Hydrocortisone

Uses

Hydrocortisone, a synthetic corticosteroid, is widely utilized due to its potent anti-inflammatory and glucocorticoid properties. Key indications include:

1. Adrenal Insufficiency:

   • Replacement therapy in primary and secondary adrenal insufficiency (e.g., Addison’s disease, pituitary disorders).
   • Management of adrenal crisis in acute settings.

2. Inflammatory and Allergic Conditions:

   • Treatment of severe allergic reactions, drug hypersensitivity, urticaria, and angioedema.

3. Septic Shock:

   • Adjunctive therapy for hemodynamic stabilization in refractory septic shock.

4. Cerebral Edema:

   • Reduces brain swelling associated with tumors, trauma, or meningitis.

5. Acute Asthma and COPD Exacerbations:

   • Reduces airway inflammation in severe cases.

6. Rheumatologic and Autoimmune Disorders:

   • Management of systemic lupus erythematosus, rheumatoid arthritis, and polymyalgia rheumatica during acute flares.

7. Dermatologic Disorders:

   • Treatment of severe inflammatory skin conditions, including eczema and psoriasis.

Dosage and Administration

Acute Management

• Initial Dose:
  • 1–2 mg/kg/dose IV every 6 hours.
• Maintenance Dose:
  • 0.5–1 mg/kg IV or PO every 6 hours, depending on severity and response.

Adrenal Crisis

• Adults:
  • 100 mg IV bolus, followed by 50 mg IV every 6–8 hours for 24–48 hours.
• Children:
  • 2–4 mg/kg IV bolus, then 1 mg/kg every 6 hours, followed by tapering based on clinical need.

Septic Shock

• Hydrocortisone Infusion:
  • 200 mg/day as a continuous infusion or divided into 50 mg IV every 6 hours.

Chronic Replacement Therapy

• Adults:
  • 15–25 mg/day orally in divided doses (10 mg in the morning, 5 mg in the afternoon).
• Children:
  • 8–10 mg/m²/day orally in two divided doses.

Presentation

1. Oral Tablets: 5 mg, 10 mg, 20 mg.
2. Injectable Solution: 100 mg, 250 mg, 500 mg, and 1 g vials.
3. Topical Formulations: Available for dermatological use in various strengths.

Pharmacokinetics

1. Absorption:

   • Rapidly absorbed after oral administration with a bioavailability of approximately 96%.

2. Distribution:

   • Binds extensively to plasma proteins (corticosteroid-binding globulin and albumin).
   • Volume of distribution: 0.4–0.6 L/kg.

3. Metabolism:

   • Primarily metabolized in the liver to inactive metabolites (e.g., tetrahydrocortisol and tetrahydrocortisone).

4. Excretion:

   • Eliminated via the kidneys, with 70–80% excreted as metabolites.

5. Plasma Half-Life:

   • Biological half-life: 8–12 hours.
   • Plasma half-life: 1.5–2 hours.

Pharmacodynamics

Hydrocortisone mimics the endogenous hormone cortisol and exhibits its effects by binding to glucocorticoid receptors. This interaction:

1. Reduces Inflammation:

   • Inhibits prostaglandin and leukotriene synthesis by blocking arachidonic acid release.

2. Suppresses Immune Response:

   • Decreases cytokine production and immune cell activation.

3. Stabilizes Cell Membranes:

   • Prevents capillary leakage and reduces edema.

4. Regulates Metabolism:

   • Promotes gluconeogenesis, protein catabolism, and lipolysis, contributing to hyperglycemia.

Precautions and Monitoring

1. Tapering:

   • Gradual reduction is necessary after prolonged therapy to avoid adrenal insufficiency.

2. Diabetes and Hypertension:

   • Can exacerbate hyperglycemia and elevate blood pressure; regular monitoring is essential.

3. Infection Risk:

   • Immunosuppressive effects increase susceptibility to infections.

4. Peptic Ulcer Disease:

   • Use cautiously in patients with a history of ulcers.

5. Psychiatric Effects:

   • High doses may cause mood changes, insomnia, or steroid-induced psychosis.

Side Effects

Common:

• Weight gain, increased appetite.
• Insomnia, restlessness.
• Hypertension, hyperglycemia.

Serious:

• Adrenal suppression.
• Osteoporosis with prolonged use.
• Peptic ulcers and gastrointestinal bleeding.
• Secondary infections due to immunosuppression.

Recent Updates and Guidelines

1. Surviving Sepsis Campaign Guidelines (2023):

   • Recommends hydrocortisone for refractory septic shock unresponsive to fluids and vasopressors.

2. Endocrine Society Clinical Practice Guideline (2022):

   • Highlights stress dosing during acute illness or surgery in patients with adrenal insufficiency.

3. Global Initiative for Asthma (GINA 2023):

   • Endorses systemic corticosteroids, including hydrocortisone, for severe asthma exacerbations.

4. FDA Communication (2020):

   • Reinforces the need for monitoring secondary infections during corticosteroid therapy.

References

1. Surviving Sepsis Campaign Guidelines (2023).
2. Endocrine Society Clinical Practice Guideline: Adrenal Insufficiency (2022).
3. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics (13th Edition).
4. Global Initiative for Asthma (GINA) Report (2023).
5. FDA Drug Safety Communication: Risks Associated with Corticosteroids (2020).

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