Corticosteroids — Mechanism, Relative Potency, Adverse Effects, Tapering and Antenatal Use

Corticosteroids are synthetic analogues of the steroid hormones made by the adrenal cortex. They include glucocorticoids — which act mainly on metabolism and have anti-inflammatory, immunosuppressive and vasoconstrictive effects — and mineralocorticoids, which regulate salt and water balance by acting on ion transport in the renal tubular epithelium. In everyday use the word 'corticosteroid' usually means the glucocorticoid effect.

Each synthetic steroid has a different mix of glucocorticoid and mineralocorticoid activity and a different duration of action. Exams classify them by duration: short-acting (hydrocortisone, cortisone), intermediate-acting (prednisone, prednisolone, methylprednisolone, triamcinolone) and long-acting (dexamethasone, betamethasone). Fludrocortisone stands apart as the steroid used for its mineralocorticoid action.

They are given at physiological doses as replacement (adrenal insufficiency, congenital adrenal hyperplasia) and at supraphysiological doses for anti-inflammatory and immunosuppressive effects. Routes include oral, parenteral, inhaled, topical, intra-articular, intralesional and rectal; StatPearls advises non-systemic routes whenever possible to limit systemic exposure.

Corticosteroids have genomic and non-genomic actions. The genomic action produces most of the anti-inflammatory and immunosuppressive effect and is mediated by the glucocorticoid receptor, which sits in the cytoplasm. Once the steroid binds, the receptor complex moves rapidly into the nucleus, where it alters gene transcription — switching off expression of inflammatory genes in leucocytes and structural cells such as epithelium.

• Net genomic result: fewer pro-inflammatory cytokines, chemokines, cell adhesion molecules and inflammatory enzymes.
• Non-genomic action: faster (seconds to minutes), through the intracellular or a membrane-bound receptor — including inhibition of phospholipase A2, which limits release of arachidonic acid and therefore downstream inflammatory mediators.
• At high concentrations: suppression of B- and T-cell production — the basis of their immunosuppressive use.
• Other effects: protein and carbohydrate metabolism, water and electrolyte handling, central nervous system and blood-cell effects.

Potency is expressed relative to hydrocortisone = 1. The table below follows the NICE-derived table reproduced by Liu and colleagues (oral or IV doses); intramuscular or intra-ocular potency can differ considerably.

• Hydrocortisone — its relatively high mineralocorticoid activity makes it suitable for adrenal insufficiency replacement.
• Prednisolone — high glucocorticoid activity; the usual oral drug for long-term anti-inflammatory and immunosuppressive treatment.
• Dexamethasone — used especially when water retention is undesirable (minimal mineralocorticoid effect); usually kept for short-term use in severe acute conditions because of its high potency and long action.
• Fludrocortisone — used for aldosterone replacement. A mineralocorticoid effect roughly equal to 0.1 mg fludrocortisone needs about 50 mg prednisolone or 20 mg hydrocortisone.

Adverse effects depend on the average dose and the cumulative duration; StatPearls notes they occur in up to 90% of patients who take steroids for more than 60 days. Synthetic steroids (prednisone, methylprednisolone, dexamethasone, betamethasone) cause more Cushingoid change and HPA suppression with little mineralocorticoid effect.

• Contraindications (StatPearls): systemic fungal infection, live vaccines with immunosuppressive doses, uncontrolled diabetes or hypertension, glaucoma, osteoporosis, joint infection, herpes simplex keratitis and varicella; relative — peptic ulcer, heart failure and uncontrolled infections.
• Live vaccines: delay for 3 months after stopping immunosuppressive doses (prednisolone 40 mg/day or more for more than 7 days).
• Prevention: lowest effective dose for the shortest time, single morning or alternate-day dosing, calcium and vitamin D, bone density checks, a PPI if also on NSAIDs, and a steroid treatment card.

Exogenous steroids suppress the hypothalamic–pituitary–adrenal axis, so the adrenal cortex atrophies and cannot produce cortisol on demand. Sudden withdrawal after a long course can cause adrenal insufficiency and flare of the underlying disease. Long-term high-dose therapy can keep the HPA axis suppressed for 9–12 months after withdrawal.

1. Reduce by 2.5–5 mg every 3–7 days until a physiological dose (about 5–7.5 mg prednisone/day) is reached; go slower if relapse is a concern.
2. Switch to hydrocortisone 20 mg once daily in the morning.
3. Reduce hydrocortisone by 2.5 mg over weeks to months.
4. Check an early-morning (8 am) cortisol: below 85 nmol/L means the axis has not recovered; above 500 nmol/L means it is intact and steroids can stop.

An adrenal crisis is acute, life-threatening adrenal insufficiency. Gastrointestinal and flu-like illnesses are the commonest triggers; others include surgery, trauma, childbirth, non-adherence and abrupt stopping of long-term steroids. Hyponatraemia, hyperkalaemia or hypoglycaemia with hypotension should raise suspicion. Treatment is not delayed for test results.

• Hydrocortisone 100 mg IV or IM immediately, then 200 mg over the next 24 hours (for example 50 mg every 6 hours).
• IV fluid resuscitation, correction of glucose and electrolytes, and a search for the trigger.
• Patients should carry a steroid card and keep an emergency kit (hydrocortisone 100 mg or dexamethasone 4 mg injection).
• Sick-day rules: for a minor illness, increase hydrocortisone to 2–3 times the usual dose for 2–3 days; more for major illness.

Antenatal corticosteroids speed up fetal lung maturation and reduce respiratory distress syndrome and death in preterm babies. Betamethasone and dexamethasone are used because, as fluorinated steroids, they cross the placenta easily — they are not a substrate for placental 11β-hydroxysteroid dehydrogenase, which inactivates cortisol.

• Window: a single course for imminent preterm birth from 24+0 to 34+0 weeks is included in guidelines worldwide.
• WHO 2022 conditions: gestational age can be accurately assessed, preterm birth is imminent, no clinical evidence of maternal infection, adequate childbirth care, and the preterm newborn can receive adequate care.
• Below 34 weeks there is compelling evidence of reduced perinatal and neonatal mortality and respiratory morbidity; after 34 weeks there is no mortality difference, a modest fall in respiratory morbidity and more neonatal hypoglycaemia (WHO).
• Head-to-head (ASTEROID trial), betamethasone and dexamethasone gave similar outcomes for death or neurosensory disability at 2 years.
• Pre-eclampsia: NICE NG133 offers a course if birth is likely within 7 days — but not dexamethasone or betamethasone to treat HELLP syndrome.

• Potency ranking — most potent glucocorticoid (dexamethasone/betamethasone) or highest mineralocorticoid activity (fludrocortisone).
• Drug for a situation — when salt and water retention must be avoided (dexamethasone); adrenal insufficiency replacement (hydrocortisone ± fludrocortisone); fetal lung maturity (betamethasone/dexamethasone).
• Adverse effect identification — proximal myopathy, cataract and raised intraocular pressure, avascular necrosis of the femoral head, steroid-induced diabetes.
• Withdrawal — a patient on long-term prednisolone who stops suddenly and presents with hypotension and hypoglycaemia → adrenal crisis → IV hydrocortisone 100 mg.
• Peri-operative cover — stress-dose hydrocortisone for a patient on chronic steroids.

For past papers, see the NEET PG pharmacology PYQs. Steroids also come up in hypersensitivity reactions and alongside antihypertensive drugs, where steroid-induced hypertension and fluid retention are common distractors.