Corticosteroids Flashcards
What are corticosteroids?
They are hormones derived from cholesterol and produced in the ADRENAL CORTEX.
What are the main corticosteroids?
- Cortisol
- Aldosterone
What 2 categories of corticosteroids does cortisol and aldosterone split into?
Cortisol = Glucocorticoids Aldosterone = Mineralcorticoids
What is the purpose of corticosteroids?
Lowers inflammation in the body and thus, reduces the immune system activity in the body.
How does cortisol act?
Acts via the glucocorticoid receptors.
How does aldosterone act?
Acts via the mineralocorticoids receptors.
What does cortisol do?
Acts on carbohydrate and protein metabolism.
Regulates host defence mechanisms.
What does aldosterone do?
Regulates water and electrolyte balance.
ESSENTIAL = sodium conservation in the kidney and sweat glands.
Where are glucocorticoids made?
Zona Fasiciculata
Where are mineralocorticoids made?
Zona Glomerulosa
How is glucocorticoid release regulated?
It is regulated by the HPA axis and engages with NEGATIVE feedback control.
What is a competitive inhibitor involved with glucocorticoid release?
Metyrapone
What is the purpose of metyrapone?
Reduces glucocorticoids when there is an OVERLOAD.
This inhibits beta - hydroxylase which INHIBITS cortisol.
What is Cushing’s syndrome?
This is a syndrome which occurs due to excessive levels of endogenous glucocorticoids.
What is Addison’s syndrome?
This is a syndrome which occurs due to very little levels of corticosteroids in the body.
What is the difference between Cushing’s syndrome and Addison’s syndrome?
Cushing’s produces TOO MUCH hormone whereas Addison’s produces TOO LITTLE hormone.
What are some symptoms of Cushing’s syndrome?
Increased abdominal fat
Easy bruising
Hypertension
Thinning of the skin
What are the 2 pathways glucocorticoids can take in terms of mechanism of action?
Upregulate transcriptional machinery OR repress the activity of transcription factors.
What is the molecular mechanism of action of glucocorticoids?
Dimerized glucocorticoids go bind to recognition sites on DNA.
What happens regarding up regulating transcriptional machinery?
Glucocorticoids BIND to the glucocorticoid receptor = Ligand binding results in a nuclear receptor being activated.
What happens regarding repressing the activity of transcription factors?
Influences multiple signal transduction.
Switching off multiple activated inflammatory genes via inhibition of HAT and HDAC2.
What is gene transrepression?
One protein represses the activity of a second protein.
This results in silencing pro inflammatory genes.
What is the action which occurs on inflammatory cells?
There is a decreased number of neutrophils leaving the blood vessels and reduced activation of neutrophils // macrophages // mast cells.
There is a decreased activation of T - Helper cells.
There is a decreased fibroblast function.
What are some examples of synthetic therapeutically used glucocorticoids?
Cortisone
Prednisone
Betamethasone
Dexamethasone
What are some examples of natural therapeutically used glucocorticoids?
Cortisol
Which glucocorticoid is the most potent and thus has the least mineralocorticoid activity?
Dexamethasone
What is the mechanism of synthetic glucocorticoids?
They bind to albumin but NOT to transcortin. They are MORE SLOWLY synthesised thus giving them a LONGER DURATION of action.
What is the mechanism of cortisol glucocorticoids?
Binds to a corticosteroid - binding albumin and thus, is extensively metabolised in the gut wall.
What diseases are synthetic glucocorticoids used to treat?
Myeloma Renal disorders Bronchial Asthma Bell's Palsy Organ transplantation
What type of administration is used to deliver glucocorticoids?
Topical Administration
What are the side effects of glucocorticoid therapy?
Cushing's syndrome Hyperglycaemia Osteoporosis Muscle Wasting Cataracts // Glaucoma Easy bruising
