Prednisone
Prednisone
Generic Name
Prednisone
Mechanism
Prednisone is a synthetic glucocorticoid.
• Genomic (classical) pathway:
• It crosses cell membranes → binds cytoplasmic glucocorticoid receptors → translocates to the nucleus → alters transcription of anti‑inflammatory and immunosuppressive genes (e.g., ↑IL‑10, ↓TNF‑α, ↓IL‑1β).
• Non‑genomic pathway:
• Rapid modulation of membrane‑bound receptors and second‑messenger systems (Ca²⁺, MAPK) → quick suppression of edema, vasodilation, and leukocyte infiltration.
• Net effect: potent inhibition of prostaglandin, leukotriene, and cytokine synthesis, decreased mast‑cell degranulation, and reduced leukocyte recruitment.
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Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral bioavailability >99 %; peak plasma 1–2 hrs (after 1 – 2 hrs). |
| Distribution | Highly protein‑bound (~90 % albumin); penetrates CNS, placenta, and most tissues. |
| Metabolism | Hepatic conversion (CYP3A4) to active prednisolone (≈ 15 % of dose). First‑pass effect minimal. |
| Elimination | Renal excretion of metabolites; half‑life ~3 – 4 hrs (systemic glucocorticoid action ~12 hrs). |
| Drug interactions | CYP3A4 inducers ↑ elimination → ↓ efficacy; inhibitors ↑ exposure → ↑ adverse events. |
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Indications
- Autoimmune & inflammatory disorders
- Rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease.
- Asthma & allergic reactions
- Severe asthma exacerbations, anaphylaxis, urticaria.
- Adrenal insufficiency prophylaxis
- Surgery, high‑dose radiation therapy.
- Organ transplantation
- Acute rejection prophylaxis/intensification.
- Dermatologic conditions
- Severe eczema, psoriasis flares.
- Neurologic & ophthalmic
- Optic neuritis, stroke‑related cerebral edema, uveitis.
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Contraindications
| Category | Notes |
| Absolute Contraindications |
* Live or uncontrolled fungal infections (e.g., candidiasis, cryptococcosis). |
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* Untreated systemic bacterial or viral infection. |
| Relative Contraindications |
* Active peptic ulcer disease. |
* Severe hypertension or cardiac failure. |
| Warnings |
* Immunosuppression → ↑ risk of opportunistic infections. |
* Hyperglycemia and new-onset diabetes. |
* Osteoporosis and avascular necrosis. |
* Adrenal suppression → risk of adrenal crisis during stress. |
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Dosing
| Condition | Typical Regimen |
| Adult systemic therapy | 5–60 mg PO daily for 3–7 days; taper by 10–20 % per week based on response. |
| Severe asthma exacerbation | 40–60 mg IV/IV + oral taper over 1–2 weeks. |
| Dermatologic flare | 0.5–2 mg/kg PO/IV; taper based on skin response. |
| Pediatric | 0.5–2 mg/kg / day (max 80 mg) → taper. |
Tips
• Transition to oral: Prefer the oral regimen once the patient tolerates PO.
• Taper: Reduce dose by 10–25 % every 1–2 weeks; longer taper for prolonged use.
• Adjust for comorbidities: Lower dose for diabetics, frail elderly, or those on nephrotoxic drugs.
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Adverse Effects
| Category | Examples |
| Common | Nausea, insomnia, mood swings, increased appetite, weight gain, central obesity, cushingoid facies, hypertension, hyperglycemia. |
| Serious | Adrenal insufficiency, opportunistic infections (e.g., Pneumocystis jirovecii), peptic ulcer perforation, psychosis, osteonecrosis, cataracts, myopathy. |
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Monitoring
- Baseline: CBC, CMP (glucose, electrolytes), fasting lipid panel, BP, weight.
- During therapy:
- Glucose: Every 4–6 hr in high‑dose or diabetics.
- Blood pressure: Weekly for 8–12 weeks; more often if unstable.
- Bone density: DEXA at 6–12 mo if ≥6 mo therapy.
- Follow‑up:
- Assess adrenal reserve via cosyntropin test if ≥3 weeks of high‑dose or taper completion.
- Periodic ophthalmologic exam for long‑term use.
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Clinical Pearls
- “Rule of 3” for adrenal crisis:
*If a patient on prednisone >7 days is hospitalized for a non‑steroid illness, give 100 mg IV methylprednisolone as a bridge.*
• Vaccination strategy:
*Administer live‑attenuated vaccines at least 4 weeks before initiating prednisone; defer if dose >20 mg/day.*
• Use of PPIs:
*Co‑prescribe a proton‑pump inhibitor for patients on >20 mg/day to reduce gastric ulcer risk.*
• Glucocorticoid‑induced mood changes:
*Monitor psychiatric symptoms; consider lower maintenance dose or add anxiolytics if anxiety/panic develops.*
• Taper schedule significance:
*Skipping a taper step (>20 % reduction) can precipitate adrenal insufficiency; always follow a gradual taper.*
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• Key Takeaway:
Prednisone is a versatile, potent systemic glucocorticoid with a rapid onset of action and broad therapeutic applications. Mastery of its dosing, tapering, and side‑effect management is essential for safe practice.