34 - Steroids Flashcards
What are corticosteroids used for
Treatment of inflammatory/autoimmune diseases
Difference between cortisol and prednisone
Cortisol - Natural
Prednisone - Synthetic
Prednisone is 6x more effective
When is cortisol highest and lowest
Highest on waking and lowest 7:30pm
(diurnal rhythm)
Increases when stressed
Hans Selye’s General Adaptation Syndrome
Alarm, resistance, exhaustion phases of stress
What do corticosteroids do
Prevent the immune system from providing an overzealous response
- The more you increase cortisol, it becomes supressive
What do glucocorticoids maintain
- Inhibit insulin, stimulate glucagon
- Neurochemicals
- Immune reaction, immunosuppressive
- Inflammation
- ADH - Fluid loss
- HT
Side effects of long term glucocorticosteroids
Glycosuria Glaucoma HT Osteoporosis Juvenile growth retardation Avascular necrosis
Why can steroids cause osteoporosis
Steroids reduce osteoblast activity and proliferation
reduce osteoclast activity
Cushing’s syndrome
Excess cortisol
- Upper body obesity, thin arms and legs, thin arms and legs, round face, acne, high BP, fatigue
Where is the human glucocorticoid receptor
Found in the cytoplasm and nucleus in every cell in the body (even cells without nuclei)
Why can GC enter cells easily
As they are lipophilic
2 main forms of HGR and the differences
Alpha - Binds steroids (777aa)
Beta - Doesn’t bind steroids (742aa)
Advantage of 2 different HGRs?
Allows for sensitivity to alpha to change
- in RA there is a higher proportion of beta
Genomic activity of HGR
Slow
- Transactivation
- Transrepressin
Transactivation
Direct interaction with receptor on DNA