Question
A 60 year old lady is suffering from rheumatoid arthritis and has been prescribed
prednisolone. Answer the following:
- (a) What is the mechanism of action of glucocorticoids. 2 mark(s)
- (b) Name two glucocorticoids which have no mineralocorticoid activity 1 mark(s)
- (c) Enumerate the adverse effects that you expect in this patient 3 mark(s)
Q16 marksEssays
Answer
(a) Mechanism of action of glucocorticoids
- Act on intracellular glucocorticoid receptors (cytoplasmic)
- Drug-receptor complex translocates to the nucleus and binds glucocorticoid response elements (GRE) on DNA
- Modulates gene transcription:
- Induces synthesis of anti-inflammatory proteins (e.g., lipocortin-1/annexin A1, which inhibits phospholipase A2 → reduces arachidonic acid release → reduces prostaglandin and leukotriene synthesis)
- Represses transcription of pro-inflammatory genes (cytokines, COX-2, adhesion molecules) via inhibition of NF-κB and AP-1
- Onset of action is delayed (hours) as it depends on new protein synthesis
(b) Glucocorticoids with no mineralocorticoid activity
- Betamethasone
- Dexamethasone
(c) Adverse effects expected with prednisolone therapy in this patient
- Cushingoid features — moon facies, buffalo hump, central obesity
- Osteoporosis and increased fracture risk (particularly relevant given age)
- Hyperglycaemia / precipitation of diabetes
- Hypertension and fluid retention
- Increased susceptibility to infections (immunosuppression)
- Peptic ulceration
- Muscle wasting/myopathy
- Skin thinning, poor wound healing, easy bruising
- Adrenal suppression (HPA axis suppression) — risk with abrupt withdrawal
- Cataract and glaucoma (long-term use)
- Psychiatric disturbances (mood changes, insomnia)
- 1Corticosteroids
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