Immunosuppression Flashcards

1
Q

Describe Rheumatoid Arthritis. (3)

A

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

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2
Q

Describe the causes of RA. (2)

A

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

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3
Q

Describe the symptoms of RA. (5)

A
Morning stiffness for over an hour
Swelling of over 3 joints
Rheumatic nodules
Serum rheumatoid factor or anti-CCP antibodies
X Ray changes
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4
Q

Describe the treatment goals of RA. (2)

A

Relieve symptoms

Prevent joint destruction

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5
Q

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

A

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

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6
Q

Describe the MoA of azathioprine. (2)

A

Antiproliferative immunosuppressant - interferes with DNA / RNA synthesis.

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7
Q

Describe the use of azathioprine. (3)

A

SLE
Vasculitis
IBD as maintenance therapy

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8
Q

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

A

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

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9
Q

Describe the adverse effects of azathioprine. (4)

A

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

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10
Q

Name two calcineurin inhibitors. (2)

Describe their MoA (2)

A

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

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11
Q

Describe the common uses for calcineurin inhibitors. (4)

A

Widely in transplants, atopic dermatitis, psoriasis.

Less common in rheumatology.

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12
Q

Describe the main ADR of calcineurin inhibitors. (2)

A

Renal toxicity. Need to monitor BP and eGFR regularly.

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13
Q

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

A

CYP450 metabolised

DDIs common.

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14
Q

Describe the MoA for mycophenolate mofetil. (4)

A

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.

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15
Q

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

A

Induction therapy in SLE and vasculits.

Takes 6 weeks to kick in fully.

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16
Q

Describe cyclophosphamide. (2)

A

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

17
Q

Describe indications for cyclophosphamide. (5)

A

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

18
Q

Give three important considerations when prescribing phosphamide. (6)

A

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.

19
Q

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

A

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

20
Q

Explain the method of administration on methotrexate. (3)

A

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

21
Q

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

A

Daily dosing - should always be given weekly.

22
Q

Describe the commonest DDI relating to methotrexate. (3)

A

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

23
Q

Describe the common ADRs of methotrexate. (4)

A

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

24
Q

Describe the MoA for corticosteriods in Immunosuppression. (2)

A

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

25
Q

Describe the Side effects of corticosteriods. (5)

A
Osteoporosis 
Cataracts
Diabetes
Glaucoma
Buffalo hump 
Similar to “old age”
26
Q

Describe sulphasalazine. (3)

A

Non-biological, non-immunosuppressant.

Anti-inflammatory and infection fighting portions - T cell inhibition, reduced neutrophil degranulation.

27
Q

Describe indications for sulphasalazine use. (4)

A

Poorly absorbed so used mostly in IBD.

Safe in pregnancy, few DDIs, doesn’t need monitoring.

28
Q

Describe hydrochloroquine. (4)

A

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

29
Q

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

A

Adalimumab

Infliximab

30
Q

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

A

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

31
Q

Describe Rituximab. (2)

Describe its indications for use. (4)

A

Monoclonal antibody that causes B cell apoptosis.

Used in RA, SLE, lymphoma and vasculitis.

32
Q

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

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