Steroids Flashcards
What are corticosteroids used for
- these are widely used int he treatment of inflammatory and autoimmune diseases
what is cortisol known as
stress hormone
name the three phases of stress and describe them
- Alarm 6-48 hours
- Resistance – chronic stress 2 days to 1 months
- Exhaustion (pathogenic stress) longer than 3 months
what happens to cortisol when you are stress
- 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
describe how cortisol can be goo and bad for you
- as you increase cortisol it can increase your activity until it gets too high then it can decrease your activity
What do corticosteroids do
- these stop the rebound response to infection or traumatic episode
what are the sides effects of corticosteroids
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
what is the action of corticosteroids on osteoblasts and osteoclasts
– 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
what do osteoclasts do basically
break down bone
what do osteoblasts do basically
build up bone
what is avascular necrosis
– this is due to the loss of blood vessels going to that area of the bone
what is the biggest cause of hip replacement in the UK
avascuarl necrisosi
what is caused by excess corticosteroids/cortsiol
- Caused by excess of corticosteroids in the body
- Caused by excess of cortisol
what is caused by decreased levels of corticosteroids and cortisol
- Caused by decreased corticosteroids in the body
- Reduction of cortisol
Name some functions of corticosteroids
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
How do the corticosteroids work
- 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
what are glucocorticoid receptors split into
genomic slow
non genomic rapid
what does genomic slow do
transactivation of gene transcription by direct interaction with DNA or
transrepression by interaction with other proteins in cytoplasm or nucleus
what does non genomic rapid do
Interaction of GC with cytoplasmic GR
Interaction of GC with plasma membrane GR
Interaction of GC with membranes
why can glucocorticoids easily enter cells
because it is lipophillic
how does corticosteroids have trans-repressive action
- 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
what are the possible non genomic mechanisms of glucocorticoid action
- 1, membrane GR
- 2, Cytosolic GR signalling
- 3, Intercollation in membranes
Describe the non genomic mechanisms of glucocorticoid action
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
What are the synthetic forms of glucortocoid
Dexamethasone.
Betamethasone.
Prednisone.
Prednisolone.
When do non genomic effects happen
Non-genomic effects occur when activated GR binds to proteins in the cytoplasm or
membranes to cause an effect.
What is transactivation
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.
What is the difference between transactivation and trans repression
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.
