Methylprednisolone
Methylprednisolone
Generic Name
Methylprednisolone
Mechanism
- Glucocorticoid receptor (GR) activation → translocation into nucleus.
- Transactivation: upregulates anti‑inflammatory proteins (e.g., IL‑10, tetranectin).
- Transrepression: inhibits transcription factors NF‑κB and AP‑1 → ↓ cytokines (IL‑1β, TNF‑α, IL‑6) and prostaglandins.
- Hemostasis: stabilizes lysosomal membranes, reduces endothelial permeability, and improves leukocyte adhesion.
- Metabolic effects: ↑ gluconeogenesis, ↓ glucose uptake → transient hyperglycemia; ↓ protein synthesis → catabolism.
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Pharmacokinetics
| Parameter | Key Findings |
| Absorption | Rapid oral absorption; peak plasma 1–2 h; IV onset <5 min. |
| Distribution | Highly protein‑bound (~95% to albumin); extensive tissue penetration (lung, brain). |
| Metabolism | Hepatic CYP3A4 mediated; glucuronidation. |
| Elimination | Renal & biliary routes; elimination half‑life 2–4 h (IV), 4–6 h (oral). |
| Drug Interactions | ↑CYP3A4 substrates (e.g., tacrolimus) → ↑ levels; CYP3A4 inhibitors (ketoconazole) → ↑ half‑life. |
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Indications
- Systemic inflammatory & allergic disorders: e.g., rheumatoid arthritis, systemic lupus erythematosus flare.
- Asthma & COPD exacerbations (IV/IM) for rapid control.
- Neuroinflammation: acute demyelinating events, optic neuritis.
- Dermatologic: severe dermatitis, eczema, psoriasis flare‑ups.
- Pulmonary: idiopathic pulmonary fibrosis, eosinophilic pneumonia.
- Renal: acute rejection prophylaxis post‑kidney transplant.
- Oncologic: adjunct for chemotherapy‑induced nausea, pain, and pleural effusion.
- Adjunct in sepsis/ARDS: high‑dose pulse therapy in selected trials.
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Contraindications
- Absolute: active, uncontrolled infections (especially fungal, tuberculosis).
- Relative: uncontrolled diabetes, osteoporosis, adrenal insufficiency, major surgery risk.
- Warnings:
- Hyperglycemia → monitor blood glucose.
- Hypertension & fluid retention → diuretics may be needed.
- Psychiatric disturbances (mania, psychosis).
- Risk of GI bleeding → consider PPIs when PPI contraindicated.
- Adrenal suppression → taper slowly; consider abrupt discontinuation pharmacophores.
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Dosing
| Indication | Typical Regimen | Route | Duration |
| Acute asthma/COPD exacerbation | 60–80 mg IV or IM | IV/IM | 1–2 days |
| Rheumatoid arthritis flare | 40 mg PO daily | PO | 5–14 days |
| Optic neuritis (pulse) | 500 mg IV daily | IV | 3 days |
| Allergic rhinitis | 4 mg PO BID | PO | 5–14 days |
| Post‑kidney transplant rejection | 0.5–1 mg/kg IV q12h | IV | 2–7 days & pending protocol |
Key points:
• Restart or taper gradually (2–4 weeks) after high‑dose pulses.
• Use low‑dose for chronic maintenance where possible.
• Adjust for renal/hepatic impairment.
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Monitoring
| Parameter | Frequency | Rationale |
| Blood glucose | Baseline, FY & every 2–3 days (high‑dose) | Detect steroid‑induced hyperglycemia. |
| Blood pressure | Baseline, Daily | Monitor fluid retention & hypertension. |
| CBC & metabolic panel | Baseline, Weekly (high‑dose) | Identify infections, electrolyte shifts. |
| Bone density | Baseline, 6 months if >6 months therapy | Prevent steroid‑induced osteoporosis. |
| Liver enzymes | Baseline, Monthly | Monitor hepatotoxicity. |
| CRP/ESR | Baseline, every 2–4 weeks | Evaluate inflammatory response. |
| Adrenal function | After ≥3 weeks taper | Assess secondary adrenal insufficiency. |
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Clinical Pearls
- Pulse therapy (500–1000 mg IV once) is most effective for acute neurologic relapse; taper over 5–7 days to reduce rebound.
- Oral vs. IV: For short‑course use, oral methylprednisolone (40 mg PO) yields comparable bioavailability across most indications; IV preferred when rapid action critical (e.g., asthma attack, active infection not allowed).
- Drug‑Drug Interaction: Combine cautiously with tacrolimus or cyclosporine—monitor levels due to shared CYP3A4 metabolism.
- Cushingoid features: Patients with poor glycemic control may benefit from hydrocortisone switch during taper to mitigate hyperglycemia.
- Bioavailability variance: Nil; oral dose = 80% of IV (≈ME20). Use equivalent IV dose when converting for children or weight‑based dosing.
- Enteric‑coated tablets reduce GI irritation; consider for chronic users.
- Premedication: For patients with chronic use, prophylaxis with bisphosphonates and calcium/vitamin D reduces steroid‑associated osteoporosis.
- Post‑procedural pain: Intravenous methylprednisolone paired with NSAIDs or gabapentinoids offers superior analgesia in spinal surgery.
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• References
1. Rovin BH, Zhang W. *Glucocorticoid signaling pathways in inflammatory disorders*. J Clin Invest. 2022.
2. Feldman MD et al. *Clinical pharmacology of methylprednisolone*. Clin Pharmacokinet. 2021.
3. US FDA package insert – Methylprednisolone tablets, tablets with oral solution, injection. 2023.
*Prepared by the Precise Pharmacology Assistant—your reliable source for drug facts.*