Dexamethasone

Dexamethasone is a potent synthetic glucocorticoid with anti-inflammatory, immunosuppressive, and antiemetic properties. It is widely used in various medical conditions, including autoimmune diseases, allergies, cerebral edema, and as an adjunct in cancer therapy.

Uses

• Anti-inflammatory and Immunosuppressive: Management of conditions such as asthma, COPD exacerbations, rheumatoid arthritis, and inflammatory bowel disease.
• Cerebral Edema: Reduces intracranial pressure in brain tumors or cerebral edema.
• Allergic Reactions: Treatment of severe allergic reactions, including anaphylaxis.
• Adjunct in Cancer Therapy: Used as an antiemetic and to reduce inflammation during chemotherapy.
• Adrenal Insufficiency: Replacement therapy in primary or secondary adrenal insufficiency.
• COVID-19: Reduces the inflammatory response in severe cases.
• Postoperative Nausea and Vomiting (PONV): Used perioperatively to prevent PONV.
• Preterm Labor: Accelerates fetal lung maturation in cases of threatened preterm labor.
• Croup: Reduces airway inflammation in laryngotracheobronchitis.
• Perioperative Stress Dose: Administered to patients on long-term steroid therapy to prevent adrenal crisis during surgery.

Dosage and Administration

Adults

• Inflammatory and Allergic Conditions: 0.5-10 mg/day, typically given once daily or divided into 2-4 doses depending on severity.
• Cerebral Edema: 10 mg IV initially, then 4 mg every 6 hours.
• COVID-19: 6 mg IV or oral once daily for 10 days.
• Preterm Labor: 6 mg IM every 12 hours for 4 doses.

Pediatrics

• Inflammatory and Allergic Conditions: 0.08-0.3 mg/kg/day (max 16 mg/day), divided into 1-2 doses.
• Croup: 0.15-0.6 mg/kg as a single dose (commonly 0.6 mg/kg).

Dose Adjustments in Specific Diseases

• Hepatic Impairment: Dose adjustments may be required due to altered metabolism.
• Renal Impairment: No specific dose adjustment required.
• Elderly: Consider lower doses due to increased risk of osteoporosis and fractures.

Drug Combinations in Use

• With NSAIDs: Monitor for gastrointestinal ulcers.
• With Diuretics: Monitor potassium levels to prevent hypokalemia.
• With Insulin or Oral Hypoglycemics: Increased insulin needs may arise.
• With Anticoagulants: Monitor INR levels closely due to potential interactions with warfarin.

Presentation or Form

• Tablets: 0.5 mg, 1 mg, 4 mg, 6 mg.
• Injection: 4 mg/mL, 10 mg/mL.
• Oral Solution: 1 mg/mL.
• Ophthalmic Solution: 0.1% (for treating eye conditions).

Pharmacokinetics

• Absorption: Well absorbed orally.
• Onset: 1-2 hours (oral), immediate (IV).
• Distribution: Widely distributed, crosses the placenta, and is present in breast milk.
• Metabolism: Hepatic, primarily by CYP3A4.
• Excretion: Renal excretion of metabolites.
• Half-life: 36-54 hours (long-acting).

Pharmacodynamics

Dexamethasone acts by binding to intracellular glucocorticoid receptors, modulating gene expression to inhibit pro-inflammatory cytokines and immune responses.

Drug Interactions

• NSAIDs: Increased risk of gastrointestinal ulcers and bleeding.
• Diuretics: Potential risk of hypokalemia.
• Anticoagulants: May alter warfarin effects.
• Antifungals (e.g., Ketoconazole): Can inhibit dexamethasone metabolism.
• Rifampin and Phenytoin: Increase dexamethasone clearance.

Comparison with Other Drugs in the Same Category

Drug	Potency	Duration of Action	Mineralocorticoid Activity	Common Use
Dexamethasone	High	36-54 hours	Minimal	Severe inflammation
Hydrocortisone	Low	8-12 hours	Moderate	Adrenal insufficiency
Prednisone	Moderate	18-36 hours	Low	Autoimmune diseases
Methylprednisolone	High	30-36 hours	Minimal	Acute inflammation

Precautions and Special Considerations

• Elderly: Monitor bone density; consider calcium and vitamin D supplementation.
• Hepatic Impairment: Dose adjustment may be needed.
• Pregnancy and Lactation: Category C. Use cautiously, especially in early pregnancy. Excreted in breast milk.
• Tapering: Gradual dose reduction is necessary to avoid adrenal insufficiency.
• Infections: Avoid use in uncontrolled infections unless life-saving.

Side Effects

• Common: Hyperglycemia, weight gain, fluid retention, insomnia, mood changes, gastrointestinal upset.
• Serious: Adrenal suppression, osteoporosis, increased infection risk, Cushing’s syndrome, peptic ulcers.

Recent Updates and Guidelines

• COVID-19: Recent studies have reinforced dexamethasone’s role in managing severe COVID-19 cases by reducing mortality rates in ventilated patients.
• WHO Guidelines: Recommends dexamethasone for severe COVID-19 pneumonia.

Facts to Remember

• Potency: 25 times more potent than hydrocortisone and 5 times more potent than prednisone.
• Administration: Can be given orally, intravenously, intramuscularly, and topically.
• Tapering Requirement: Essential after long-term use.

References

• NCBI StatPearls - Dexamethasone: https://www.ncbi.nlm.nih.gov/books/NBK482130/
• Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th edition.
• Stoelting’s Pharmacology and Physiology in Anesthetic Practice, 5th edition.
• WHO Guidelines on Corticosteroid Use in COVID-19.