ENDO + REPRO: CORTICOSTEROIDS (GLUCOCORTICOIDS), SYSTEMIC

Question 1

CORTICOSTEROIDS, SYSTEMIC: INDICATIONS

Answer 1

• Tx allergic or inflammatory disorders, e.g. anaphylaxis, asthma
• Suppression of autoimmune disease, e.g. inflammatory bowel disease, inflammatory arthritis
• Tx of some cancers as part of chemotherapy or to reduce tumour-associated swelling
• Hormone replacement in adrenal insufficiency or hypopituitarism

Question 2

CORTICOSTEROIDS, SYSTEMIC: MOA

Answer 2

• 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.

Question 3

CORTICOSTEROIDS, SYSTEMIC: ADVERSE EFFECTS

Answer 3

Increases the risk and severity of infection

• Metabolic effects include DM + Osteoporosis
• Increased catabolism causes proximal muscle weakness, skin thinning with easy bruising and gastritis
• Mood and behavioural changes = insomnia, confusion, psychosis and suicidal ideas
• Hypertension, hypokalaemia and oedema can result from mineralocorticoid actions
• Adrenal atrophy
• Acute addisonian crisis
• Chronic glucocorticoid deficiency

Question 4

CORTICOSTEROIDS, SYSTEMIC: WARNINGS

Answer 4

Prescribe with caution in children and those who are infected (immunosupressed need to be careful to)

Question 5

CORTICOSTEROIDS, SYSTEMIC: INTERACTIONS

Answer 5

• Corticosteroids increase the risk of peptic ulceration and gastrointestinal bleeding when used with NSAIDs
• 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.

Question 6

CORTICOSTEROIDS, SYSTEMIC: EXAMPLES

Answer 6

• prednisolone
• hydrocortisone
• dexamethasone