Addison's disease

Question 1

Corticosteroids (Glucosteroids) systemic

Common indications

Answer 1

1. To treat allergic or inflammatory disorders, e.g. anaphylaxis, asthma
2. Suppression of autoimmune diseases 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. Hormonal replacement in adrenal insufficiency or hypopituitarism

Question 2

Corticosteroids (Glucosteroids) 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 tuble

Question 3

Corticosteroids (Glucosteroids) systemic

Important adverse effects

Answer 3

• Immunosuppression increases the risk and severity. of the infection and alters the host response
• Metabolic effects include diabetes 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
• HTN, hypokalaemia and oedema can result from mineralocorticoid actions
• Corticosteroid treatment suppresses pituitary adrenocorticotropic hormone (ACTH) secretion, switching

Question 4

Corticosteroids (Glucosteroids) systemic

Warnings

Answer 4

• corticosteroids should be prescribed with caution in people with infection and in children (suppresses growth)

Question 5

Corticosteroids (Glucosteroids) systemic

Important interactions

Answer 5

• Corticosteroids increase the risk of peptic ulceration and GI bleeds when used with NSAIDs and enhance hypokalaemia in patients taking B2-agonists, theophylline, loop or thiazide diuretics
• Their efficacy may be reduced by CYP P450 inducers (e.g. phenytoin, CBZ, rifampicin)
• Corticosteroids reduce the immune response to vaccines

Question 6

Corticosteroids (Glucosteroids) systemic

Communication

Answer 6

• Explain that treatment should suppress the underlying disease process that the patient will usually start to feel better within 1-2 days
• For patients who require prolonged treatment, warn them not to stop treatment suddenly, as this could make them very unwell
• Give them a steroid card to carry with them at all times and show if they need treatment
• Discuss the benefits and risks of steroids, including longer-term risks of osteoporosis, bone fractures and diabetes so that you patient can make an informed decision about taking treatment

Question 7

Corticosteroids (Glucosteroids) systemic

Monitoring

Answer 7

• Monitoring of efficacy will depend on the condition treated, e.g. peak flow recordings for asthma, blood inflammatory markers for inflammatory arthritis
• In prolonged treatment, monitor for adverse effects by, for example, measuring glucose and HbA1c or performing a dual-energy X-ray absorptiometry (DEXA) scan to look for osteoporosis