Immunosuppressants

Question 1

How do Corticosteroids work?

Answer 1

Inhibit IL-1 and IL-6 production by macrophages
And
Inhibit all stages of T-cell activation

Question 2

What side effects are associated with corticosteroids?

Answer 2

Cataracts, thrush, hair loss, muscle weakness, think skin, cushings

Question 3

What is the mechanism of action for Azathioprine?

Answer 3

An anti-metabolite

It decreases DNA and RNA synthesis

Question 4

What adverse effects are associated with Azathioprine?

Answer 4

Bone marrow suppression
Increased risk of malignancy
Increased risk of infection

Question 5

What enzyme metabolises 6 mercaptopurine?

Answer 5

TPMT

Question 6

Name the Calcineurin inhibitors you have studied

Answer 6

Ciclosporin

Tacrolimus

Question 7

What is the mechanism of action for calcineurin inhibitors?

Answer 7

They are active against helper T cells, preventing production of IL-2 via calcineurin inhibitors

Question 8

What is the role of calcineurin regarding T cells?

Answer 8

Calcineurin exerts phosphatase activity of activated T cells then nuclear factor migration starts IL-2 transcription

Question 9

What does ciclosporin bind to?

Answer 9

Cyclophilin protein

Question 10

What side effects are associated with calcineurin inhibitors?

Answer 10

Gum hypertrophy
Renal toxicity
BP and EGFR checks required regularly

Question 11

What is the mechanism of action of Mycophenolate Mofetil?

Answer 11

A pro drug that inhibits monophosphate dehydrogenase which is required for guanosine synthesis
Thus impairing B and T cells proliferation

Question 12

Mycophenolate mofetil inhibits what enzyme?

Answer 12

Inosine monophasphate dehydrogenase

Question 13

Mycophenolate mofetil impairs the production of what cells?

Answer 13

B and T cells

Question 14

What are the most common side effects of Mycophenolate mofetil?

Answer 14

Nausea 
Vomiting
Diarrhoea
Myelosuppression
Mouth ulcers

Question 15

What is the mechanism of action for cyclophosphamide?

Answer 15

Cytotoxic agent
Alkylating
Cross links DNA so it cant replicate
Suppresses B and T cell activity

Question 16

What is the main active metabolite of cyclophosphamide?

Answer 16

4-hydroxycyclophosphamide

Question 17

How is cyclophosphamide excreted?

Answer 17

By the kidney

Question 18

What metabolite of cyclophosphamide is toxic to the bladder epithelium and can lead to haemorrhagic cystitis?

Answer 18

Acrolein

Question 19

What is the antidote for Acrolein?

Answer 19

Mesna

And use aggressive hydration

Question 20

What drug is the gold standard for RA?

Answer 20

Methotrexate

Question 21

What enzyme does Methotrexate inhibit?

Answer 21

Dihydrofolate reductase

Question 22

Methotrexate works best during what phase of the cell cycle?

Answer 22

S phase

Question 23

Which immunosuppressive can be used as an abortifactant?

Answer 23

Methotrexate

Question 24

What is the key carrier of 1 carbon subunits in purine and thymidine synthesis?

Answer 24

Tetrahydrofolate

Question 25

What are the side effects of methotrexate that respond to folic acid supplementation?

Answer 25

Mucositis | Marrow suppression

Question 26

Describe the dosing of methotrexate

Answer 26

Weekly

Question 27

What drugs displace methotrexate when it is protein bound?

Answer 27

NSAIDs

Question 28

What is the effect of Sulfasalazine on T cells?

Answer 28

Inhibition of proliferation Possible T cell apoptosis Inhibition of IL-2

Question 29

What is he effect of sulfasalazine on neutrophils?

Answer 29

Reduced chemotaxis | Reduced degranulation

Question 30

Where do biopharmaceuticals come from?

Answer 30

From living systems: Whole blood Blood components Stem cell therapy

Question 31

What are the effects of blocking TNF-a using biologicals?

Answer 31

Decreased inflammation Decreased angiogenesis Decreased joint destruction

Question 32

What is a major risk of Anti-TNF-a therapy?

Answer 32

TB reactivation This is because TNF-a is released by macrophages in response to M.Tb. TNF-a is essential for development and maintenance of granulomata.

Question 33

What does Rituximab bind to?

Answer 33

CD20 on B cells | Causes B cell apoptosis