Corticosteroids Flashcards
What is the precursor molecule of steroid hormones?
Cholesterol
Corticosteroids can be classified into:
Gluco/mineralcorticoids
Cortisol is what type of corticosteroid?
Glucocorticoids
Aldosterone is what type of corticosteroid?
Mineralcorticoids
Catabolism define
Breakdown of complex molecules in living organisms to form simpler ones
Location of corticosteroids
Adrenal glands
How is glucocorticoid release regulated?
Under the control of the hypothalamic- pituitary -adrenal (HPA axis)
Subject to negative feedback control
Glucocorticoid has a negative feedback effect. Meaning?
It reduces further release of itself via a negative feedback effect at the level of anterior pituitary and hypothalamus
Glucocorticoid release : mechanism
- Hypothalamus release CRH
- CRH has a +ve effect on the anterior pituitary: induces release of ACTH
- ACTH stimulates the adrenal gland
ACTH
Adrenocorticotrophic hormone
Cushing’s syndrome : state
Exposure to excessive levels of endogenous glucocorticoids
Eg. Possibly excessactivity in tumour in the pituitary or excess ACTH causing excess cortisol release
Describe Cushing’s syndrome: effects
Moon face, with red cheeks
Easy bruising
Buffalo hump
Euphoria
Increased abdominal fat
Poor wound healing
GRE
Glucocorticoid response element
Corticosteroids act on what receptors? Located where?
Nuclear receptors
Located in the cytoplasm, where they can migrate to the nucleus and causes changes in gene transcription
TM
Transcriptional machinery
Molecular mechanism of action ofglucocorticoids upregulating TM
- section of the DNA associated with a GRE-binds to activated glucocorticoid receptor to bring about its effect
- TM goes along DNA operating at low levels
- glucocorticoid receptor moves into the nudeus, the nuclear receptors dimerise and bind to the gre—> activate/promote activity within gene TM
Molecular mechanism of action ofglucocorticoids in repressing the activity of TF ( transcription factors) on the TM to reduce transcriptional activity
Some GRE are referred to as negative GRE (nGRE)
- TF in absence of glucocorticoid has stimulatory effect on TM
- when glucocorticoid receptor dimerises, moves into nucleus and binds to recognition site
- gets rid of TF, which then loses its stimultary effect on TM= reduced transcriptional activity
Examples of therapeutically used glucocorticoids
- All readily absorbed from the get
Hydrocortisone, synthetic glucocorticoids, dexamethason
Hydrocortisone binds to? Metabolism?
Corticosteroid- binding globulin (transcortin) and to albumin in the blood and is extensively metabolised in the gut wall and liver
Synthetic glucocorticoids bind to? Metabolism?
Bind to albumin but not to transcortin and are more slowly metabolised in the liver, giving them a longer duration of action
Dexamethason
Glucocorticoid
Most potent and has the vast mineralcorticoid activity
Topical administration of glucocorticoids can?
Deliver high concentration at a target site : w/o adversely/excessively increasing systemic circulatory levels of glucocorticoid—> reduced side effects associated with excess of glucocorticoid hormone
Side effect of glucocorticoid therapy
Suppression of response to infection or injury
Cushing’s syndrome
Hyperglycaemia
CNS effects: euphoria and psychosis (short term administration) , depression w/ chronic treatment
Sudden withdrawl of drugs after prolonged therapy may result in?
Acute adrenal insufficiency b/c of suppression of capacity to synthesis corticosteroids
—> takes time for body to return to situation where it responds normally to normal circulatory levels of cortisol
