Introduction
Dexamethasone is a potent, long-acting synthetic glucocorticoid with approximately 25 times the anti-inflammatory potency of hydrocortisone. As a corticosteroid, it exerts profound effects on various body systems including immune function, inflammation, carbohydrate metabolism, and electrolyte balance. First synthesized in 1957, dexamethasone has become a cornerstone therapy in numerous clinical conditions ranging from inflammatory disorders to oncological emergencies.
Mechanism of Action
Dexamethasone exerts its effects primarily through genomic mechanisms. It diffuses across cell membranes and binds to intracellular glucocorticoid receptors, forming a complex that translocates to the nucleus. This complex binds to glucocorticoid response elements (GREs) in DNA, modulating gene transcription. The drug increases synthesis of anti-inflammatory proteins (lipocortin-1) while decreasing production of pro-inflammatory mediators (cytokines, chemokines, adhesion molecules, inflammatory enzymes). Additionally, dexamethasone promotes apoptosis of lymphocytes and eosinophils while inhibiting neutrophil apoptosis. Its non-genomic effects include membrane stabilization and inhibition of phospholipase A2 activity.
Indications
FDA-Approved Indications:- Inflammatory and autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus)
- Allergic conditions (severe allergic reactions, angioedema)
- Dermatological diseases (pemphigus, severe psoriasis)
- Hematologic disorders (immune thrombocytopenia, autoimmune hemolytic anemia)
- Endocrine disorders (congenital adrenal hyperplasia, adrenal insufficiency)
- Cerebral edema
- Nausea and vomiting associated with chemotherapy
- Diagnostic testing (Cushing's syndrome)
- COVID-19 respiratory complications (in hospitalized patients requiring oxygen)
- Acute spinal cord injury
- Thyroid eye disease
- Prevention of acute mountain sickness
- Antenatal corticosteroid therapy for fetal lung maturation
Dosage and Administration
General Dosing:- Oral: 0.75-9 mg daily in divided doses (equivalent to 5-60 mg prednisone)
- IV/IM: 0.5-9 mg daily (dose varies by indication)
- Topical: Apply thin film to affected area 1-4 times daily
- Cerebral edema: Initial 10 mg IV followed by 4 mg IM/IV every 6 hours
- Anti-emetic: 10-20 mg IV 15-30 minutes before chemotherapy
- Inflammatory conditions: 0.75-9 mg daily in divided doses
- Adrenal insufficiency: 0.75-0.9 mg daily
- Hepatic impairment: Dose reduction may be necessary
- Renal impairment: No significant adjustment needed
- Elderly: Lower doses recommended due to increased sensitivity
- Pediatrics: Dose based on severity rather than strict weight-based calculations
Pharmacokinetics
Absorption: Well absorbed from GI tract (bioavailability 80-90%) Distribution: Widely distributed throughout body tissues, crosses placenta, appears in breast milk. Protein binding: 70% Metabolism: Hepatic via CYP3A4 to inactive metabolites Elimination: Primarily renal (65%), fecal elimination (15%). Half-life: 36-54 hours Onset of Action: Several hours to days for anti-inflammatory effectsContraindications
- Systemic fungal infections
- Known hypersensitivity to dexamethasone or components
- Live virus vaccinations during immunosuppressive therapy
- Active untreated infections (unless concurrent anti-infective therapy)
- Idiopathic thrombocytopenic purpura (IM route)
Warnings and Precautions
Black Box Warnings:- Corticosteroids can cause serious and fatal infections due to immunosuppression
- Avoid use in patients with known or suspected strongyloides infection (risk of hyperinfection)
- Adrenal suppression with prolonged use (>2 weeks)
- Increased intraocular pressure and cataract formation
- Psychiatric effects including euphoria, insomnia, mood swings, depression
- Glucose intolerance and worsening of diabetes mellitus
- Osteoporosis and increased fracture risk
- Growth suppression in children
- Cardiovascular risk including hypertension and fluid retention
- Gastrointestinal perforation risk in patients with GI disorders
- Kaposi's sarcoma reported with corticosteroid therapy
Drug Interactions
Significant Interactions:- Anticoagulants: Altered anticoagulant effect
- Antidiabetic agents: Reduced hypoglycemic effect
- CYP3A4 inducers (phenytoin, rifampin): Reduced dexamethasone efficacy
- CYP3A4 inhibitors (ketoconazole): Increased dexamethasone levels
- Diuretics: Enhanced potassium wasting
- NSAIDs: Increased GI ulcer risk
- Live vaccines: Reduced vaccine efficacy, increased adverse reactions
- Cardiac glycosides: Increased risk of arrhythmias due to hypokalemia
Adverse Effects
Common (≥1%):- Insomnia
- Increased appetite
- Weight gain
- Fluid retention
- Mood changes
- Hyperglycemia
- Indigestion
- Severe infections
- Adrenal insufficiency
- Osteoporosis and fractures
- Avascular necrosis
- Peptic ulcer disease
- Pancreatitis
- Glaucoma
- Psychiatric disorders
- Anaphylaxis
- Thromboembolic events
Monitoring Parameters
Baseline:- Complete blood count
- Electrolytes, glucose, calcium
- Liver and renal function
- Blood pressure
- Weight and height (in children)
- Bone density (if long-term therapy anticipated)
- Ophthalmologic examination
- Blood glucose (regular monitoring)
- Blood pressure (weekly initially)
- Weight (weekly)
- Signs of infection
- Electrolytes (particularly potassium)
- Growth velocity in children
- Bone density (annually if long-term use)
- Ophthalmologic exams (every 6-12 months)
- Signs of adrenal insufficiency
- Disease flare symptoms
- Blood pressure and electrolyte monitoring
Patient Education
Key Points:- Take exactly as prescribed; do not stop abruptly
- Take with food to minimize GI upset
- Report signs of infection (fever, sore throat)
- Monitor blood sugar if diabetic
- Report vision changes or eye pain
- Notify all healthcare providers of dexamethasone use
- Carry medical identification indicating steroid use
- Avoid exposure to infections when possible
- Report unusual weight gain, swelling, or mood changes
- Do not receive live vaccines while taking dexamethasone
- Maintain adequate calcium and vitamin D intake
- Regular weight-bearing exercise to maintain bone health
- Do not double dose if missed
- Take morning doses early to minimize sleep disturbance
- Gradual tapering required after prolonged therapy
- Inform dentist about medication before procedures
References
1. Lexicomp Online. Dexamethasone monograph. Wolters Kluwer Clinical Drug Information. 2. National Institutes of Health. Dexamethasone. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2017. 3. Liu D, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy, Asthma & Clinical Immunology. 2013;9(1):30. 4. RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19. New England Journal of Medicine. 2021;384(8):693-704. 5. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clinical Science. 1998;94(6):557-572. 6. American Society of Health-System Pharmacists. AHFS Drug Information. Bethesda, MD.