Therapeutic Use of Adrenal Steroids Flashcards
Name the three parts of the adrenal cortex and the steroids that each produces.
Zona Glomerulosa – Aldosterone
Zona Fasciculata – Cortisol
Zona Reticularis – Sex Steroids
What hormone controls the production of adrenal sex steroids?
ACTH
What controls the production of aldosterone?
Angiotensin II
State four triggers of aldosterone release
Hyperkalaemia
Hyponatraemia
Drop in renal blood flow
Beta-1 stimulation
What is the principle action of aldosterone?
Increases Na+ reabsorption
Increases K+ excretion
State three differences between glucocorticoid receptors and mineralocorticoid receptors.
GRs are widely distributed; MRs have a discrete distribution
GRs are selective for glucocorticoids; MRs cannot distinguish between cortisol and aldosterone
GRs have a low affinity for cortisol; MRs have a high affinity for cortisol
Describe how MRs are protected from cortisol stimulation.
There is an enzyme called 11-beta hydroxysteroid dehydrogenase-2, which converts cortisol to the inactive cortisone to prevent it from interacting with mineralocorticoid receptors. NOTE: 11-beta-HSD-1 converts cortisone back to cortisol
Why do you get hypokalaemia in Cushing’s syndrome?
In Cushing’s syndrome there is so much cortisol that it overloads the 11-beta-HSD-2 system so the cortisol binds to the mineralocorticoid receptors and has mineralocorticoid effects.
Name three glucocorticoid drugs in order of decreasing mineralocorticoid activity.
Hydrocortisone (highest mineralocorticoid activity)
Prednisolone
Dexamethasone
What does prednisolone tend to be used for?
Immunosuppression
What does dexamethasone tend to be used for?
Acute anti-oedema
E.g. used clinically for things like brain metastases where there is a lot of oedema
Name an aldosterone analogue.
Fludrocortisone
How are all these drugs administered?
Orally
Describe the extent of plasma protein binding in each of these four drugs.
They bind to plasma proteins – corticosteroid binding globulin + albumin
Hydrocortisone is extremely plasma protein bound –90-95% Prednisolone is less bound
Dexamethasone and fludrocortisone are even less bound
Fludrocortisone only binds to albumin
Where are the corticosteroid drugs metabolised and how are they excreted?
Hepatic metabolism
Excreted in the bile and urine