DEXAMED 0.1%W/V EYE/EAR DROPS

Indications

• Autoimmune disorders
• Inflammatory conditions
• Asthma exacerbations
• Allergic reactions
• Certain cancers (e.g., multiple myeloma, lymphoma)
• Cerebral edema
• Severe COVID-19

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on condition and age.

Adults: Refer to BNF for specific dosing recommendations based on condition and severity.

Mechanism of action

Dexamethasone operates primarily by binding to the glucocorticoid receptor, leading to altered gene expression. This results in decreased vasodilation and capillary permeability, as well as reduced leukocyte migration to sites of inflammation. The drug inhibits the action of phospholipase A2, thereby decreasing the production of arachidonic acid derivatives. Additionally, it suppresses the activity of inflammatory transcription factors like NF-Kappa B, while promoting the expression of anti-inflammatory genes, such as interleukin-10. At higher doses, dexamethasone can exert immunosuppressive effects and affect mineralocorticoid receptors, influencing sodium and potassium levels.

Pharmacodynamics

Dexamethasone binds to glucocorticoid receptors, inhibiting pro-inflammatory signals and enhancing anti-inflammatory actions. The duration of its effects can vary based on the administration route. It possesses a wide therapeutic window, allowing for significant dose flexibility. However, long-term use may lead to hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Pharmacokinetics

Dexamethasone is well absorbed following oral administration and has a long half-life, allowing for once-daily dosing in many cases. It is extensively metabolized in the liver, with a high volume of distribution. The elimination half-life can range from 3 to 4 hours, depending on the route of administration. The drug is primarily excreted as metabolites in urine.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to dexamethasone or any component of the formulation
• Live vaccines (in immunosuppressed patients)

Adverse effects

• Increased risk of infections
• Hyperglycemia
• Hypertension
• Fluid retention
• Gastrointestinal perforation
• Osteoporosis
• Psychiatric effects (e.g., mood changes, depression)
• Cushing's syndrome
• Adrenal suppression

Interactions

• Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal adverse effects
• Anticoagulants (e.g., warfarin) may have altered effects
• Live vaccines may be less effective or cause disease in immunocompromised patients
• CYP3A4 inhibitors and inducers affect dexamethasone metabolism

Precautions

• Caution in patients with a history of peptic ulcer disease
• Monitor for signs of infection during therapy
• Gradual withdrawal is recommended to avoid adrenal insufficiency after prolonged use
• Use with caution in diabetic patients due to potential for hyperglycemia

Pregnancy

Dexamethasone is classified as category C. Risk cannot be ruled out; use only if clearly needed.

Breast-feeding

Dexamethasone is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets (e.g., 0.5 mg, 1 mg, 2 mg, 4 mg)
• Injection (e.g., 4 mg/mL, 10 mg/mL)
• Topical formulations (e.g., creams, ointments)

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.