Corticosteroids Flashcards
Corticosteroids derive from which organic molecule?
Cholesterol
What can steroid hormones form
Sex hormones
Corticosteroid hormones
What are the two types of corticosteroid hormones?
Glucocorticoids and mineralcorticoids
What do glucocorticoids do and give an example
They have a role in regulation of glucose metabolism and synthesis.
Cortisol:
Decrease carbohydrate uptake and ultilisation
Increased protein metabolism
Regulatory effects on host defence mechanisms
What do mineralcorticoids do and give an example
They link to water and salt balances
Aldosterone:
Regulate water and electrolyte balance
Where are BOTH glucocorticoids and mineralocorticoids produced?
Adrenal glands
Where are mineralocorticoids synthesised?
Zona glomerulosa (outermost layer on adrenal cortex)
Where are glucocorticoids synthesised?
Zona fasciculata (middle layer on adrenal cortex)
How are corticosteroids regulated?
They are under the control of the hypothalamic-pituitary- adrenal (HPA) axis
What is Cushing’s syndrome and what are the symptoms for it?
When there is overactivity and exposure to excessive levels of endogenous glucocorticoids
The symptoms are: Hypertension Easy bruising Increased abdominal fat Thinning of skin and thin arms and legs Osteoporosis Avascular necrosis of femur
What is Addison’s disease?
When there is adrenal insufficiency
How does dimerisation of the receptors lead to the inhibition of transcription?
After the dimerisation of the receptors, they bind to the recognition site on DNA
The dimerisation of the receptors binds to the nGRE, repressing the activity of transcription factors which inhibits transcription
Glucocorticoids can also silence proinflammatory genes. What is this called?
Gene transrepression
How do glucocorticoids silence proinflammatory genes?
The receptors bind to the TFs Fos and Jun which inhibit transcription of AP-1.
This means there is less response to cytokines, growth factors, stress and bacterial and viral infections
Which specific pathway silences proinflammatory genes?
The NKkB pathway
Where are glucocorticoids absorbed and metabolised?
They are readily absorbed in the gut
They are extensively metabolised in the gut wall and liver
How do hydrocortisones bind in the blood?
Hydrocortisone binds to:
- corticosteroid binding globulin (transcortin)
- albumin in the blood
What are the pharmacokinetics of synthetic glucocorticoids?
Only bind to albumin and are more slowly metabolised in the liver
How are glucocorticoids usually administered?
Usually tropical to deliver high concentration
What are the side effects of glucocorticoid therapy?
Suppression of the response to infection or injury
Cushing’s syndrome
Osteoporosis
Hyperglycaemia
Muscle wasting
CNS effects such euphoria and psychosis, depression
