Corticosteroids

Question 1

Name the 5 examples of corticosteroids on the PPE drugs list

Answer 1

• Fludrocortisone
• Hydrocortisone (oral or topical)
• Betamethasone (topical)
• Prednisolone
• Dexamethasone

Question 2

From which chemical is cortisol produced?

Where does this conversion occur?

Answer 2

Cholesterol

Adrenal cortex

Question 3

Give some general physiological actions of glucocorticoids

Answer 3

Stimulate:

• Glycogenolysis
• Gluconeogenesis
• Proteolysis
• Redistribution of fat

Question 4

Give some features of a low glucocorticoid state

Answer 4

• Hypoglycaemia
• Weight loss
• Nausea
• Hypotension

Question 5

Give some features of a high glucocorticoid state

Answer 5

• Hyperglycaemia
• Weight gain
• Increased appetite
• Hypertension

Question 6

What is steroid receptor homology?

Answer 6

Similar structure of glucocorticoids mean that in excess they will also bind to mineralocorticoids - exert some mineralocorticoid action such as increased Na+ reabsorption

Question 7

Which pharmacological corticosteroid is good for replacing aldosterone due to its large effect at mineralocorticoid receptors compared to GC receptors?

Answer 7

Fludrocortisone

Question 8

Briefly outline the mechanism of action of corticosteroids at the molecular/cellular level

Answer 8

• Cross cell membrane as lipophilic
• Bind to cytosolic receptors - complex translocates to nucleus where it binds with glucocorticoid response element
• Bound GRE then modulates transcription of various genes - both stim and inhib:
• Trans-activation = stimulation of protein synthesis of anti-inflam proteins
• Trans-repression = inhibition of protein synth of inflam proteins

Question 9

Outline corticosteroids’ mechanism of action in terms of effects on the immune system

Answer 9

• Inhibition of B and T cell responses
• Inhibition of nuclear factor kappa B
• Reduced transcription of cytokines

Question 10

Give some examples of use of corticosteroids

Answer 10

• Inflammatory disease
• Immunosuppression
• Adrenal insufficiency

Question 11

What is Dexamethasone used for?

Answer 11

Diagnosis of Cushing’s syndrome

Question 12

How could corticosteroids be useful for pregnant women?

Answer 12

Reduce risk of respiratory distress syndrome in preterm babies - stimulate development of type II pneumocytes - surfactant production

Question 13

List some ADRs of corticosteroids

Answer 13

• Osteoporosis
• Peptic ulcers
• Increased risk of infection
• Impaired growth
• Cushingoid features
• Cross-over with MC - fluid retention

Question 14

Why shouldn’t you suddenly stop long-term corticosteroids?

Answer 14

Adrenal suppression - can’t make own cortisol - can have hypoadrenal crisis