Corticosteroids

Indications

Corticosteroids have varying indications with varying doses. 

• Glucocorticoid replacement therapy in adrenal insufficiency e.g. hydrocortisone
• Mineralocorticoid replacement therapy in Addison’s disease e.g. fludrocortisone
• Anti-inflammatory: exacerbation of COPD or asthma, allergic reaction
• Immunosuppressive: autoimmune conditions (e.g. inflammatory bowel disease), acute transplant rejection, inflammatory arthritis 
• Postural hypotension e.g. fludrocortisone
• Treatment of some cancers or to reduce tumour associated swelling 

Prednisolone is usually the drug of choice for its anti-inflammatory and immunosuppressive effects. Dexamethasone is often used for its anti-inflammatory or immunosuppressive effects, when water retention is undesirable. 

Mechanism of Action

In naturally occurring steroids, mineralocorticoid and glucocorticoid actions are not completely separate and overlapping activity occurs.  

Endogenous glucocorticoids such as cortisol regulate metabolic, anti-inflammatory and immunosuppressive actions. Endogenous glucocorticoids are synthesised and released in a pulsatile way into the blood, peaking in the morning. Glucocorticoids bind to intracellular receptors, dimerise and migrate to the nucleus of the cell, where gene transcription is modified (approximately 1–2% of genes are regulated by glucocorticoid receptor activation), leading to anti-inflammatory and immunomodulatory effects. Some effects are listed below: 

• Reduced activation of neutrophils, macrophages, mast cells and T-helper cells
• Reduced expression of cyclo-oxygenase 2 leading to decreased production of prostanoids 
• Down-regulation of proinflammatory cytokine generation 
• Reduced histamine release 
• Increased gluconeogenesis from amino acids and fatty acids 

Endogenous mineralocorticoids, such as aldosterone, regulate fluid and electrolyte balance in the body, release is regulated by the renin-angiotensin system. 

Aldosterone, alongside exogenous mineralocorticoids bind to the mineralocorticoid receptor which is present in the kidney, colon and bladder. This leads to an increase in sodium channels in the renal tubular cell, Na+-K+-ATPase molecules in the basolateral membrane, leading to increased potassium excretion and sodium and water reabsorption. With exogenous corticosteroids, this effect is greatest with fludrocortisone and hydrocortisone, and minimal with dexamethasone. 

Pharmacological Properties

Activity

Fludrocortisone is the drug of choice for mineralocorticoid activity, such as in postural hypotension. Prednisolone, hydrocortisone (cortisol), dexamethasone and fludrocortisone all bind to the glucocorticoid receptor and elicit glucocorticoid effects. Hydrocortisone also exhibits high mineralocorticoid activity, whereas with dexamethasone this is minimal. 

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Fig 1: Corticotropin-releasing factor (CRF) is released from the hypothalamus which regulates adrenocorticotropic hormone (ACTH) secretion, which leads to synthesis of glucocorticoids in the adrenal gland. All steroid hormones are synthesised from cholesterol. 

Conversion

Corticosteroid doses are not equivalent, the table below demonstrates the approximate equivalence of different steroids.

By TeachMeSeries Ltd (2026)

Fig 2: Glucocorticoid equivalence

Contraindications

• Corticosteroid therapy is contraindicated in people with acute infections which are uncontrolled by appropriate antibiotics 
• Live vaccines should generally be avoided in patients receiving high-dose immunosuppressive corticosteroid therapy. 

Cautions and Adverse Effects

Glucocorticoid Mediated Adverse Effects

Immunosuppression

Due to the mechanism of action of glucocorticoids, there is a higher risk of opportunistic infection such as oesophageal candidiasis. 

Metabolic

Glucocorticoids reduce the uptake and utilisation of glucose and increase gluconeogenesis (synthesis of glucose), which can lead to hyperglycaemia. Corticosteroids can also lead to weight gain, increased appetite and increased cholesterol levels. 

Central serous chorioretinopathy (CSCR)

MHRA warning issued in 2017 for CSCR with systemic corticosteroids, therefore patients should be advised to report any blurred vision or visual disturbances.

Endocrine

Cushing’s Syndrome

This is usually reversible on withdrawal of corticosteroid treatment 

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Fig 3: Cushing’s syndrome signs and symptoms

Adrenal Suppression

In patients on regular high dose glucocorticoids, adrenal suppression can occur, due to suppression of the patient’s ability to synthesise corticosteroids. This is due to inhibition of secretion of endogenous glucocorticoids due to activation of the negative feedback effect on the secretion of CRF and ACTH. This can ultimately lead to atrophy of the adrenal cortex. 

In the UK, patients should be issued with steroid emergency cards (red) if they have adrenal insufficiency and steroid dependence, as they are at risk of adrenal crises during illness and surgery. The suppressive action of corticosteroids on cortisol secretion is less when corticosteroids are given in the morning, as this mimics the natural circadian rhythm.

Steroid treatment cards (blue) should also be issued to the following patient groups

• Oral corticosteroid treatment lasting longer than 3 weeks.
• More than four short courses of oral corticosteroids within a 12-month period, where deemed clinically necessary by the prescriber or pharmacist.
• Concurrent use of oral corticosteroids with other glucocorticoid preparations, such as inhaled or topical corticosteroids.
• Concomitant use of oral corticosteroids with a cytochrome P450 3A4 (CYP3A4) inhibitor, including ritonavir, itraconazole, or ketoconazole.

Gastrointestinal disorders

• Increased risk of peptic ulcer disease due to impaired wound healing
• Can also cause nausea, diarrhoea, dyspepsia and abdominal distension

Psychiatric reactions such as insomnia, anxiety and depression

Long term use can lead to depression, whereas short term use can cause euphoria and psychosis. Corticosteroids should be taken in the morning to reduce the risk of insomnia. 

Musculoskeletal and connective tissue

• Inhibition of growth in children; more likely with long term use (> 6 months)
• Increased risk of osteoporosis due to the risk of hypocalcaemia and effect on phosphate metabolism and collagen turnover, reduced osteoblast function and increased osteoclasts, leading to a decrease in bone density and increase in risk of fractures. 
• Avascular necrosis of the head of the femur can also occur due to an effect on the blood supply to the bone. 
• Tissue wasting can occur due to a reduction in protein synthesis and an increase in protein breakdown in muscle.
• Tendon rupture 

Mineralocorticoid Mediated Adverse Effects

Mineralocorticoid adverse effects can also be caused by primary or secondary hyperaldosteronism. Adverse effects include the following:

• Hypertension
• Sodium and water retention
• Hypokalaemia 
• Hypocalcaemia – due to a reduction of calcium absorption in the gastrointestinal tract and increased renal excretion 

Due to these effects, patients requiring treatment with corticosteroids who also have congestive heart failure should be treated with caution as their symptoms may worsen. 

Monitoring

Patients requiring long term therapy with corticosteroids should have the following monitoring undertaken (as baseline then regular intervals during treatment):

• HbA1c
• Blood pressure
• Body weight and body mass index (BMI)
• Triglycerides
• Potassium
• Eye examination (for glaucoma and cataract)
• Consider dual-energy X-ray absorptiometry (DEXA) scan to measure bone density if there is risk of osteoporosis 

Withdrawal

Certain patient groups will require gradual tapering of steroid doses if the disease is unlikely to relapse. Abrupt withdrawal should be avoided in these patient groups due to the risk of  suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Morning dosing and alternate-day therapy (where clinically appropriate) may reduce this risk.

• Received prednisolone at a dose greater than 40 mg daily (or equivalent) for more than 1 week, 2 mg/kg daily for 1 week, or 1 mg/kg daily for 1 month.
• Taking repeated evening doses of corticosteroids
• Received corticosteroid therapy for more than 4 weeks if aged 16 years or older, or for more than 3 weeks if under 16 years of age.
• Recently undergone repeated courses of corticosteroids, particularly if treatment lasted longer than 3 weeks (for example, for acute asthma exacerbations).
• Taken a short course of corticosteroids within 1 year of discontinuing long-term corticosteroid therapy.
• Additional risk factors for adrenal suppression, such as excessive alcohol consumption or significant physiological stress (for example, infection, trauma, or surgery).

Interactions

Spironolactone is a competitive aldosterone antagonist and counteracts the effects of fludrocortisone. Therefore, when used together, the two medicines have opposing pharmacological effects.

Tendon rupture risk

Corticosteroids given alongside quinolone antibiotics increase the risk of tendon rupture and tendinitis 

Vaccines

Live vaccines should be avoided in patients on high dose immunosuppressant therapy such as corticosteroids, if required they should be given at least 4 weeks before commencing corticosteroid treatment or 3 months after stopping. 

CYP450 mediated interactions

Efficacy may be reduced by CYP450 inducers such as phenytoin and carbamazepine and exposure increased by CYP450 inhibitors such as ritonavir, itraconazole and ketoconazole.  

Hypokalaemia

Increased risk of hypokalaemia when given alongside the following:

• Loop diuretics 
• Thiazide and thiazide-like diuretics 
• Theophylline
• Laxatives
• Amphotericin B 
• Insulin

There is an increased risk of digoxin toxicity if hypokalaemia is present, therefore use of corticosteroids alongside digoxin should be undertaken with appropriate monitoring in place. 

Peptic ulcer risk

Drugs with glucocorticoid activity increase the risk of peptic ulcers therefore should be used with caution with other medications that can cause this effect such as NSAIDs, SSRIs, anticoagulants or antiplatelets. Stomach protection (most commonly prescribed as a Proton Pump Inhibitor) can be considered alongside corticosteroid treatment in high risk patients.

References

1. Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan DJ. Rang & Dale’s Pharmacology. 9th ed. London: Elsevier; 2019.
2. Hitchings BSc, M., Lonsdale, D., Burrage, D., Baker, E. (2022). The Top 100 Drugs – E-Book. Netherlands: El
3. Corticosteroids, general use | Treatment summaries | BNF | NICE Accessed 9/7/26
4. Scenario: Corticosteroids | Management | Corticosteroids – oral | CKS | NICE  Accessed 10/7/26