Immunosuppression Flashcards
Describe Rheumatoid Arthritis. (3)
An autoimmune inflammatory condition initially localised to the synovium before spreading to the dissolution of bone and cartilage.
Describe the causes of RA. (2)
Increased amount of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) compared to anti-inflammatory ones.
Describe the symptoms of RA. (5)
Morning stiffness for over an hour Swelling of over 3 joints Rheumatic nodules Serum rheumatoid factor or anti-CCP antibodies X Ray changes
Describe the treatment goals of RA. (2)
Relieve symptoms
Prevent joint destruction
Describe the treatment goals for SLE and vasculitis. (3)
Relieve symptoms
Reduce mortality
Prevent organ damage from disease process or therapies
Describe the MoA of azathioprine. (2)
Antiproliferative immunosuppressant - interferes with DNA / RNA synthesis.
Describe the use of azathioprine. (3)
SLE
Vasculitis
IBD as maintenance therapy
Describe the consideration that need to be made when prescribing azathioprine. (3)
It is metabolised by the TPMT gene, which is highly polymorphic, so just test TPMT levels before prescribing.
Describe the adverse effects of azathioprine. (4)
Bone marrow suppression - monitor FBC
Increased risk of malignancy esp in transplant
Increased risk of infection
Hepatitis - monitor LFTs
Name two calcineurin inhibitors. (2)
Describe their MoA (2)
Ciclosporin
Tacrolimus
Inhibits calcineurin, which normally activates T cells through IL-2
Describe the common uses for calcineurin inhibitors. (4)
Widely in transplants, atopic dermatitis, psoriasis.
Less common in rheumatology.
Describe the main ADR of calcineurin inhibitors. (2)
Renal toxicity. Need to monitor BP and eGFR regularly.
Describe the metabolism of calcineurin inhibitors, and why this is important. (2)
CYP450 metabolised
DDIs common.
Describe the MoA for mycophenolate mofetil. (4)
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.
Describe the common uses for mycophenolate mofetil. Explain why is might not be first choice. (3)
Induction therapy in SLE and vasculits.
Takes 6 weeks to kick in fully.
Describe cyclophosphamide. (2)
An alkylating agent that forms cross links in DNA, especially active in T and B cells.
Describe indications for cyclophosphamide. (5)
Lymphoma, leukaemia, solid cancers, lupus nephritis, ANCA-vasculitis.
Give three important considerations when prescribing phosphamide. (6)
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.
Describe the MoA of methotrexate in its common indications. (8)
Malignancy - inhibits dihydrofolate reductase to impair DNA and RNA synthesis.
RA / Crohns / psoriasis / vasculitis - T cell activation inhibition.
Explain the method of administration on methotrexate. (3)
Low oral bioavailability and common N+V when given oral so often given SubCut.
Describe the never event relating to methotrexate prescribing. (2)
Daily dosing - should always be given weekly.
Describe the commonest DDI relating to methotrexate. (3)
Can’t be taken with NSAIDs - fall in GFR can raise blood levels of methotrexate quickly to toxic levels.
Describe the common ADRs of methotrexate. (4)
Mucositis
Marrow suppression - infection risk
Hepatitis and cirrhosis
Highly teratogenic and abortifascient
Describe the MoA for corticosteriods in Immunosuppression. (2)
Prevents IL-1 and IL-6 Production by macrophages to inhibit all stages of T cell activation.
Describe the Side effects of corticosteriods. (5)
Osteoporosis Cataracts Diabetes Glaucoma Buffalo hump Similar to “old age”
Describe sulphasalazine. (3)
Non-biological, non-immunosuppressant.
Anti-inflammatory and infection fighting portions - T cell inhibition, reduced neutrophil degranulation.
Describe indications for sulphasalazine use. (4)
Poorly absorbed so used mostly in IBD.
Safe in pregnancy, few DDIs, doesn’t need monitoring.
Describe hydrochloroquine. (4)
Increases pH inside macrophage lysosomes. Non-immunosuppressant.
Used primarily for malaria, but also RA, vasculitis, SLE.
Name two monoclonal antibodies that block TNF-alpha. (2)
Adalimumab
Infliximab
Describe the effects of blocking TMF-alpha and three indications for doing so. (6)
Reduced inflammation, reduced joint destruction and reduced angiogenesis.
RA, psoriasis, IBD.
Describe Rituximab. (2)
Describe its indications for use. (4)
Monoclonal antibody that causes B cell apoptosis.
Used in RA, SLE, lymphoma and vasculitis.
Describe the functions of interleukins 1-5. (5)
1 - hot - fever 2 - T - increases T cell 3 - bone - stimulates bone marrow 4 - E - IgE 5 - A - IgA Hot T Bone stEAk.
