Generic Name

Hydrocortisone

Mechanism

• Hydrocortisone is a synthetic glucocorticoid with potent anti‑inflammatory and immunosuppressive properties.
• Binding to cytosolic glucocorticoid receptors (GR) leads to a conformational change, nuclear translocation, and modulation of gene transcription.
• Up‑regulates anti‑inflammatory proteins (e.g., annexin‑1, lipocortin) and down‑regulates pro‑inflammatory mediators (e.g., cytokines, COX‑2, iNOS).
• Inhibits phospholipase A₂, reducing arachidonic acid release and downstream prostaglandin/ leukotriene synthesis.
• Modulates immune cell trafficking, decreases capillary permeability, and suppresses cellular activation (T‑cells, macrophages).

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 80 % (first‑pass metabolism); IV drugs bypass first‑pass.
• Distribution: Widely distributed in body fluids; high binding to corticosteroid‑binding globulin.
• Metabolism: Liver CYP3A4 and CYP2B6 convert to inactive metabolites (prednisolone).
• Elimination: Primarily renal; terminal half‑life ~ 3–4 h (oral), ~ 1–2 h IV.
• Drug interactions: Concomitant CYP3A4 inhibitors (ketoconazole) increase plasma levels; inducers (rifampin) reduce efficacy.

Indications

• Acute and chronic inflammatory disorders: eczema, psoriasis, allergic dermatitis.
• Autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis flare‑ups.
• Endocrine replacement: adrenal insufficiency (Addison’s disease).
• Inhaled therapy: asthma, COPD exacerbations (often in combination inhalers).
• Topical and oral anti‑edema: allergic reactions, dermal edema.
• Adjunct in ocular inflammation: conjunctivitis, uveitis.

Contraindications

• Absolute contraindications: Live‑bacterial or fungal UV‑activated vaccines; known hypersensitivity.
• Relative contraindications:
• Untreated systemic infections.
• Uncontrolled diabetes or hypertension.
• Recent ocular infections in topical formulations.
• Warnings:
• Long‑term use may cause adrenal suppression, osteoporosis, and cataract formation.
• Systemic absorption can provoke hyperglycemia and fluid retention.
• Use with caution in glaucoma patients (topical forms).

Dosing

• Tapering: For systemic therapy, reduce dose by 10–20 % every 2–4 weeks to mitigate withdrawal.
• Rebound: Abrupt cessation may precipitate adrenal crisis; insulin‑prednisone‑fluconazole observation.

Adverse Effects

• Common (≥ 10 %):
• Mucocutaneous hyperpigmentation
• Weight gain & abdominal obesity
• Mood swings, insomnia
• Hyperglycemia, dyslipidemia
• Long‑term skin thinning & striae
• Serious (≤ 1 %):
• Adrenal suppression & secondary adrenal insufficiency
• Osteoporosis & rib fractures
• Severe infection susceptibility
• Elevated intra‑ocular pressure and glaucoma (topical use)
• Hypokalemic alkalosis (systemic).

Monitoring

• Endocrine: Serum cortisol, ACTH (if on chronic therapy).
• Metabolic: Blood glucose, HbA1c, lipid profile.
• Bone health: Dual‑energy X‑ray absorptiometry (DEXA) after >6 months.
• Ocular: Intra‑ocular pressure (topical).
• Kidney function: Serum creatinine & GFR for dosing.
• Side‑effect surveillance: Periodic assessment of skin integrity, signs of infection.

Clinical Pearls

• Adrenal suppression alert: Even a 3‑day burst can blunt the hypothalamic‑pituitary‑adrenal (HPA) axis; perform a rapid‑ACTH test before chronic use.
• “Oral Budesonide” is first‑line inhaled CBT for asthma; Hydrocortisone** remains the standard rescue for acute severe asthma when rapid systemic control is needed.
• Topical high‑potency plan: Use *hydrocortisone 0.1 % cream* for mild eczema but layer with an emollient to reduce the risk of systemic absorption.
• Tapering schedule: 1 mg/kg/sq/day for the first week, then reduce 20 % each following week; use patient‑specific clinical judgment.
• Drug interactions: Concomitant ketoconazole or cimetidine can raise hydrocortisone levels; adjust dose accordingly.
• Precision dosing for pediatrics: Use mg/kg formula; avoid > 2 mg/kg/day orally.

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• *Hydrocortisone* remains the cornerstone glucocorticoid for a wide spectrum of inflammatory, immunologic, and endocrine conditions. Proper regimen design, vigilant monitoring, and understanding of its pharmacokinetic profile ensure maximal therapeutic benefit with minimal adverse impact.