Corticosteroids - Prednisolone

Question 1

What are corticosteroids like prednisolone used for?

Answer 1

1) allergic or inflammatory disorders e.g. anaphylaxis / asthma
2) suppression of autoimmune disease e.g. IBD
3) cancer (as part of chemo to reduce tumour swelling)
4) hormone replacement in adrenal insufficiency or hypopituitarism

Question 2

What is the mechanism of action of prednisolone?

Answer 2

• Corticosteroids UP regulate anti-inflammatory genes and DOWN regulate pro-inflammatory genes like cytokines, TNF-a
• metabolic effect increase gluconeogenses.
• mineralcorticoid effects —> Na+ and water retention / K+ elimination.

How they work in the cell:

• Corticosteroids bind to cytosolic glucocorticoid receptors.
• this then stimulates activation of glucocorticoid response elements in the nucleus.
• this regulates gene expression.

Question 3

What are the side effects of prednisolone?

Answer 3

1) immunosuppression
2) Metabolic effects (diabetes and osteoporosis)
3) proximal muscle weakness,
4) Skin thinning/bruising
5) gastritis
6) Mood / behaviour change = insomnia, confusion, psychosis, suicidal ideas
7) hypertension, oedema and hyperkalaemia - due to mineralcorticoid actions
8) adrenal atrophy

Question 4

What is the side effect of prolonged corticosteroid treatment?

Answer 4

• Adrenal atrophy

Question 5

What is the risk of sudden withdrawal of long term corticosteroids?

Answer 5

Addisonian crisis

(malaise, fatigue, Naus/vom, abdo pain, low grade fever, muscle pain —-> dehydration —->hypotension —> hypovolaemic shock

Question 6

When long term corticosteroids are withdrawn slowly symptoms of chronic glucocorticoid deficiency can occur - what are these symptoms?

Answer 6

• fatigue
• weight loss
• athralgia

Question 7

Who should corticosteroids be used in caution with?

Answer 7

• infection

- children

Question 8

What are the drug interactions of corticosteroids?

Answer 8

1) NSAIDs (combination increases risk of peptic ulcer and GI bleed —> PPI needed)
2) enhance hypokalaemia: Beta 2 agonists, theophylline, loop diuretics, thiazide diuretics

3) Efficacy of corticosteroids reduced by cytochrome P450 inducers e.g.
- phenytoin
- carbamezapine
- rifampicin

4) corticosteroids reduce immune response to vaccines

Question 9

What drugs enhance the hypokalaemic effect of corticosteroids?

Answer 9

• beta 2 agonist
• loop diuretics (furosemide)
• thiazide diuretics (bendroflumethiazide)

Question 10

What drugs reduce the efficacy of corticosteroids?

Answer 10

Cytochrome P450 enzyme inducers:

• Phenytoin
• carbamezapine
• rifampicin

Question 11

What is the dose of prednisolone for acute asthma?

Answer 11

40 mg orally daily

Question 12

why should once daily corticosteroid treatment be taken in the morning?

Answer 12

to mimic the natural circadian rhythm and reduce insomnia