Steroids

Question 1

What are corticosteroids used for

Answer 1

• these are widely used int he treatment of inflammatory and autoimmune diseases

Question 2

what is cortisol known as

Answer 2

stress hormone

Question 3

name the three phases of stress and describe them

Answer 3

• Alarm 6-48 hours
• Resistance – chronic stress 2 days to 1 months
• Exhaustion (pathogenic stress) longer than 3 months

Question 4

what happens to cortisol when you are stress

Answer 4

• normally the cortisol levels undergo a circadian rhythm and are high in the morning and slowly decrease throughout the day
• when you are stressed the cortisol levels can rise and stay risen throughout the day
• they can be higher than the normal circadian rhythm

Question 5

describe how cortisol can be goo and bad for you

Answer 5

• as you increase cortisol it can increase your activity until it gets too high then it can decrease your activity

Question 6

What do corticosteroids do

Answer 6

• these stop the rebound response to infection or traumatic episode

Question 7

what are the sides effects of corticosteroids

Answer 7

Main ones

• glycosuria
• hypertension
• glaucoma
• osteoporosis
• juvenile growth retardation

others

• Oedema
• Weight gian
• Myopathy
• Hyperlipidamiea
• Thrombosis
• Gi bleeding
• Peptic ulcers
• Pancretitis
• Colonic performation
• Cataracts
• Insomnia
• Depression/psychosis
• Increased infection risk

Question 8

what is the action of corticosteroids on osteoblasts and osteoclasts

Answer 8

– can cause osteoblast to decrease and cause osteoclast to decrease but the amount of decrease is less than osteoblast therefore the net effect is the breakdown of bone
- can eventually cause avascular necrosis

Question 9

what do osteoclasts do basically

Answer 9

break down bone

Question 10

what do osteoblasts do basically

Answer 10

build up bone

Question 11

what is avascular necrosis

Answer 11

– this is due to the loss of blood vessels going to that area of the bone

Question 12

what is the biggest cause of hip replacement in the UK

Answer 12

avascuarl necrisosi

Question 13

what is caused by excess corticosteroids/cortsiol

Answer 13

• Caused by excess of corticosteroids in the body

- Caused by excess of cortisol

Question 14

what is caused by decreased levels of corticosteroids and cortisol

Answer 14

• Caused by decreased corticosteroids in the body

- Reduction of cortisol

Question 15

Name some functions of corticosteroids

Answer 15

cardiovascular
- hypertnesvie

carbohydrate metabolism
- hyperglycaemia due to inhibition of insulin and stimulation of glucagon

lipid metabolism
- increased lipolysis in adipocytes

CNS
- regulation of neuronal excitability

imune suste
- immunosupresvie

kidney
- permissive action of tubular function and glomuerlar filtration

skeletal system
- maitnaince of msucuarl tone

Question 16

How do the corticosteroids work

Answer 16

• The glucocorticoids receptor is part of a wider steroid family and you can pin point two different forms of the glucocortoicoid receptor the alpha and beta form
• The alpha form binds steroid and the beta fomrs does not bind steroid but it still binds DNA and block and change the genomic transcription and translation of a wide variety of gene
• The beta one is a dominaint negative repressor

Question 17

what are glucocorticoid receptors split into

Answer 17

genomic slow

non genomic rapid

Question 18

what does genomic slow do

Answer 18

transactivation of gene transcription by direct interaction with DNA or
transrepression by interaction with other proteins in cytoplasm or nucleus

Question 19

what does non genomic rapid do

Answer 19

Interaction of GC with cytoplasmic GR
Interaction of GC with plasma membrane GR
Interaction of GC with membranes

Question 20

why can glucocorticoids easily enter cells

Answer 20

because it is lipophillic

Question 21

how does corticosteroids have trans-repressive action

Answer 21

• usually The TNF binds to its receptor
• This receptor activates transcription factors
• When these are activated this complex moves to the nucleus where it can have pro-inflammaotry properties by binding to the receptors of the geens
• But if the corticoisteroid binds to the glucocorticoid receptor this can activate heat shock proteins and cause receptors to dimerise
• this can cause cross couples with transcription factors and inhibits them from transcribing genes

Question 22

what are the possible non genomic mechanisms of glucocorticoid action

Answer 22

• 1, membrane GR
• 2, Cytosolic GR signalling
• 3, Intercollation in membranes

Question 23

Describe the non genomic mechanisms of glucocorticoid action

Answer 23

Membrane GR- tells the inside of the cell that they need to prepare for the steroid

Cytosolic GR singllaing
- If there is a lot of steroid this can signal immediately to the cell such as PKC which are more rapid then the genomic effects – certain cell types like signalling in this way to get an immediate response

Intercollation in membrane
- Membrane recpetors cant interact so the cell function drops of and the steroid stops these processes

Question 24

What are the synthetic forms of glucortocoid

Answer 24

 Dexamethasone.
 Betamethasone.
 Prednisone.
 Prednisolone.

Question 25

When do non genomic effects happen

Answer 25

 Non-genomic effects occur when activated GR binds to proteins in the cytoplasm or membranes to cause an effect.

Question 26

What is transactivation

Answer 26

 Activated receptors translocate into the nucleus.  They bind to glucocorticoid receptor elements in the promotor region of the DNA to regulate gene expression.  This is called transactivation.

Question 27

What is the difference between transactivation and trans repression

Answer 27

 Activated receptors translocate into the nucleus.  They bind to glucocorticoid receptor elements in the promotor region of the DNA to regulate gene expression.  This is called transactivation.  But, the GR can also bind to the DNA where transcription factors would, causing prevention of gene transcription.  This called genomic transrepression.