim guideline to use in patients with a severe and critical illness. The inherent genetic variations in genes such as CYP3A5, NR3C1, NR3C2, etc., involved in the pharmacokinetic and pharmacodynamic processes may influence dexamethasone’s effects as an anti-inflammatory drug. Besides, the drug may influence transcriptome or metabolic changes in the individuals. In the present review, we summarize the reported genetic variations that impact dexamethasone response and discuss dexamethasone-induced changes in transcriptome and metabolome that may influence potential treatment outcome against COVID-19.

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“…Dagegen findet sich bei den mit Fluorhydrocortison be- Prednisolon beträgt sie etwa das 0,8fache. Triamcinolonacetonid besitzt nach diesen Autoren keine, nach anderen Untersuchern eine nur geringe mineralotrope Wirkung (Hollander, 1960;Grabner, 1972 Meredig und Mitarb. (1980)…”

Section: Ergebnisseunclassified

Der Einfluß lokal applizierter Kortikosteroide auf den Mineralhaushalt*

Eckardt¹

1984

Klin Monatsbl Augenheilkd

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The author performed a prospective study to test the mineralocorticoid activity of high doses of topically applied corticosteroids. Eight patients were treated with prednisolone eye drops. Twelve patients received fluorhydrocortisone, 9 patients triamcinolone acetonide and 11 dexamethasone; subconjunctival or parabulbar injections were used in all cases. Only the patients treated with fluorhydrocortisone showed a mineralocorticoid effect, i.e., reduced sodium excretion and a high potassium waste in the urine together with a decrease in serum potassium. Fluorhydrocortisone must not be applied topically because the risk of hypokalemia involved is so great.

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Clinical Use of Dexamethasone

Cited by 31 publications

References 8 publications

Computational insight of dexamethasone against potential targets of SARS-CoV-2

Computational insight of dexamethasone against potential targets of SARS-CoV-2

Pharmacogenomic Considerations for Repurposing of Dexamethasone as a Potential Drug Against SARS-CoV-2 Infection

Der Einfluß lokal applizierter Kortikosteroide auf den Mineralhaushalt*

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