6.1: Immunosuppression Flashcards Preview

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Flashcards in 6.1: Immunosuppression Deck (27):
1

What is the difference between arthralgia and arthritis?

Both pain and inflammation of a joint, arthralgia is w/o swelling but arthritis is with swelling

2

What is the mechanism of action of corticosteroids?

Lipophilic so binds to intracellular receptor and in the nucleus
Prevents the production of pro-inflammatory interleukins IL-1 and IL-6 by macrophages
Also inhibit all stages of T cell activation (systemic, hence side effects)

3

How does azathioprine work?

Active ingredient is 6-MP, which is broken down into an anti metabolite that decreases purine synthesis, so less DNA and RNA are produced fro WBCs hence the immunosuppression

4

What are some adverse effects of azathioprine?

- bone marrow suppression (hence monitor FBC)
- increased risk of malignancy
- increased risk of infection

- hepatitis (so many LFTs)

5

Ciclosporin and tacrolimus are examples of which type of drug?

Calcineurin inhibitors

6

How do calcineurin inhibitors work?

Prevent IL-2 production in T cells

7

What are some side effects of calcineurin inhibitors?

Many side effects, so rarely used (often used topically for psoriasis)

Nephrotoxic
Headaches
Hepatotoxicity
HTN
Diabetes
Electrolyte disturbances
Hitruism

8

Which DMARD is affected by polymorphism?

Azathioprine

9

How does genetic polymorphism for TPMT affect azathioprine treatment?

TPMT breaks down 6MP, the active ingredient in azathioprine
High levels of TPMT expression will lead to undertreatment (more 6MP broken down)
Low levels of TPMT will lead to increased toxicity

10

How does cyclophosphamide work?

It is a prodrug activated by CYP450s to produce alkykating metabolites (to cross link DNA so it can’t replicate)
Selectively acts on cells with higher mitotic rate

11

What are the man uses of cyclophosphamide?

In cancer chemotherapy (lymphoma, leukaemia, solid cancers)

12

What are some ADRs of cyclophosphamide?

Infertility
Teratogenic
Bladder Ca (toxic metabolite to bladder epithelium)

13

What type of immunosuppressants are the agent of choice is transplant immunosuppression?

Mycophelonate mofetil

14

How do myclophenolate mofetil exert its action?

Inhibits guanosine synthesis
Selective for suppression of B and T lymphocyte proliferation

15

What are some side effects of mycophenolate mofetil?

Nausea
Vomiting
Diarrhoea
Leuko and neutropenia
Myelosuppression
Increased risk of infection

16

What is the gold standard drug for RA?

Methotrexate

17

When should methotrexate be taken?

WEEKLY

(Due to long half lives of metabolites)

18

What is the mechanism of action of methotrexate?

Competitive inhibitor with folate for DHFR
So reduces conversion of BHFR to tetrahydrofolate
Inhibits synthesis of DNA, RNA, and proteins

19

During what phase of the cell cycle does methotrexate act?

S phase

20

What are some side effects of methotrexate?

Cytotoxic during S phase of cell cycle so affects rapidly dividing cells
Mucositis
Myleosuppression
Highly teratogenic!!
Hepatitis
Cirrhosis
Increased infection risk

21

Which DMARD is best for IBD and why?

Sulfasalazine
As it is broken down to its active ingredient in the colon

22

Which DMARD is safe in pregnancy?

Sulfasalazine

23

What is sulfasalazine use in?

IBD and RA

24

What is the active component of sulfasalazine that treats IBD?

5-ASA

25

How does sulfasalazine work in treating RA?

Inhibits T cell proliferation and IL-2 production
T cell apoptosis
Reduces chemotaxis of neutrophils and degranulation

26

What are some side effects of sulfasalazine?

Nausea
Fatigue
Headache
Myelosuppression
Hepatitis

27

What type of drugs in infliximab and how does it work?

Biological agent
Monoclonal antibody that is a TNF-alpha inhibitor
Reduces inflammation, joint destruction and angiogenesis