prednisone

Brand: Deltasone, Rayos

Prototype Drug
Drug Class: corticosteroid
Drug Family: corticosteroid
Subclass: synthetic glucocorticoid (intermediate-acting)
Organ Systems: endocrineimmunology

Mechanism of Action

Prodrug converted to active prednisolone by 11-beta-HSD1; activates cytosolic glucocorticoid receptors, translocating to nucleus to transactivate anti-inflammatory genes (lipocortin-1) and transrepress pro-inflammatory transcription factors (NF-kB, AP-1); reduces synthesis of prostaglandins, leukotrienes, and cytokines.

glucocorticoid receptor (GR)

Indications

  • autoimmune diseases (rheumatoid arthritis, lupus, IBD, vasculitis)
  • allergic reactions and anaphylaxis (adjunct)
  • asthma exacerbations
  • COPD exacerbations
  • adrenal insufficiency (with fludrocortisone)
  • organ transplant rejection prophylaxis
  • anti-emetic (CINV — high-dose)
  • cerebral edema (IV dexamethasone preferred for brain tumors)

Contraindications

  • systemic fungal infections (without concurrent antifungal therapy)
  • live vaccines in immunocompromised doses

Adverse Effects

Common

  • hyperglycemia
  • weight gain / increased appetite
  • insomnia
  • mood changes (euphoria, anxiety, depression)
  • GI irritation
  • fluid retention / hypertension

Serious

  • HPA axis suppression (adrenal insufficiency on abrupt withdrawal)
  • osteoporosis (long-term)
  • Cushing's syndrome (iatrogenic)
  • immunosuppression / opportunistic infections
  • myopathy
  • avascular necrosis of the femoral head
  • cataracts and glaucoma (long-term)

Pharmacokinetics (ADME)

Absorption Well absorbed orally; converted to prednisolone in liver
Distribution Widely distributed; protein binding ~70%; crosses placenta, BBB
Metabolism Converted to prednisolone by hepatic 11-beta-HSD1; further metabolism by CYP3A4
Excretion Renal
Half-life Biological half-life 18–36 hours (HPA suppression); plasma half-life ~3–4 hours (prednisolone)
Onset 1–2 hours
Peak 2 hours
Duration 12–36 hours (biological effect)
Protein Binding 70%
Vd ~1 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
CYP3A4 inducers (rifampin, phenytoin, carbamazepine) reduce prednisolone levels by 50–60%; may require dose doubling major
NSAIDs additive GI irritation and peptic ulcer risk moderate
live vaccines immunosuppression increases risk of vaccine-strain dissemination; avoid with doses >20 mg/day for >14 days major

Nursing Considerations

  1. Administer with food to reduce GI irritation; take in the morning to mimic physiologic cortisol peak and minimize insomnia and HPA suppression
  2. Never abruptly discontinue after more than 2 weeks of therapy — taper dose gradually to allow HPA axis recovery; warn patient about signs of adrenal insufficiency (fatigue, nausea, dizziness) during tapering
  3. Monitor blood glucose, blood pressure, weight, electrolytes, and mood; screen for osteoporosis with DEXA scan for long-term therapy; prescribe calcium and vitamin D with any chronic steroid course
  4. Patient education: take with food; don't abruptly stop; avoid sick contacts; report any signs of infection; stress dosing may be needed during major illness or surgery

Clinical Pearls

  • Prednisone is a prodrug that requires hepatic conversion to prednisolone — in severe hepatic disease, prednisolone should be used directly to ensure reliable drug activation
  • The Beers-like maxim of 'lowest dose for shortest duration' applies strictly to glucocorticoids — even short burst courses (1 week of 40 mg) cause measurable bone density loss and insulin resistance; these effects accumulate with repeated courses

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required