DEXAMETHASONE

Indications

• Suppression of inflammatory and allergic disorders
• Adjunctive treatment of suspected bacterial meningitis
• Reduction of peri- and neonatal morbidity and mortality in preterm birth
• Management of severe croup
• Congenital adrenal hyperplasia
• COVID-19 requiring supplemental oxygen

Dosage

Adults: For adults, the typical dosing varies by condition

Mechanism of action

Dexamethasone binds to the glucocorticoid receptor, leading to changes in gene expression that result in decreased inflammatory and immune responses. It inhibits phospholipase A2, reducing the formation of pro-inflammatory mediators, and promotes anti-inflammatory genes like interleukin-10. The drug also inhibits neutrophil apoptosis and demargination, contributing to its anti-inflammatory effects. Its glucocorticoid activity results in significant immunosuppression at higher doses.

Pharmacodynamics

Dexamethasone's pharmacodynamics involve the modulation of inflammatory responses through glucocorticoid receptor binding. It inhibits pro-inflammatory signals while promoting anti-inflammatory signals. The duration of action varies based on the administration route, and careful dosing is required to avoid suppression of the hypothalamic-pituitary-adrenal axis and increased infection risk. The drug has a wide therapeutic window, allowing for higher doses than the body's natural production.

Pharmacokinetics

Dexamethasone is well-absorbed after oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It is extensively metabolized in the liver, primarily through hepatic cytochrome P450 enzymes. The elimination half-life ranges from 3 to 4 hours, although it may be longer in certain populations. The drug is excreted mainly in urine as metabolites. The pharmacokinetics can be affected by factors such as liver function and co-administered medications.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to dexamethasone or any component of the formulation
• Active tuberculosis
• Cautious use in patients with peptic ulcer disease

Adverse effects

• Oedema
• Hypotension
• Increased susceptibility to infections
• Mood changes
• Cushing's syndrome
• Hyperglycemia
• Gastrointestinal perforation
• Osteoporosis
• Adrenal suppression

Interactions

• Severe interaction with avapritinib (decreases exposure)
• Moderate interaction with mitotane (decreases exposure)
• Moderate interaction with monoclonal antibodies (decreases exposure)
• Moderate interaction with tocilizumab (decreases exposure)
• Moderate interaction with aprepitant (increases exposure)
• Moderate interaction with netupitant (increases exposure)
• Moderate interaction with rifampicin (decreases exposure)
• Unknown interaction with cobicistat (increases exposure)
• Unknown interaction with caspofungin (decreases concentration)
• Unknown interaction with idelalisib (increases exposure)

Precautions

• Use with caution in patients with a history of tuberculosis
• Monitor for signs of infection due to immunosuppressive effects
• Consider dose adjustments in hepatic impairment
• Taper dosage to avoid withdrawal symptoms after prolonged use
• Monitor blood glucose levels in diabetic patients

Pregnancy

Dexamethasone is classified as a pregnancy category C drug. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dexamethasone is excreted in breast milk. Caution is advised when administering to breastfeeding women, and the risks versus benefits should be considered.

Storage

Store at room temperature (15-30 degrees Celsius), protect from light, and keep out of reach of children.

Formulations

• Tablet (6 mg)
• Solution for injection (3.3 mg/1 ml)
• Dexamethasone sodium phosphate solution for injection (6.6 mg/2 ml)

Indications

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

Mechanism of action

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels. Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA, and stimulate transcription of mRNA and subsequent protein synthesis of enzymes ultimately responsible for anti-inflammatory effects of topical application of corticosteroids to the eye. In high concentrations which may be achieved after topical application, corticosteroids may exert direct membrane effects. Corticosteroids decrease cellular and fibrinous exudation and tissue infiltration, inhibit fibroblastic and collagen-forming activity, retard epithelial regeneration, diminish postinflammatory neovascularization and reduce toward normal levels the excessive permeability of inflamed capillaries. /Corticosteroids (Otic)/ Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/ Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocttes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids. The overall actions of topical corticosteroids are catabolic. /Corticosteroids (topical)/

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Dexamethasone's duration of action varies depending on the route. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.