Prednisone
1. Drug Name
Generic Name: Prednisone
Brand Names: Deltasone, Rayos, Prednicot, Sterapred, and others
2. Drug Classification
Class: Corticosteroid (Glucocorticoid)
Subclass: Synthetic Glucocorticoid
Other Classifications: Anti-inflammatory, Immunosuppressant
3. Mechanism of Action
Glucocorticoid Receptor Activation: Prednisone exerts its effects through binding to glucocorticoid receptors located in various tissues, including the liver, muscle, and immune cells. This interaction results in gene transcription changes that modulate a variety of physiological processes.
Anti-inflammatory Effects: Prednisone inhibits the expression of pro-inflammatory cytokines (e.g., interleukins, tumor necrosis factor) by suppressing the transcription of genes encoding these molecules. It also inhibits phospholipase A2, thereby reducing the production of arachidonic acid and the subsequent synthesis of inflammatory mediators like prostaglandins and leukotrienes.
Immunosuppressive Effects: It suppresses immune system activity by inhibiting the migration of leukocytes to sites of inflammation and suppressing the production of antibodies, T lymphocyte activation, and cytokine release.
Metabolic Effects: Prednisone affects carbohydrate, fat, and protein metabolism. It can increase glucose production by the liver (gluconeogenesis), decrease glucose uptake by cells, and promote protein breakdown, leading to muscle wasting and fat redistribution.
4. Pharmacokinetics
Absorption:
Bioavailability: Prednisone is well absorbed after oral administration, with a bioavailability of approximately 70-90%.
Onset of Action: Oral prednisone typically takes 1 to 2 hours to begin working, with peak effects seen within 6-12 hours, depending on the dose and condition being treated.
Distribution:
Volume of Distribution (Vd): The volume of distribution is variable, ranging from 0.3 to 1.2 L/kg, depending on the body mass and clinical condition.
Protein Binding: Prednisone is 60-90% bound to plasma proteins, primarily corticosteroid-binding globulin and albumin.
Metabolism:
Liver Metabolism: Prednisone is a prodrug and is metabolized in the liver to its active form, prednisolone, by 11β-hydroxysteroid dehydrogenase. This conversion is crucial for its therapeutic effect.
Enzymes Involved: Prednisone is metabolized by cytochrome P450 enzymes, particularly CYP3A4.
Excretion:
Half-life (t½): The elimination half-life of prednisone is approximately 3-4 hours, but this can be longer in patients with liver impairment.
Excretion: Prednisone and its metabolites are excreted in the urine. Only a small fraction of the drug is excreted unchanged.
Special Considerations:
Hepatic Impairment: In patients with hepatic dysfunction, the conversion of prednisone to prednisolone may be impaired, potentially reducing its efficacy.
Renal Impairment: Renal failure does not significantly affect prednisone metabolism, but care should be taken when adjusting doses in patients with renal disease due to the risk of electrolyte imbalances.
5. Indications
Primary Indications:
Inflammatory Conditions: Used for a wide range of inflammatory conditions, such as rheumatoid arthritis, lupus, and inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease).
Allergic Reactions: Effective for severe allergic reactions, including asthma exacerbations, drug allergies, and skin conditions like dermatitis.
Autoimmune Diseases: Used for treating autoimmune diseases such as multiple sclerosis, vasculitis, and autoimmune hemolytic anemia.
Adrenal Insufficiency: Used to replace endogenous corticosteroid production in conditions like Addison’s disease.
Neoplastic Conditions: Used as part of combination therapy in certain cancers (e.g., leukemia, lymphoma) to reduce inflammation and as part of chemotherapy regimens.
Off-label Uses:
Acute Respiratory Distress Syndrome (ARDS): Inflammation in the lungs in ARDS can be treated with corticosteroids, though the evidence for its efficacy in ARDS is mixed.
Severe Acute Allergic Reactions: Such as anaphylaxis after the initial epinephrine administration.
Cerebral Edema: For patients with brain tumors or brain injury to reduce swelling and pressure.
6. Dosage and Administration
Adult Dosing:
Inflammatory Conditions: The typical initial dose ranges from 5 to 60 mg daily, depending on the severity of the condition. The dose is often tapered after a few days to minimize side effects.
Adrenal Insufficiency: 20-30 mg per day, taken in the morning, as part of replacement therapy.
Acute Allergic Reactions: 20-40 mg daily for a few days, tapered based on clinical response.
Pediatric Dosing:
Asthma or Allergic Conditions: 0.5-2 mg/kg/day, divided into 1-2 doses.
Acute Inflammatory Conditions: Dose varies by condition and severity, typically ranging from 1-2 mg/kg/day.
Special Dosing Considerations:
Renal or Hepatic Impairment: Dosing may need adjustment, particularly in hepatic dysfunction due to reduced metabolism of prednisone to prednisolone.
7. Contraindications
Absolute Contraindications:
Systemic Fungal Infections: Prednisone is contraindicated in patients with systemic fungal infections as it may suppress the immune system and worsen the condition.
Hypersensitivity: Known hypersensitivity to prednisone or any of its components.
Relative Contraindications:
Active Tuberculosis: Caution is advised, as prednisone can increase the risk of active tuberculosis.
Peptic Ulcer Disease: Prednisone may exacerbate gastric ulcers and should be used with caution in individuals with a history of peptic ulcers.
Psychiatric Disorders: Long-term use of corticosteroids may exacerbate psychiatric conditions such as depression or psychosis.
8. Warnings and Precautions
Infection Risk: Prolonged use of corticosteroids like prednisone can suppress the immune system, increasing susceptibility to infections, including opportunistic infections like tuberculosis.
Gastrointestinal Bleeding: Steroid use can lead to gastric ulcers, gastrointestinal bleeding, and perforation, especially in elderly patients and those taking NSAIDs concurrently.
Osteoporosis: Long-term prednisone use can lead to osteoporosis and fractures due to its effect on calcium metabolism and bone resorption.
Endocrine Effects: Chronic use of prednisone can lead to adrenal suppression, requiring careful tapering when discontinuing the drug to avoid adrenal crisis.
Cushing's Syndrome: Prolonged therapy may cause Cushing's syndrome, which includes features like weight gain, moon face, and central obesity.
Psychiatric Effects: It can cause mood swings, anxiety, and even psychosis or depression, especially with long-term use.
9. Adverse Effects
Common Adverse Effects:
Weight Gain: Often seen due to fluid retention and increased appetite.
Fluid Retention: Prednisone may cause peripheral edema, which is especially noticeable in the lower limbs.
Increased Blood Sugar: May lead to hyperglycemia, particularly in diabetic patients.
Less Common but Clinically Significant:
Hypertension: Steroids like prednisone can increase blood pressure.
Gastrointestinal Symptoms: Including dyspepsia, gastric ulcers, and risk of gastrointestinal bleeding.
Rare/Serious Adverse Reactions:
Osteoporosis: Long-term use can lead to brittle bones and increased risk of fractures.
Psychiatric Disturbances: Severe mood swings, depression, psychosis, or cognitive impairment.
Adrenal Insufficiency: Abrupt discontinuation of prednisone after long-term use can lead to adrenal crisis, characterized by hypotension, hypoglycemia, and fatigue.
10. Drug Interactions
Cytochrome P450 Inhibitors/Inducers: Drugs such as ketoconazole (CYP3A4 inhibitor) can increase prednisone levels, while rifampin (CYP3A4 inducer) can decrease its levels.
NSAIDs: Concomitant use with NSAIDs increases the risk of gastrointestinal bleeding and ulcers.
Diuretics: Prednisone may enhance the hypokalemic effect of diuretics, leading to low potassium levels.
Vaccines: Live vaccines (e.g., measles, mumps, rubella) should be avoided during long-term corticosteroid therapy due to the increased risk of infection.
11. Clinical Pharmacology
Pharmacodynamics: Prednisone’s anti-inflammatory and immunosuppressive actions are mediated through glucocorticoid receptor binding and gene expression modulation, leading to reduced production of inflammatory mediators and suppression of immune responses.
Additional Effects: Aside from its primary use in inflammatory and autoimmune conditions, prednisone also affects electrolyte balance and glucose metabolism, leading to complications like hyperglycemia, sodium retention, and potassium loss.
12. Special Populations
Pregnancy: Category C. Use during pregnancy should be avoided unless the benefits outweigh the risks, particularly in the first trimester.
Lactation: Prednisone is excreted into breast milk in low concentrations. Short-term use is considered acceptable, but prolonged use should be avoided during breastfeeding.
Pediatrics: Prednisone is used in children for various conditions like asthma, autoimmune diseases, and certain allergic conditions, though caution is needed due to its potential effects on growth and development.
Geriatrics: Elderly patients are at higher risk for side effects such as osteoporosis, hypertension, and gastrointestinal bleeding. Lower doses are often used in elderly patients.
13. Therapeutic Uses
Primary: Used in treating inflammatory diseases (e.g., rheumatoid arthritis), autoimmune disorders (e.g., lupus), and conditions like asthma and allergic reactions.
Combinational Therapy: Often used in combination with other immunosuppressive agents in the treatment of cancers, such as lymphomas and leukemia.
14. Monitoring and Follow-Up
Blood Pressure Monitoring: Monitor for hypertension, especially in patients on long-term therapy.
Blood Glucose: Regular monitoring for hyperglycemia is essential, especially in diabetic patients.
Bone Density: Long-term use requires monitoring for osteoporosis and fractures.
Electrolytes: Potassium levels should be monitored due to the risk of hypokalemia.
15. Overdose Management
Symptoms of Overdose: Symptoms include hyperglycemia, fluid retention, high blood pressure, and gastrointestinal bleeding.
Management: There is no specific antidote for prednisone overdose. Treatment focuses on managing symptoms, including monitoring electrolytes, glucose levels, and vital signs.
16. Patient Counseling Information
Administration: Take prednisone with food or milk to reduce gastrointestinal irritation. Follow the prescribed dosing schedule and taper off slowly to avoid withdrawal symptoms.
Avoid Alcohol: Alcohol should be avoided to minimize the risk of gastrointestinal side effects and peptic ulceration.
Monitoring for Side Effects: Patients should be informed of potential side effects, including weight gain, swelling, and increased blood sugar, and advised to seek medical attention if these occur.