Hydrocortisone
1. Drug Name
Generic Name: Hydrocortisone
Brand Names: Cortef, Solu-Cortef, Hydrocortone, A-Hydrocortisone, and others.
2. Drug Classification
Class: Corticosteroid
Subclass: Glucocorticoid
Other Classifications: Anti-inflammatory, Immunosuppressant
3. Mechanism of Action
Glucocorticoid Receptor Binding: Hydrocortisone acts by binding to glucocorticoid receptors in the cytoplasm, forming a glucocorticoid-receptor complex. This complex translocates to the nucleus, where it influences gene transcription, modulating the expression of anti-inflammatory genes and suppressing pro-inflammatory cytokines.
Anti-inflammatory Effects: Hydrocortisone inhibits the production of key inflammatory mediators, such as prostaglandins, leukotrienes, and cytokines, thereby reducing inflammation. It also decreases the recruitment and activation of inflammatory cells (e.g., neutrophils, macrophages).
Immunosuppressive Effects: By suppressing the immune system, hydrocortisone helps reduce tissue damage caused by overactive immune responses. It also inhibits the formation of antibodies and reduces the synthesis of histamine and other pro-inflammatory mediators.
Metabolic Effects: Hydrocortisone increases gluconeogenesis (formation of glucose from non-carbohydrate sources) and promotes protein catabolism. It also enhances the breakdown of fats, increasing fatty acids in the bloodstream.
4. Pharmacokinetics
Absorption:
Hydrocortisone is well absorbed when administered orally or parenterally (intravenous or intramuscular routes).
When taken orally, the bioavailability is around 70-90%. For intravenous or intramuscular administration, it is 100% bioavailable.
Distribution:
Volume of Distribution (Vd): Hydrocortisone is widely distributed throughout the body, including the brain, liver, and kidneys. It is 90–95% bound to plasma proteins, primarily corticosteroid-binding globulin (CBG) and albumin.
It crosses the placenta and is excreted in breast milk.
Metabolism:
Hydrocortisone is primarily metabolized in the liver by enzymes such as CYP3A4, producing inactive metabolites (mainly tetrahydrocortisone and 11β-hydroxyhydrocortisone) that are later excreted in the urine.
Excretion:
Half-life (t½): The terminal half-life of hydrocortisone varies depending on the route of administration and individual patient factors but typically ranges from 8 to 12 hours after oral administration.
Hydrocortisone is mainly excreted by the kidneys in the form of metabolites.
5. Indications
Primary Indications:
Adrenal Insufficiency: Hydrocortisone is used to treat primary or secondary adrenal insufficiency (Addison’s disease), where the adrenal glands fail to produce adequate cortisol.
Acute and Chronic Inflammatory Conditions: It is used to manage inflammatory conditions like rheumatoid arthritis, ulcerative colitis, and Crohn's disease.
Allergic Reactions: Hydrocortisone is used in the treatment of severe allergic reactions, including anaphylaxis, in combination with other agents like epinephrine.
Acute Asthma Exacerbations: It is used in the treatment of severe asthma exacerbations, often as part of emergency therapy.
Dermatologic Conditions: Topical hydrocortisone is used for inflammatory skin conditions such as eczema, psoriasis, and dermatitis.
Off-label Uses:
Shock: In cases of septic shock or anaphylactic shock, hydrocortisone may be administered to reduce systemic inflammation and support cardiovascular stability.
Cerebral Edema: It is used in cases of cerebral edema (swelling of the brain) due to various causes, including brain tumors or traumatic brain injury.
Acute Spinal Cord Injury: Hydrocortisone has been explored in acute spinal cord injury to reduce inflammation and minimize damage.
6. Dosage and Administration
Adult Dosing:
Adrenal Insufficiency: The typical oral dose is 20–30 mg daily, divided into 2-3 doses. In times of stress or illness, the dose may need to be increased.
Rheumatoid Arthritis: 20–40 mg daily, adjusted based on response.
Acute Asthma Exacerbation: Intravenous hydrocortisone is typically administered as 100–200 mg every 4-6 hours, with tapering as improvement is seen.
Topical Use (Dermatologic Conditions): Apply a thin film of 0.5%–2.5% cream or ointment to the affected area 1–3 times daily.
Pediatric Dosing:
Adrenal Insufficiency: 5–10 mg/m² daily, given in 2–3 divided doses.
Allergic Conditions: 0.5–2 mg/kg/day depending on severity.
Renal and Hepatic Adjustments:
Dose adjustments are not typically required in renal impairment for standard doses.
Hepatic impairment may require reduced dosing due to decreased metabolism of hydrocortisone, especially in severe liver disease.
7. Contraindications
Absolute Contraindications:
Hypersensitivity: Known hypersensitivity to hydrocortisone or any of its excipients.
Systemic Fungal Infections: Hydrocortisone may exacerbate systemic fungal infections.
Relative Contraindications:
Active Infections: Active tuberculosis, herpes simplex, and varicella infections may worsen under corticosteroid treatment.
Peptic Ulcer Disease: Use cautiously as corticosteroids can exacerbate ulcers or cause gastrointestinal bleeding.
8. Warnings and Precautions
Infection Risk: Hydrocortisone can suppress the immune response, increasing susceptibility to infections. Prophylactic antimicrobial treatment may be needed in certain high-risk patients.
Endocrine Effects: Chronic use may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis, adrenal suppression, and secondary adrenal insufficiency. Patients should be tapered off corticosteroids gradually to allow adrenal recovery.
Cardiovascular Effects: Long-term use may lead to hypertension, fluid retention, and electrolyte imbalances (e.g., hypokalemia).
Psychiatric Effects: Some patients may experience mood changes, euphoria, insomnia, or depression, particularly with long-term use.
Osteoporosis: Long-term corticosteroid therapy can lead to bone loss and an increased risk of fractures.
9. Adverse Effects
Common Adverse Effects:
Weight Gain: Often due to fluid retention and increased appetite.
Increased Blood Pressure: Corticosteroids can lead to hypertension.
Hyperglycemia: May exacerbate existing diabetes or cause new-onset diabetes.
Less Common but Clinically Significant:
Osteoporosis: Chronic use leads to bone thinning and an increased risk of fractures.
Cataracts and Glaucoma: Long-term use increases the risk of developing cataracts or elevated intraocular pressure.
Gastrointestinal Bleeding: Especially in patients with a history of peptic ulcers.
Rare/Serious Adverse Reactions:
Adrenal Crisis: Abrupt discontinuation or excessive dosing can lead to adrenal insufficiency.
Cushing's Syndrome: Chronic use may lead to features of Cushing's syndrome, such as moon face, buffalo hump, and thinning skin.
10. Drug Interactions
Cytochrome P450 Enzyme Interactions: Hydrocortisone is metabolized by CYP3A4, and drugs that inhibit this enzyme (e.g., ketoconazole, ritonavir) may increase its plasma concentrations.
Diuretics: Diuretics can increase the risk of hypokalemia when used in conjunction with hydrocortisone, as corticosteroids can promote potassium loss.
NSAIDs: Concurrent use of hydrocortisone with NSAIDs may increase the risk of gastrointestinal ulcers and bleeding.
11. Clinical Pharmacology
Pharmacodynamics: Hydrocortisone exerts potent anti-inflammatory and immunosuppressive effects, making it effective in managing conditions like arthritis, allergies, and asthma. It works by inhibiting the inflammatory cascade and modulating immune responses.
Corticosteroid Effects: Apart from inflammation, hydrocortisone impacts the metabolism of carbohydrates, proteins, and fats, leading to its catabolic and hyperglycemic effects.
12. Special Populations
Pregnancy: Category C. Hydrocortisone should be used during pregnancy only if the benefits outweigh the risks. It may cause fetal harm in high doses.
Lactation: Hydrocortisone is excreted in breast milk, but its use is generally considered safe for short-term treatment in lactating women.
Pediatrics: Growth should be monitored in children receiving long-term corticosteroid therapy. Dose reduction and careful monitoring are advised.
Geriatrics: Older adults may be more sensitive to the side effects, such as osteoporosis, cataracts, and cardiovascular effects.
13. Therapeutic Uses
Primary: Hydrocortisone is used for the treatment of adrenal insufficiency, allergic conditions, rheumatoid arthritis, and certain dermatologic disorders.
Secondary: It can be used for acute exacerbations of asthma and COPD as well as in shock management.
Off-label: Also used in treating cerebral edema, septic shock, and acute spinal cord injuries.
14. Monitoring and Follow-Up
Blood Pressure and Electrolytes: Regular monitoring of blood pressure and serum electrolytes (especially potassium and sodium) is recommended.
Blood Glucose: Monitor blood glucose levels in diabetic or pre-diabetic patients.
Bone Density: For long-term use, assess bone mineral density and consider calcium and vitamin D supplementation.
15. Overdose Management
Symptoms of Overdose: Chronic overdose may lead to Cushing’s syndrome, hyperglycemia, and fluid retention.
Management: Overdose treatment involves supportive care, with possible dose reduction and symptom management.
16. Patient Counseling Information
Administration: Take oral hydrocortisone with food to reduce gastrointestinal irritation. For injectable forms, administration should only be done by healthcare professionals.
Potential Side Effects: Advise patients to report signs of infection, mood changes, weight gain, or changes in blood sugar levels.
Tapering: Do not abruptly discontinue hydrocortisone after prolonged use; it should be tapered gradually under a doctor’s guidance.