Hydrocortisone

Usage

Hydrocortisone is a glucocorticoid, a class of corticosteroids, prescribed for a wide range of medical conditions. It is used to treat adrenocortical insufficiency, inflammatory and rheumatic disorders, allergic conditions, certain skin diseases, respiratory problems like asthma and COPD, certain cancers, and other conditions where its anti-inflammatory and immunosuppressive actions are beneficial. Its pharmacological classifications include corticosteroid, anti-inflammatory, antipruritic, and antiallergic.

Hydrocortisone mimics the action of cortisol, a hormone naturally produced by the adrenal glands. It exerts its effects by binding to glucocorticoid receptors in the cytoplasm of target cells. This complex then translocates to the nucleus, where it modulates the transcription of various genes involved in inflammation, immune response, and metabolism.

Alternate Names

Hydrocortisone is also known as cortisol. Brand names for hydrocortisone include Cortef, Solu-Cortef, Hydrocortisone–AFT, and others depending on the formulation and region. Plenadren is a brand name for modified-release hydrocortisone.

How It Works

Pharmacodynamics: Hydrocortisone binds to glucocorticoid receptors, leading to decreased inflammation, immunosuppression, and changes in metabolism. It inhibits inflammatory mediators like prostaglandins and leukotrienes, reduces capillary permeability, and suppresses leukocyte migration.

Pharmacokinetics: Hydrocortisone can be administered orally, intravenously, intramuscularly, topically, or rectally. Absorption varies depending on the route of administration. It is metabolized primarily in the liver by CYP3A4 enzymes and excreted by the kidneys.

Mode of Action: The hydrocortisone-receptor complex binds to specific DNA sequences called glucocorticoid response elements, affecting gene expression. It can also interact with other transcription factors, modulating their activity.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Hydrocortisone primarily binds to glucocorticoid receptors. It inhibits phospholipase A2, reducing the production of arachidonic acid and downstream inflammatory mediators.

Elimination Pathways: Hydrocortisone is metabolized in the liver, primarily by CYP3A4, and excreted in the urine.

Dosage

Dosages vary significantly based on the condition being treated, route of administration, and patient-specific factors.

Standard Dosage

Adults:

Oral: 10-320 mg/day, divided into several doses. Intravenous/Intramuscular: 100-500 mg initially, repeated as needed every 2, 4, or 6 hours.

Children:

Dosing is typically based on body weight or body surface area (BSA) and varies widely depending on the indication. For example, in adrenocortical insufficiency, children might receive 1-2 mg/kg IV every 6 hours initially, with a maximum dose of 250 mg. Pediatric dosing requires careful consideration of growth and development, as well as potential long-term effects on bone health and growth suppression with prolonged use.

Special Cases:

• Elderly Patients: Start with lower doses and monitor closely for side effects. Dose adjustments may be necessary due to age-related decline in organ function.
• Patients with Renal Impairment: Dose adjustments may be required in severe renal impairment. Monitor renal function and adjust accordingly.
• Patients with Hepatic Dysfunction: No dose adjustment is recommended for mild to moderate hepatic impairment. In severe hepatic impairment, monitor closely and consider dose adjustments.
• Patients with Comorbid Conditions: Dosage adjustments may be required in patients with diabetes, cardiovascular disease, or other comorbid conditions. Monitor closely for adverse effects and disease-specific complications.

Clinical Use Cases:

• Intubation: In patients with known or suspected adrenal insufficiency, a hydrocortisone bolus (e.g., 100 mg IV) may be given prior to intubation.
• Surgical Procedures: Patients on chronic glucocorticoid therapy often require stress-dose hydrocortisone before, during, and after surgery to prevent adrenal crisis. Doses and regimens vary depending on the magnitude of the surgery. For major surgery, 100mg IV at induction followed by 100mg every 6 hours or 200mg continuous IV infusion over 24 hours.
• Mechanical Ventilation: In patients with sepsis and septic shock requiring vasopressor support, hydrocortisone 200mg/day is often administered.
• Intensive Care Unit (ICU) Use: Hydrocortisone is often used for the management of critical illness-related corticosteroid insufficiency (CIRCI) and septic shock.
• Emergency Situations: In adrenal crisis, 100 mg hydrocortisone IV bolus is given, followed by continuous infusion or divided doses. For status epilepticus, higher doses (e.g., 18 mg/kg, max 1800 mg) of IV hydrocortisone may be used.

Dosage Adjustments:

Dose modifications are based on patient response, disease severity, and the presence of renal or hepatic dysfunction. Therapeutic drug monitoring and close clinical observation are crucial for optimizing therapy and minimizing adverse events.

Side Effects

Common Side Effects:

Fluid retention, weight gain, increased appetite, mood changes, insomnia, hyperglycemia, increased susceptibility to infections.

Rare but Serious Side Effects:

Peptic ulcers, osteoporosis, avascular necrosis, adrenal suppression, Cushing’s syndrome, psychosis, allergic reactions.

Long-Term Effects:

Growth retardation in children, osteoporosis, cataracts, glaucoma, diabetes, hypertension, increased risk of infections.

Adverse Drug Reactions (ADR):

Severe allergic reactions (anaphylaxis), adrenal crisis (upon abrupt discontinuation), hypertensive crisis, hyperglycemia, severe infections.

Contraindications

Hypersensitivity to hydrocortisone, systemic fungal infections, serious infections (unless specific anti-infective therapy is employed concurrently), vaccination with live virus vaccines (in patients receiving immunosuppressive doses).

Drug Interactions

Hydrocortisone interacts with numerous medications, including:

• CYP3A4 Inducers/Inhibitors: These alter hydrocortisone metabolism.
• Anticholinesterases: May exacerbate weakness in myasthenia gravis.
• Anticoagulants: Effects may be enhanced or reduced.
• Antidiabetics: Hydrocortisone can increase blood glucose, counteracting antidiabetic effects.
• NSAIDs: Increased risk of gastrointestinal bleeding.
• Potassium-depleting diuretics: Increased risk of hypokalemia.

Interactions with OTC drugs, supplements, alcohol, and grapefruit juice are also possible.

Pregnancy and Breastfeeding

Hydrocortisone is generally considered safe during pregnancy but should be used only when clearly needed. It is excreted in breast milk, but the effects on nursing infants are not fully known.

Drug Profile Summary

• Mechanism of Action: Binds to glucocorticoid receptors, modulating gene expression and affecting inflammation, immune response, and metabolism.
• Side Effects: Fluid retention, weight gain, hyperglycemia, increased risk of infections, osteoporosis (long-term use).
• Contraindications: Systemic fungal infections, serious infections, hypersensitivity.
• Drug Interactions: CYP3A4 inducers/inhibitors, anticoagulants, antidiabetics, NSAIDs.
• Pregnancy & Breastfeeding: Generally safe during pregnancy when needed; excreted in breast milk.
• Dosage: Highly variable depending on indication and patient factors.
• Monitoring Parameters: Blood glucose, electrolytes, blood pressure, signs of infection, growth in children (with long-term use).

Popular Combinations

Hydrocortisone is often combined with mineralocorticoids (like fludrocortisone) in adrenal insufficiency. It may also be used with other medications for specific conditions (e.g., bronchodilators in asthma).

Precautions

General precautions include screening for infections, diabetes, hypertension, osteoporosis, and other conditions that might be exacerbated by hydrocortisone. Specific precautions apply to pregnant/breastfeeding women, children, elderly individuals, and patients with hepatic or renal dysfunction. Lifestyle considerations include limiting alcohol and sodium intake, and avoiding exposure to infections.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Hydrocortisone?

A: Hydrocortisone dosing is highly individualized and dependent on the specific indication. Dosages can range from 10-320 mg/day orally or 100-500 mg IV/IM initially, with adjustments made based on the patient’s condition and response to therapy. Pediatric dosing is based on weight or BSA.

Q2: What are the common side effects of Hydrocortisone?

A: Common side effects include fluid retention, weight gain, increased appetite, mood changes, difficulty sleeping, and elevated blood sugar.

Q3: What are the serious side effects of Hydrocortisone?

A: Serious side effects include peptic ulcers, osteoporosis, avascular necrosis, adrenal suppression, Cushing’s syndrome, psychosis, and severe allergic reactions.

Q4: How should Hydrocortisone be administered?

A: Hydrocortisone can be administered orally, intravenously, intramuscularly, topically, or rectally, depending on the condition being treated and the required speed of onset.

Q5: What are the contraindications for using Hydrocortisone?

A: Contraindications include hypersensitivity to hydrocortisone, systemic fungal infections, serious infections (unless covered by specific anti-infective therapy), and live virus vaccination in immunosuppressed patients.

Q6: How should Hydrocortisone be dosed in patients with renal impairment?

A: Dose adjustments may be necessary in patients with severe renal impairment. Close monitoring of renal function is required.

Q7: Does Hydrocortisone interact with other medications?

A: Yes, hydrocortisone interacts with a wide range of medications, including CYP3A4 inducers/inhibitors, anticoagulants, antidiabetics, NSAIDs, and potassium-depleting diuretics. A thorough medication review is essential before initiating hydrocortisone therapy.

Q8: Can Hydrocortisone be used during pregnancy?

A: Hydrocortisone is generally considered safe during pregnancy but should only be used when clearly needed and under close medical supervision.

Q9: What monitoring parameters are important when a patient is on Hydrocortisone?

A: Monitoring should include blood glucose, electrolytes, blood pressure, signs and symptoms of infection, and assessment of growth in children receiving long-term therapy.

Q10: What precautions should be taken when prescribing Hydrocortisone to elderly patients?

A: Start with lower doses and monitor carefully for side effects due to age-related changes in physiology and organ function.