Corticosteroids (glucocorticoids), systemic

Key examples

• Prednisolone
• Hydrocortisone
• Dexamethasone

 

Common indications

1. To treat allergic or inflammatory disorders, e.g. anaphylaxis, asthma.
2. Suppression of autoimmune disease, e.g. inflammatory bowel disease, inflammatory arthritis.
3. In the treatment of some cancers as part of chemotherapy or to reduce tumour-associated swelling.
4. Hormone replacement in adrenal insufficiency or hypopituitarism.

 

Mechanisms of action

• These corticosteroids exert mainly glucocorticoid effects. 
• They bind to cytosolic glucocorticoid receptors, which then translocate to the nucleus and bind to glucocorticoid-response elements, which regulate gene expression. 
• Corticosteroids are most commonly prescribed to modify the immune response. 
• They upregulate anti-inflammatory genes and downregulate pro-inflammatory genes (e.g. cytokines, tumour necrosis factor alpha). 
• Direct actions on inflammatory cells include suppression of circulating monocytes and eosinophils. 
• Their metabolic effects include increased gluconeogenesis from increased circulating amino and fatty acids, released by catabolism (breakdown) of muscle and fat. 
• These drugs also have mineralocorticoid effects, stimulating Na+ and water retention and K+ excretion in the renal tubule.

 

Important adverse effects

• Immunosuppression increases the risk and severity of infection and alters the host response. 
• Metabolic effects include diabetes mellitus and osteoporosis. Increased catabolism causes proximal muscle weakness, skin thinning with easy bruising and gastritis. 
• Mood and behavioural changes include insomnia, confusion, psychosis and suicidal ideas. 
• Hypertension, hypokalaemia and oedema can result from mineralocorticoid actions.
• Corticosteroid treatment suppresses pituitary adrenocorticotropic hormone (ACTH) secretion, switching off the stimulus for normal adrenal cortisol production. In prolonged treatment, this causes adrenal atrophy, preventing endogenous cortisol secretion. If corticosteroids are withdrawn suddenly, an acute Addisonian crisis with cardiovascular collapse may occur. Slow withdrawal is required to allow recovery of adrenal function. 
• Symptoms of chronic glucocorticoid deficiency that occur during treatment withdrawal include fatigue, weight loss and arthralgia.

 

Warnings

• Corticosteroids should be prescribed with caution in people with infection and in children (in whom they can suppress growth).

 

Important interactions

• Corticosteroids increase the risk of peptic ulceration and gastrointestinal bleeding when used with NSAIDs and enhance hypokalaemia in patients taking β2-agonists, theophylline, loop or thiazide diuretics. 
• Their efficacy may be reduced by cytochrome P450 inducers (e.g. phenytoin, carbamazepine, rifampicin). 
• Corticosteroids reduce the immune response to vaccines.