Corticosteroids Flashcards
What are corticosteroids?
Hormones derived from cholesterol, produced in the adrenal gland
What are the main corticosteroids?
- Cortisol
- Aldosterone
2 categories of corticosteroids that cortisol and aldosterone split into?
Glucocorticoid = Cortisol Mineralocorticoid = Aldosterone
Where does cortisol act?
Acts via glucocorticoid receptors
Where does Aldosterone act?
Acts via mineralocorticoid receptors
What is the role of cortisol?
Acts upon carbohydrates and protein metabolism
Has regulatory effects on host defence mechanisms
What is the role of aldosterone?
Regulates water and electrolyte balance
Sodium conservation in sweat and renal glands.
How is glucocorticoid release regulated?
Regulated by the Hypothalamic - Pituitary - Adrenal (HPA) axis.
-Negative feedback control
Explain the Hypothalamic - pituitary - adrenal axis (HPA) regulation
The hypothalamus releases Corticotropin releasing hormone (CRH), +ve stimulatory effect on:
Anterior Pituitary which releases adrenocorticotropic hormone (ACTH), which causes stimulatory effects on the release of glucocorticoids from the adrenal gland.
What is Cushing’s syndrome?
A result of excessive levels of endogenous glucocorticoids.
What is Addison’s syndrome?
(Adrenal insufficiency)
A result of little levels of corticosteroids in the body.
What is Metyrapone?
A competitive inhibitor involved with glucocorticoid release.
What is the role of Metyrapone?
Reduces glucocorticoids when there’s overload.
This inhibits beta - hydroxylase which inhibits cortisol.
Symptoms of Cushing’s syndrome:
Easy bruising
Thinning of skin
Hypertension
What are the two molecular mechanisms of action for glucocorticoids
Upregulate transcriptional machinery (TM)
Repress the activity of transcriptional factors
The molecular mechanism of action of glucocorticoids:
Dimerized glucocorticoids bind to recognition sites on DNA.
Up regulation of transcriptional machinery?
Glucocorticoids bind to glucocorticoid receptor = Ligand binding results in a nuclear receptor being activated.
What is gene transpression?
One protein represses the activity of second protein.
Results in silencing pro-inflammatory genes.
What happens as a result to repressing the activity of transcription factors?
This influences multiple signal transductions.
Switching off multiple activated inflammatory genes via the inhibition of HDAC2 and HAT.
What action occurs on inflammatory cells?
Decreased no. of neutrophils from blood vessels and reduced activation of neutrophils / macrophages / mast cells.
Theres decreased activation of T-helper cells
Decreased fibroblast function
Examples of natural glucocorticoids therapeutically?
Cortisol
Which glucocorticoid is the most potent and has the least mineralocorticoid activity?
Dexamethasone
The mechanism of synthetic glucocorticoids?
They bind to albumin, not to transcortin.
They are more slowly metabolised in the liver giving them a longer duration of action.
Mechanism of Hydrocortisone?
Binds to corticosteroid-binding globulin and to albumin in the blood, and is extensively metabolised in the gut wall liver.
Examples of therapeutically used synthetic glucocorticoids.
Cortisone
Prednisone
Betamethasone
Dexamethasone
Mechanism of cortisol glucocorticoids?
Binds to corticosteroid-binding albumin and this is extensively metabolised in the gut wall
Diseases that benefit from glucocorticoids therapy?
Myeloma
Bronchial Asthma
Organ transplantation
Administration of glucocorticoids?
Topical Administration
Benefits of Topical administration of glucocorticoids?
They can deliver high concentrations to the target site.
They achieve the desired concentration without adversely/ excessively increasing systemic side effects.
What are the side effects of glucocorticoid therapy?
Cushing’s syndrome
Osteoporisis
Muscle wasting
Euphoria
The difference between Cushing’s syndrome and Addison’s syndrome?
Cushing's = Too much hormones Addison's = Too little hormones
