Pharmacology: Glucocorticoids

Question 1

Describe the mechanism of action of glucocortocoids

Answer 1

1. Glucocorticoids bind to the ligand binding domain of the glucocorticoid receptor
2. As a dimer, the GC-bound GR activates transcription while it represses transcription as a monomer

• If glucocorticoid response element DNA sequence favours GR dimer formation → target gene expression induced
• If glucocorticoid response element DNA sequence suppresses GR dimer formation → target gene expression repressed

Question 2

What medication can you co-administer alongside glucocorticoids to inhibit glucocorticoid-induced delay in wound healing and glucocorticoid-induced skin atrophy?

Answer 2

Mineralocorticoids - cutaneous adverse effects of glucocorticoids may be partially triggered by glucocorticoids acting on the mineralocorticoid receptor

Question 3

Describe the clinical features of a patient with increased circulating cortisol and ATCH due to a mutation/polymorphism

Answer 3

May have clinical features of mineralocorticoid excess or androgen excess

Clinical spectrum broad - many subjects asymptomatic

Question 4

How can mutations/polymorphisms cause reduced sensitivity to glucocorticoids?

Answer 4

Can alter the protein structure of the glucocorticoid receptor