Therapy rationale Flashcards
Where are endogenous corticoids released from?
Adrenal cortex
What do mineralocorticoids (aldosterone) affect?
Water and electrolyte balance
What do glucocorticoids (HC) affect?
Carbohydrate and protein metabolism.
Anti inflammatory and immunosuppressive effects
What diseases have deficiencies in corticoids?
Addisons disease
What diseases have excess corticoids?
Cushings syndrome
Conns syndrome
Do corticoids inhibit the early, late or both tages of inflammatory response?
Both
What do corticoids do?
Decrease extravasation
Inhibit cell activation
Decrease production of inflammatory mediators
What is the mechanism of action for glucocorticoids?
- Enter cells and bind to cytoplasmic receptors.
- Complex translocates to the nucleus to act as transcription factor.
- Can bind to response elements and activate gene transcription
- Can bind and repress gene activation
- Can interact and inhibit binding of other transcription factors
What are the metabolic side effects of glucocorticoids?
Osteoporosis
Diabetogenic plus increased appetite
Mineralocortocoid effects- Na/H20 retention, hypertension, oedema, CV events
What are TNF and IL-1?
Proinflammatory cytokines involved in cell proliferation and apoptosis (TNF).
What is the primary function of TNF and IL-1?
Beneficial activation of innate immune system
Excess release of TNF and IL-1 causes what?
Inflammation, tissue destruction and organ damage
What are TNF and IL-1 produced by?
LPS-activates monocytes/macrophages
Where is IL-1a found?
Mainly cytosolic or membrane bound
Where is IL-1b found?
Circulating
Where is IL-1 synthesised?
Microtubules
ICE inhibitors are what?
Anti inflammatory agents
What are the effects of IL-1?
Increase synthesis of COX2 and iNOS.
Increase expression of VCAM and ICAM.
Increase bone erosion.
What increases IL-1 mRNA?
C5a
What activates ICE in EC and SM cells?
CD40L
Type 1 IL-1 receptors are what?
The main receptor
Where are type II IL-1 receptors mainly found?
B ells
Which receptor is the main receptor and which is the decoy receptor on IL-1 receptors?
type I- main receptor
type II- decoy receptor
What causes haemorrhagic necrosis of solid tumours?
TNF
What are the funcitonal effects of TNF due to?
upregulation of other cytokines
What increase TNF mRNA?
Bac, viruses, TNF, IL-1 and 2
TNF can be cleaved from surface by what?
MMPs
How many types of TNF receptors are there?
2
What does TNFRa do?
recruits caspases-apoptosis
What does TNFRII do?
recruits TRAFs-gene transcription
What does TNF do?
Stimulates recruitment of neutrophils and monocytes to site of infection and their activation
Which of the following is not a TNF effect:
Decreases expression of adhesion molecules on EC.
Stimulates mononuclear phagocytes to synthesise IL-1
Decreases expression of adhesion molecules on EC.
it increases expression
What happens in severe cases when large quantities of TNF are released?
Acts on hypothalamus to induce fever.
Induces hepatocytes to increase release of APP.
Prolonged exposure- muscle wasting, inhibition of cardiac contractility, intravascular thrombosis
