Dexamethasone, a potent glucocorticoid with long-acting properties, has etched its mark as one of the most indispensable medications in the realm of neurosurgery. Its journey from a rheumatological remedy to a cornerstone in treating brain tumours showcases the dynamic interplay between medical innovation and therapeutic adaptation.
Dexamethasone, a potent glucocorticoid with long-acting properties, has etched its mark as one of the most indispensable medications in the realm of neurosurgery. Its journey from a rheumatological remedy to a cornerstone in treating brain tumours showcases the dynamic interplay between medical innovation and therapeutic adaptation.
In 1958, Glen E Arth synthesised dexamethasone, a 16-alpha-methylated analogue of cortisone, primarily for managing rheumatoid arthritis. However, it was Joseph Galicich, a resident in neurosurgery at the time, who recognised its potential beyond rheumatology. Galicich administered dexamethasone to patients post-craniotomy for tumour excision, witnessing remarkable improvements in paresis, resolution of midline shift, and reduced mortality rates. His advocacy for clinical trials propelled dexamethasone into the realm of neurosurgical practice, where it swiftly became a staple.
Yet, as the landscape of neuro-oncological therapeutics expands to encompass immunotherapy, the immunosuppressive effects of dexamethasone present a conundrum. How does one manage symptomatic relief without compromising the efficacy of oncological treatments? Despite its enduring presence in medical practice for over six decades, dexamethasone's role in the modern context prompts a re-evaluation, particularly in the face of emerging neuro-oncological paradigms.
Today, dexamethasone is available in various formulations, including intravenous, oral, nasal, ophthalmic, and topical creams, catering to a spectrum of diseases ranging from multiple myeloma to psoriasis. While chronic therapy with glucocorticoids such as dexamethasone is associated with adverse effects like osteoporosis, fluid retention, and hyperglycaemia, their acute efficacy underscores their widespread adoption in medical management.
The mechanism of action of dexamethasone, like other corticosteroids, is multifaceted, targeting multiple drug receptors. Its anti-inflammatory prowess primarily stems from its role as an agonist of ligand-bound glucocorticoid receptors, orchestrating signalling pathways that mitigate inflammation. However, the poly-pharmacology of dexamethasone extends beyond anti-inflammatory effects, encompassing interactions with mineralocorticoid receptors, which contribute to side effects such as salt and water retention.
Since its inception into the market in 1959, dexamethasone has emerged as one of the premier orally bioavailable corticosteroids, alongside prednisone. With a track record spanning over six decades, dexamethasone has exhibited efficacy across a multitude of indications, from rheumatic disorders to severe allergies, asthma, and brain swelling. Its versatility has rendered it a favoured choice among physicians, evident in its ‘off-label’ use in severe Covid-19 cases to alleviate pneumonia symptoms.
The RECOVERY clinical trial, validating dexamethasone's efficacy in severe Covid-19, serves as a testament to the enduring legacy of this medication. As medical practitioners navigate the evolving landscape of therapeutic interventions, dexamethasone stands as a testament to the enduring adaptability and efficacy of pharmacotherapy.
References
Vazquez S, Gold J, Spirollari E, Akmal S, Hanft SJ. The story of dexamethasone and how it became one of the most widely used drugs in neurosurgery. J Neurosurg. 2023 Nov 24;140(4):1191-1197. doi: 10.3171/2023.9.JNS231099. PMID: 38000066.
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