Glucocorticoids

Glucocorticoids are synthetic and natural steroids acting on the glucocorticoid receptor. They are used as replacement in adrenal insufficiency and congenital adrenal hyperplasia, and in pharmacological doses for anti-inflammatory, immunosuppressive, anti-oedema and antiemetic effects.

Mechanism. The ligand-receptor complex enters the nucleus and alters gene expression: transactivation of anti-inflammatory genes and repression of NF-kB and AP-1 driven cytokine genes. Effects include reduced lymphocyte and eosinophil function, stabilised membranes, reduced vascular permeability, raised hepatic glucose output and protein catabolism.

Pharmacokinetics. Oral bioavailability is high. Prednisone is a prodrug converted by the liver to prednisolone. Biological half-life: hydrocortisone 8 to 12 hours, prednisolone 12 to 36 hours, dexamethasone 36 to 54 hours.

Choice. Hydrocortisone for replacement and adrenal crisis. Prednisolone for most oral anti-inflammatory use. Dexamethasone for cerebral oedema, meningitis, croup, chemotherapy-induced vomiting and antenatal lung maturation (with betamethasone). Methylprednisolone for pulse therapy.

• Primary adrenal insufficiency replacement: hydrocortisone 15 to 25 mg daily in 2 to 3 divided doses (for example 10 mg on waking, 5 mg at midday, 5 mg mid-afternoon), with fludrocortisone. Double or triple the dose during fever, and give parenterally if vomiting.
• Adrenal crisis: hydrocortisone 100 mg intravenously or intramuscularly at once, then 50 mg every 6 hours or 200 mg over 24 hours by infusion, with 1 litre of 0.9% sodium chloride in the first hour. Do not delay for tests.
• Asthma exacerbation: prednisolone 40 to 50 mg daily for 5 days. COPD exacerbation: 30 to 40 mg daily for 5 days.
• Bacterial meningitis: dexamethasone 0.15 mg/kg (10 mg in adults) every 6 hours for 4 days, started before or with the first antibiotic dose.
• Pneumocystis pneumonia with hypoxia: prednisolone 40 mg twice daily for 5 days, 40 mg daily for 5 days, then 20 mg daily for 11 days.
• Antenatal lung maturation (24 to 34 weeks): betamethasone 12 mg intramuscularly, 2 doses 24 hours apart, or dexamethasone 6 mg intramuscularly every 12 hours for 4 doses.
• Croup: dexamethasone 0.15 mg/kg once.
• Giant cell arteritis: prednisolone 40 to 60 mg daily; add intravenous methylprednisolone 500 mg to 1 g daily for 3 days with visual loss.
• Withdrawal: after more than 3 weeks at over 5 mg prednisolone daily, or any course over 40 mg daily for more than 1 week, taper to avoid adrenal insufficiency.

Special groups. Pregnancy: prednisolone and hydrocortisone are largely inactivated by the placenta; dexamethasone and betamethasone cross it and are used deliberately for foetal effects. Breastfeeding: compatible; for prednisolone over 40 mg daily, wait 4 hours after the dose. Children: growth suppression with long courses; use alternate day or lowest dose. Older adults: bone, glucose and psychiatric effects. Kidney impairment: no adjustment.

Liver impairment: use prednisolone rather than prednisone. Regional: before prolonged high-dose steroid in people from Strongyloides-endemic areas, treat empirically with ivermectin 200 micrograms/kg as a single dose to prevent hyperinfection. Screen for latent tuberculosis in high-risk patients and for hepatitis B. Steroids can worsen Kaposi sarcoma.

Adverse effects. Hyperglycaemia, weight gain and Cushingoid features, hypertension, hypokalaemia, osteoporosis and avascular necrosis, myopathy, peptic ulcer (with NSAIDs), infection, adrenal suppression, mood disorder and psychosis, cataract and glaucoma, and skin thinning.

Bone protection. For 3 months or more of prednisolone 7.5 mg daily or equivalent, give calcium and vitamin D, and consider a bisphosphonate in patients over 40 or with fractures.

Interactions. Rifampicin, phenytoin, carbamazepine and phenobarbital lower exposure (raise the dose). Ketoconazole, itraconazole, clarithromycin and ritonavir raise exposure, and with ritonavir cause Cushing syndrome even from inhaled or injected steroid. Diuretics and amphotericin add hypokalaemia. NSAIDs raise ulcer risk. Live vaccines are avoided on high doses.

Monitoring. Blood pressure, glucose, potassium, weight, bone health, eyes, mood, and growth in children. Steroid alert card for patients on long-term therapy.

Referral and escalation. Adrenal crisis, steroid psychosis, suspected tuberculosis or strongyloidiasis, and difficult tapering.