Steroids Flashcards
2 Types of steroid?
Hormonal (corticosteroids and sex hormones) Non hormonal (cholesterol)
Name the 4 zones of the adrenal gland (outer->inner)
Zona glomerulosa
Zona fasciculata
Zona reticularis
Adrenal medulla
Where are mineralocorticoids produced? eg?
In the zona glomerulosa of the adrenal gland
e.g. aldosterone
Where are glucocorticoids produced? eg?
In the zona fasciclata of the adrenal gland
e.g. cortisol
Where are androgens produced? eg?
in the zona reticularis of the adrenal gland
e.g. testosterone
What is produced int he adrenal medulla? eg?
Catecholamines (e.g. adrenaline)
What is formed in the zona reticularis of the adrenal gland?
Androgens (testosterone)
What is formed in the zona fasciculata?
Glucocorticoids (cortisol)
What is formed in the zona glomerulosa?
Mineralocorticoids (aldosterone)
What is cholesterol’s main function?
Regulates fluidity and function of phospholipid bilayer membranes
Makes membrane less deformable and less water permeable (so no cell wall needed)
What controls the rate of cholesterol production?
HMG CoA reductase (inhibited by statins)
What is the main glucocorticosteroid in humans?
Cortisol
What do glucocorticosteroids do?
Prepare for starvation (catabolic) -hyperglycaemia -mobilisation of lipids -breakdown of proteins and anti inflammatory
Name two inhaled GCS drugs?
Fluticasone (for asthma)
Beclomethasone
Name two topical GCSs
Hydrocortisone
Betamethasone (for eczema)
Name two systemic GCS drugs
Prednisolone
Dexamethasone
What are Prednisolone and Dexamethasone used for?
To treat systemic arthritis, inflammatory bowel disease, cerebral oedema, some types of leuekmia
What is Beclomethasone?
Inhaled GCS to treat asthma
How do GCS drugs work?
Bind to cytoplasmic GRs (glucocorticoid receptors) and modulate transcription of hundreds of inflammatory genes
(block transcription of pro-inflam and induce transcription of anti-inflam)
Activates Annexin-1 (phospholipidase-A2 inhibitor) so arachadonic acid can’t be formed-> no prostagladins of leukotrienes
Give 3 examples of anti-inflammatory proteins
IL-10, Anexin-1 and Ribonucleases (break down inflam mRNAs)
Give 5 examples of pro-inflammatory proteins
COX-2, cytokines, immunoglobulins (IgG, IgE), complements and adhesion molecules
What is Cushing’s disease?
Give 9 effects on body
Syndrome caused by either overproduction of cortisol or overuse of synthetic GCS drugs
Cateracts, moon face, red cheeks, benign intercranial hypertension, euphoria, buffalo hump, thinning of skin (bruises and poor wound healing), osteoporosis and muscle wasting of arms and legs
How can overproduction of cortisol be treated?
By Metyrapone
How else to GCS affect the body?
Reduces proliferation, adhesion, migration, activation and survival of inflammatory leukocytes
Reduces oedema and impairs fibrosis and wound healing
Why can’t GCS drugs be stopped suddenly?
-ve feedback occurs, causing atrophy of adrenal gland in the long term (anterior pituitary stops producing ACTH)
ACTH= adrenocroticotrophic hormone
What is the series of events that causes production of cortisol?
Stress, shock, starvation, pain ->
Hypothalamus releases corticotrophin releasing factor ->
Anterior pituitary releases ACTH ->
Adrenal gland releases cortisol
What is the main endogenous mineralocorticoid? And what triggers its release?
Aldosterone
Released from zona glomerulosa when low plasma Na+ and indirectly by renin-angiotensin sytem
What are the actions of aldosterone?
Acts of MR (mineralocorticoid receptors) in cytoplasm of kidney tubule epithelial cells
Increases transcription of epithelial Na+ channels–> increased Na+ and water reabsorption into blood -> slat and water are conserved while K+ and H+ are excreted
What is Fludrocortisone?
Mineralocorticoid receptor agonist
Used as replacement therapy in adrenal insufficiency (Addison’s disease)
What drug is used to treat Addison’s Disease
Adrenal insufficiency so the MR agonist Fludrocortisone
Name a diuretic that is also used in hyperaldosternism
Spironolactone, competitive MR antagonist
Reduces blood volume in hypertension while preventing hypokaleamia
What is Fludrocortisone?
An MR agonist used to treat Addison’s disease
Increases volume of blood and may cause hypokalaemia
What is Spironolactone?
MR antagonist -> diuretic that prevents hypokaleamia