prednisolone

**Class/Pharmacokinetics:** Synthetic glucocorticoid. Prednisone is a prodrug that the liver (11β-hydroxysteroid dehydrogenase type 1) converts to prednisolone. Prednisolone is given directly in severe liver disease, because those patients can't activate prednisone. Prednisolone is also the form used in ophthalmic drops and in pediatric liquid formulations. Relative potency (hydrocortisone = 1): prednisone/prednisolone ≈ 4, methylprednisolone ≈ 5, dexamethasone ≈ 25–30. Duration of action is intermediate (biologic half-life 12–36 h). Mineralocorticoid activity is minimal (hydrocortisone and fludrocortisone have the most).

**Mechanism:** It diffuses across the cell membrane and binds the cytosolic glucocorticoid receptor. The complex translocates to the nucleus and binds glucocorticoid response elements (GREs) to alter gene transcription. Effects: - ↑ lipocortin (annexin-1), which inhibits phospholipase A2. This blocks arachidonic acid release and so decreases prostaglandins and leukotrienes. - Inhibits NF-κB, which ↓ IL-1, IL-2, IL-6, TNF-α, and other cytokines. - ↓ T-cell proliferation and function, with ↓ eosinophils, lymphocytes, and basophils. - Neutrophilia from demargination and ↓ adhesion molecule expression, so neutrophils leave the marginated pool and enter circulation. - Induces lymphocyte apoptosis. This is why steroids treat lymphoid malignancies.

**Clinical uses:** - Autoimmune/rheumatologic: SLE, RA flares, polymyalgia rheumatica, giant cell arteritis (give immediately to prevent vision loss), vasculitides, sarcoidosis - Respiratory: asthma/COPD exacerbations - GI: IBD flares, autoimmune hepatitis - Renal: nephrotic syndrome (minimal change disease in children is steroid-responsive) - Hematologic: ITP, autoimmune hemolytic anemia, and lymphoma/leukemia regimens (e.g., R-CHOP) - Allergic and dermatologic disease; organ transplant immunosuppression - Neuro: Bell palsy and MS flares (often IV methylprednisolone) - Adrenal insufficiency replacement (hydrocortisone is preferred)

**Adverse effects (chronic use):** - Iatrogenic Cushing syndrome: moon facies, buffalo hump, central obesity, striae, and thin skin - Hyperglycemia/diabetes - Osteoporosis and avascular necrosis of the femoral head - Proximal myopathy - Peptic ulcer risk, especially with concurrent NSAIDs - HTN and fluid retention - Cataracts and glaucoma - Psychiatric effects: mood changes, psychosis, and insomnia - Immunosuppression with infection risk: PJP, reactivation of TB, and candidiasis - Growth suppression in children - Impaired wound healing - Leukocytosis (neutrophilia) with lymphopenia and eosinopenia

**HPA axis suppression:** Exogenous steroids suppress CRH and ACTH, causing adrenal atrophy (↓ ACTH, ↓ endogenous cortisol, with the zona glomerulosa mostly spared). Therapy longer than about 3 weeks requires a taper. Abrupt withdrawal can cause adrenal crisis (hypotension, hypoglycemia, hyponatremia, hyperkalemia is typically absent in secondary adrenal insufficiency). Patients on chronic steroids need "stress dosing" during surgery, sepsis, or major illness.

**Board pearls:** - The lab findings of steroid effect are ↑ neutrophils, ↓ lymphocytes, ↓ eosinophils, and hyperglycemia. - Prevent osteoporosis with calcium, vitamin D, and a bisphosphonate in long-term users. - Consider PJP prophylaxis (TMP-SMX) with prolonged high-dose therapy (e.g., ≥20 mg/day for ≥1 month). - Steroid-induced adrenal suppression is the most common cause of adrenal insufficiency overall. - Dexamethasone has no mineralocorticoid activity and is the longest-acting. Prednisolone is intermediate. - Inhaled forms (e.g., budesonide, fluticasone) reduce systemic effects but can cause oral candidiasis.