Therapy rationale

Question 1

Where are endogenous corticoids released from?

Answer 1

Adrenal cortex

Question 2

What do mineralocorticoids (aldosterone) affect?

Answer 2

Water and electrolyte balance

Question 3

What do glucocorticoids (HC) affect?

Answer 3

Carbohydrate and protein metabolism.

Anti inflammatory and immunosuppressive effects

Question 4

What diseases have deficiencies in corticoids?

Answer 4

Addisons disease

Question 5

What diseases have excess corticoids?

Answer 5

Cushings syndrome

Conns syndrome

Question 6

Do corticoids inhibit the early, late or both tages of inflammatory response?

Answer 6

Both

Question 7

What do corticoids do?

Answer 7

Decrease extravasation
Inhibit cell activation
Decrease production of inflammatory mediators

Question 8

What is the mechanism of action for glucocorticoids?

Answer 8

1. Enter cells and bind to cytoplasmic receptors.
2. Complex translocates to the nucleus to act as transcription factor.
3. Can bind to response elements and activate gene transcription
4. Can bind and repress gene activation
5. Can interact and inhibit binding of other transcription factors

Question 9

What are the metabolic side effects of glucocorticoids?

Answer 9

Osteoporosis
Diabetogenic plus increased appetite
Mineralocortocoid effects- Na/H20 retention, hypertension, oedema, CV events

Question 10

What are TNF and IL-1?

Answer 10

Proinflammatory cytokines involved in cell proliferation and apoptosis (TNF).

Question 11

What is the primary function of TNF and IL-1?

Answer 11

Beneficial activation of innate immune system

Question 12

Excess release of TNF and IL-1 causes what?

Answer 12

Inflammation, tissue destruction and organ damage

Question 13

What are TNF and IL-1 produced by?

Answer 13

LPS-activates monocytes/macrophages

Question 14

Where is IL-1a found?

Answer 14

Mainly cytosolic or membrane bound

Question 15

Where is IL-1b found?

Answer 15

Circulating

Question 16

Where is IL-1 synthesised?

Answer 16

Microtubules

Question 17

ICE inhibitors are what?

Answer 17

Anti inflammatory agents

Question 18

What are the effects of IL-1?

Answer 18

Increase synthesis of COX2 and iNOS.
Increase expression of VCAM and ICAM.
Increase bone erosion.

Question 19

What increases IL-1 mRNA?

Answer 19

C5a

Question 20

What activates ICE in EC and SM cells?

Answer 20

CD40L

Question 21

Type 1 IL-1 receptors are what?

Answer 21

The main receptor

Question 22

Where are type II IL-1 receptors mainly found?

Answer 22

B ells

Question 23

Which receptor is the main receptor and which is the decoy receptor on IL-1 receptors?

Answer 23

type I- main receptor

type II- decoy receptor

Question 24

What causes haemorrhagic necrosis of solid tumours?

Answer 24

TNF

Question 25

What are the funcitonal effects of TNF due to?

Answer 25

upregulation of other cytokines

Question 26

What increase TNF mRNA?

Answer 26

Bac, viruses, TNF, IL-1 and 2

Question 27

TNF can be cleaved from surface by what?

Answer 27

MMPs

Question 28

How many types of TNF receptors are there?

Answer 28

2

Question 29

What does TNFRa do?

Answer 29

recruits caspases-apoptosis

Question 30

What does TNFRII do?

Answer 30

recruits TRAFs-gene transcription

Question 31

What does TNF do?

Answer 31

Stimulates recruitment of neutrophils and monocytes to site of infection and their activation

Question 32

Which of the following is not a TNF effect:
Decreases expression of adhesion molecules on EC.
Stimulates mononuclear phagocytes to synthesise IL-1

Answer 32

Decreases expression of adhesion molecules on EC.

it increases expression

Question 33

What happens in severe cases when large quantities of TNF are released?

Answer 33

Acts on hypothalamus to induce fever.
Induces hepatocytes to increase release of APP.
Prolonged exposure- muscle wasting, inhibition of cardiac contractility, intravascular thrombosis