What is the mechanism of action of dexamethasone?

From the Guidelines

Dexamethasone is a synthetic glucocorticoid that works by binding to glucocorticoid receptors in the cytoplasm of cells, forming a complex that moves into the nucleus where it regulates gene expression, leading to anti-inflammatory and immunosuppressive effects. This mechanism of action is supported by various studies, including those on its use in bacterial meningitis 1, acute lymphoblastic leukemia 1, and chemotherapy-induced nausea and vomiting 1. The drug's ability to reduce inflammation by inhibiting the production of inflammatory mediators, decreasing the release of cytokines, and preventing the migration of inflammatory cells to sites of inflammation makes it effective in treating various conditions. Additionally, dexamethasone affects metabolism by promoting gluconeogenesis in the liver, which increases blood glucose levels.

Some key points about dexamethasone's mechanism of action and effects include:

• It has a long biological half-life of 36-54 hours, making it suitable for once-daily dosing.
• Dexamethasone is approximately 25-30 times more potent than hydrocortisone and has minimal mineralocorticoid activity, which means it causes less fluid retention and electrolyte disturbances compared to some other corticosteroids.
• The use of dexamethasone has been studied in various contexts, including its role in reducing cerebral edema and managing certain types of shock, as well as its efficacy in preventing postoperative nausea and vomiting (PONV) 1.
• A recent meta-analysis with 6696 patients showed that a 4–5 mg dose of dexamethasone had clinical effects similar to the 8–10 mg dose in preventing PONV 1.

Overall, the mechanism of action of dexamethasone involves its binding to glucocorticoid receptors, leading to anti-inflammatory and immunosuppressive effects, making it a valuable drug in the treatment of various inflammatory and autoimmune conditions.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Dexamethasone sodium phosphate has a rapid onset but short duration of action when compared with less soluble preparations. Because of this, it is suitable for the treatment of acute disorders responsive to adrenocortical steroid therapy Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs, including dexamethasone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects In addition, they modify the body’s immune responses to diverse stimuli. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone.

The mechanism of action of dexamethasone involves its potent anti-inflammatory effects, as well as its ability to cause metabolic effects and modify the body's immune responses. The key aspects of its mechanism of action include:

• Anti-inflammatory effects: used to treat disorders of many organ systems
• Metabolic effects: causes profound and varied effects
• Immune responses: modifies the body's response to diverse stimuli 2

From the Research

Mechanism of Action of Dexamethasone

The mechanism of action of dexamethasone involves several key processes:

• Suppression of cytokine production and induction of apoptosis in inflammatory cells 3
• Modulation of the activity of ion channels to regulate electrolyte and water transport across the airway epithelium, reducing airway surface liquid volume 4
• Up-regulation of inflammatory pathways in human hippocampal cells, potentially contributing to the pathogenesis of depression 5
• T cell receptor-independent immunosuppression, involving the inhibition of early cytokine-signalling events 6
• Modulation of the expression of the murine TCR zeta gene locus, leading to an increase in TCR zeta protein 7

Key Effects of Dexamethasone

Some of the key effects of dexamethasone include:

• Suppression of type 2 inflammation and mediation of apoptosis in Th2 cells 3
• Reduction of airway surface liquid volume, potentially reversing airway flooding in conditions such as COVID-19 4
• Potentiation of inflammatory effects in human hippocampal cells, potentially contributing to the pathogenesis of depression 5
• Inhibition of T cell proliferation and activation, independent of T cell receptor stimulation 6
• Up-regulation of TCR zeta gene locus transcription, leading to an increase in TCR zeta protein 7

Therapeutic Implications

The therapeutic implications of dexamethasone's mechanism of action include:

• Effective treatment of asthma exacerbations and other inflammatory conditions 3
• Potential treatment of COVID-19, particularly in severe cases with hyperactive immune response 4
• Possible role in the treatment of depression, although further research is needed to fully understand the implications of dexamethasone's effects on human hippocampal cells 5
• Immunomodulating activity, potentially contributing to its therapeutic effects in a range of conditions 6, 7