Immunosuppression

Question 1

Describe Rheumatoid Arthritis. (3)

Answer 1

An autoimmune inflammatory condition initially localised to the synovium before spreading to the dissolution of bone and cartilage.

Question 2

Describe the causes of RA. (2)

Answer 2

Increased amount of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) compared to anti-inflammatory ones.

Question 3

Describe the symptoms of RA. (5)

Answer 3

Morning stiffness for over an hour
Swelling of over 3 joints
Rheumatic nodules
Serum rheumatoid factor or anti-CCP antibodies
X Ray changes

Question 4

Describe the treatment goals of RA. (2)

Answer 4

Relieve symptoms

Prevent joint destruction

Question 5

Describe the treatment goals for SLE and vasculitis. (3)

Answer 5

Relieve symptoms
Reduce mortality
Prevent organ damage from disease process or therapies

Question 6

Describe the MoA of azathioprine. (2)

Answer 6

Antiproliferative immunosuppressant - interferes with DNA / RNA synthesis.

Question 7

Describe the use of azathioprine. (3)

Answer 7

SLE
Vasculitis
IBD as maintenance therapy

Question 8

Describe the consideration that need to be made when prescribing azathioprine. (3)

Answer 8

It is metabolised by the TPMT gene, which is highly polymorphic, so just test TPMT levels before prescribing.

Question 9

Describe the adverse effects of azathioprine. (4)

Answer 9

Bone marrow suppression - monitor FBC
Increased risk of malignancy esp in transplant
Increased risk of infection
Hepatitis - monitor LFTs

Question 10

Name two calcineurin inhibitors. (2)

Describe their MoA (2)

Answer 10

Ciclosporin
Tacrolimus
Inhibits calcineurin, which normally activates T cells through IL-2

Question 11

Describe the common uses for calcineurin inhibitors. (4)

Answer 11

Widely in transplants, atopic dermatitis, psoriasis.

Less common in rheumatology.

Question 12

Describe the main ADR of calcineurin inhibitors. (2)

Answer 12

Renal toxicity. Need to monitor BP and eGFR regularly.

Question 13

Describe the metabolism of calcineurin inhibitors, and why this is important. (2)

Answer 13

CYP450 metabolised

DDIs common.

Question 14

Describe the MoA for mycophenolate mofetil. (4)

Answer 14

Antiproliferative immunosuppressant that inhibits an enzyme used in guanine synthesis, so impairs B and T cell proliferation, but spares other cells due to their guanine salvage pathways.

Question 15

Describe the common uses for mycophenolate mofetil. Explain why is might not be first choice. (3)

Answer 15

Induction therapy in SLE and vasculits.

Takes 6 weeks to kick in fully.

Question 16

Describe cyclophosphamide. (2)

Answer 16

An alkylating agent that forms cross links in DNA, especially active in T and B cells.

Question 17

Describe indications for cyclophosphamide. (5)

Answer 17

Lymphoma, leukaemia, solid cancers, lupus nephritis, ANCA-vasculitis.

Question 18

Give three important considerations when prescribing phosphamide. (6)

Answer 18

Given as a pro-drug and metabolised by CYP450s - DDIs common.
Excreted renally, but one metabolite toxic to the bladder - can cause haemorrhagic cystitis - give Mensa and aggressively hydrate.
Can cause infertility - related to dose and age.

Question 19

Describe the MoA of methotrexate in its common indications. (8)

Answer 19

Malignancy - inhibits dihydrofolate reductase to impair DNA and RNA synthesis.
RA / Crohns / psoriasis / vasculitis - T cell activation inhibition.

Question 20

Explain the method of administration on methotrexate. (3)

Answer 20

Low oral bioavailability and common N+V when given oral so often given SubCut.

Question 21

Describe the never event relating to methotrexate prescribing. (2)

Answer 21

Daily dosing - should always be given weekly.

Question 22

Describe the commonest DDI relating to methotrexate. (3)

Answer 22

Can’t be taken with NSAIDs - fall in GFR can raise blood levels of methotrexate quickly to toxic levels.

Question 23

Describe the common ADRs of methotrexate. (4)

Answer 23

Mucositis
Marrow suppression - infection risk
Hepatitis and cirrhosis
Highly teratogenic and abortifascient

Question 24

Describe the MoA for corticosteriods in Immunosuppression. (2)

Answer 24

Prevents IL-1 and IL-6 Production by macrophages to inhibit all stages of T cell activation.

Question 25

Describe the Side effects of corticosteriods. (5)

Answer 25

``` Osteoporosis Cataracts Diabetes Glaucoma Buffalo hump Similar to “old age” ```

Question 26

Describe sulphasalazine. (3)

Answer 26

Non-biological, non-immunosuppressant. | Anti-inflammatory and infection fighting portions - T cell inhibition, reduced neutrophil degranulation.

Question 27

Describe indications for sulphasalazine use. (4)

Answer 27

Poorly absorbed so used mostly in IBD. | Safe in pregnancy, few DDIs, doesn’t need monitoring.

Question 28

Describe hydrochloroquine. (4)

Answer 28

Increases pH inside macrophage lysosomes. Non-immunosuppressant. Used primarily for malaria, but also RA, vasculitis, SLE.

Question 29

Name two monoclonal antibodies that block TNF-alpha. (2)

Answer 29

Adalimumab | Infliximab

Question 30

Describe the effects of blocking TMF-alpha and three indications for doing so. (6)

Answer 30

Reduced inflammation, reduced joint destruction and reduced angiogenesis. RA, psoriasis, IBD.

Question 31

Describe Rituximab. (2) | Describe its indications for use. (4)

Answer 31

Monoclonal antibody that causes B cell apoptosis. | Used in RA, SLE, lymphoma and vasculitis.

Question 32

Describe the functions of interleukins 1-5. (5)

Answer 32

``` 1 - hot - fever 2 - T - increases T cell 3 - bone - stimulates bone marrow 4 - E - IgE 5 - A - IgA Hot T Bone stEAk. ```