Corticosteroids

Question 1

Describe the Hypothalamic Pituitary Adrenal (HPA) Axis

Answer 1

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

Question 2

What zone is responsible for producing Glucocorticoids such as cortisol?

Answer 2

Zona Fasciculata

Question 3

What zone is repsonsible for producing Mineralcorticoids such as Aldosteone?

Answer 3

The outermost layer - Zona Glomerulosa

Question 4

What are glucocorticoids widely used as in medicine?

Answer 4

Anti - Inflammatory drugs

Question 5

What do mineracorticoids such as aldosterone regulate in the kidney?

Answer 5

Electrolyte balance

Question 6

Why do glucocorticoids have a low activity in the kidney?

Answer 6

Due to the enzyme 11 - B - hydroxysteroid dehydrogenase

Question 7

What does hydrocortisone equal?

Answer 7

Cortisol

Question 8

List some exaples of glucorticoids?

Answer 8

Hydrocortisone
Prednisolone
Betamethasone
Beclomethasone - Asthma

Question 9

Name two mineralcorticoids?

Answer 9

Aldosterone

Fludrocortisone

Question 10

What does mineralcorticoids do?

Answer 10

Increase Na reabsorbtion in the distal tubule of the kidney

Increase K, H exretion

Question 11

What can you prescribe with excess MC secretion?

Answer 11

Spironolactone - K + sparing agent used in CHF

Question 12

How does the activated Glucocorticoid Receptor identify its targret genes in the nucleus?

Answer 12

GC receptor dimers bind to specific hormone repsonse elements (HRE) on target genes

Question 13

What conditions are associated with too ltlle and too much glucocorticoids?

Answer 13

Too little - Addisons

Too much - Cushing’s syndrome

Question 14

what are signs of addisons disease ?

Answer 14

Bronze pigmentation of skin 
Hypoglycemia 
Postural hypotension
Chnages in distribution of hair 
GI disturbances 
Weight loss 
Weakness

Question 15

What are signs of Cushings?

Answer 15

Euphoria though not always ...
Moon face 
Buffulo hump 
hyoertension
Increased abdominal fat 
Thin arms and legs, muscle wasting 
Easily bruising 
Poor wound healing 
Osteoporosis

Question 16

What type of doses of steroids reduces inflammation?

Answer 16

Supraphysiological doses of steroids reduces inflammation

Question 17

How do corticosteroids ruduce inflammation in SLE/RA?

Answer 17

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

Question 18

How do corticosteroids reduce inflammation in SLE/RA?

Answer 18

Increased annexin -1 (lipocortin) levels in leukocytes,
inhibition of phospholipase A2
Reduced prostaglandin levels

Question 19

What is main side effect of glucocorticoids?

Answer 19

Steroids needed for normal immune function
Suppresson of the HPA axis
High doses of steroids are immunosupressive

Question 20

What are side effects of corticosteroid therapy?

Answer 20

Stemic effects - Cushings syndorme symptoms

Inhaled - oral candidisis, increased pneumonia risk, increased blood glucose

Question 21

Why do GCs cause osteoporosis?

important to consider when using, e.g prednisolone

Answer 21

GCs inhibit osteoblasts and activate osteoclasts

Question 22

What treatment is given for cushings syndrome?

Answer 22

Metyrapone: blocker of 11B Hydroxylase 750mg -4g daily divided doses
Ketoconazole: inhibits cortisol synthesis

Question 23

What is treatment for Addisons disease?

Answer 23

These patients take physiological doses of hydrocortisone and fludrocortisone