Corticosteroids Flashcards
(23 cards)
Describe the Hypothalamic Pituitary Adrenal (HPA) Axis
Circadian Rhythm and stress cause release of CRH from the hpythalamus, which acts the pituitary which releases ACTH, acts on adrenal glands which releases Cortisol. Cortisol acts on tissues and causes negative feedback of CRH and ACTH
What zone is responsible for producing Glucocorticoids such as cortisol?
Zona Fasciculata
What zone is repsonsible for producing Mineralcorticoids such as Aldosteone?
The outermost layer - Zona Glomerulosa
What are glucocorticoids widely used as in medicine?
Anti - Inflammatory drugs
What do mineracorticoids such as aldosterone regulate in the kidney?
Electrolyte balance
Why do glucocorticoids have a low activity in the kidney?
Due to the enzyme 11 - B - hydroxysteroid dehydrogenase
What does hydrocortisone equal?
Cortisol
List some exaples of glucorticoids?
Hydrocortisone
Prednisolone
Betamethasone
Beclomethasone - Asthma
Name two mineralcorticoids?
Aldosterone
Fludrocortisone
What does mineralcorticoids do?
Increase Na reabsorbtion in the distal tubule of the kidney
Increase K, H exretion
What can you prescribe with excess MC secretion?
Spironolactone - K + sparing agent used in CHF
How does the activated Glucocorticoid Receptor identify its targret genes in the nucleus?
GC receptor dimers bind to specific hormone repsonse elements (HRE) on target genes
What conditions are associated with too ltlle and too much glucocorticoids?
Too little - Addisons
Too much - Cushing’s syndrome
what are signs of addisons disease ?
Bronze pigmentation of skin Hypoglycemia Postural hypotension Chnages in distribution of hair GI disturbances Weight loss Weakness
What are signs of Cushings?
Euphoria though not always ... Moon face Buffulo hump hyoertension Increased abdominal fat Thin arms and legs, muscle wasting Easily bruising Poor wound healing Osteoporosis
What type of doses of steroids reduces inflammation?
Supraphysiological doses of steroids reduces inflammation
How do corticosteroids ruduce inflammation in SLE/RA?
Decrease in numbers of activated macrophages, T cells especially T helper (CD4+) cells
Decreased IL -1, IL -2 production
Decreased transcription of COX -2, PLA2, IL -2R via inhbiton of AP -1, NFkB signalling
How do corticosteroids reduce inflammation in SLE/RA?
Increased annexin -1 (lipocortin) levels in leukocytes,
inhibition of phospholipase A2
Reduced prostaglandin levels
What is main side effect of glucocorticoids?
Steroids needed for normal immune function
Suppresson of the HPA axis
High doses of steroids are immunosupressive
What are side effects of corticosteroid therapy?
Stemic effects - Cushings syndorme symptoms
Inhaled - oral candidisis, increased pneumonia risk, increased blood glucose
Why do GCs cause osteoporosis?
important to consider when using, e.g prednisolone
GCs inhibit osteoblasts and activate osteoclasts
What treatment is given for cushings syndrome?
Metyrapone: blocker of 11B Hydroxylase 750mg -4g daily divided doses
Ketoconazole: inhibits cortisol synthesis
What is treatment for Addisons disease?
These patients take physiological doses of hydrocortisone and fludrocortisone
