Immunosuppression Flashcards
What clinical criteria is used to diagnose rheumatoid arthritis
Morning stiffness for >1hr Arthritis of > 3 joints Arthritis of hand joints Symmetrical arthritis Rheumatoid nodules Serum rheumatoid factor Changes on an X-Ray
What is SLE?
Systemic lupus erythematous
Multi-system disease causing a malar rash, usually affecting women of a child bearing age
What is vasculitis and what are some typical characteristics seen with it
Vasculitis is a systemic disease affecting the vasculature. Typically have:
Leukocytes infiltrate
Fibrinoid necrosis
Thrombosis
What are the functions of interleukins (brief)
IL-1 - fever IL-2 - T-cell activation IL-3 - bone marrow IL-4 - IgE IL-5 - IgA IL-6 - pro-inflammatory actions
Name some immunosuppressants
Corticosteroids Azathioprine Calcineurin inhibitors Mycophenolate mofetil Cyclophosphamide Methotrexate Sulfasalazine Biologicals
How do corticosteroids work?
Prevent IL-1 and Il-6 production from macrophages
Inhibit T-cell activation and affect all inflammatory cells to inhibit inflammatory actions
Name some corticosteroids
Prednisolone
Betamethasone
Fludrocortisone
Hydrocortisone
Name some side effects of corticosteroids
Side effects are features seen with old age, e.g. Osteoporosis Diabetes Hypertension Weight gain Immunosuppression Easy bruising Increased risk of GI bleeding and perforation
Name some adverse effects of immunosuppression
Bone marrow suppression - monitor FBC Increased risk of malignancy Increased risk of infection Hepatitis Nausea and vomiting
Describe how azathioprine works to suppress the immune system
Azathioprine is cleaved to 6-MP which decreases DNA and RNA synthesis by inhibiting purine synthesis, this decreases inflammatory effects
When is azathioprine used and what should be done before prescribing it and why
Azathioprine is used for SLE and vasculitis (also RA, IBD and steroid sparing drug)
Must test TPMT activity before prescribing as 6-MP is metabolised by TPMT which has a high degree of gene polymorphism - if TPMT levels low have risk of myelosuppression
Describe how calcineurin inhibitors cause immunosuppression and when are they used
Calcineurin inhibitors are used after transplantation and for atopic dermatitis and psoriasis
They inhibit helper T-cells to prevent IL-2 production
Name some calcineurin inhibitors
Cyclosporin
Tacrolimus
Describe how mycophenolate mofetil works to cause immunosuppression and when it is used
Mycophenolate mofetil is used in transplantation, lupus nephritis, vasculitis
Is a prodrug that inhibits an enzyme required for guanosine synthesis to impair B and T cell proliferation
Name some ADRs of MMF
Nausea
Vomiting
Diarrhoea
Myelosuppression
Describe how cyclophosphamide works and when it is used
Cyclophosphamide is used for lymphoma, leukaemia, solid cancer, lupus nephritis, ANCA-vasculitis, RA
Works by cross-linking DNA so it cannot replicate and also suppresses T and B cell activity
Name some risks associated with cyclophosphamide use
Bladder epithelium toxicity - acrolein is toxic to bladder epithelium and causes haemorrhagic cystitis
Increased risk of bladder cancer, lymphoma and leukaemia
Risk of infertility - under 25 negligible but over 30 risk is moderate
What can be given to prevent haemorrhagic cystitis associated with cyclophosphamide use
Aggressive hydration
Use of Mensa - clears acrolein to prevent haemorrhagic cystitis
Describe how methotrexate works and when is it used
Methotrexate is used for RA as well as malignancy, psoriasis, Crohn’s and ectopic pregnancy (abortion)
Methotrexate competitively inhibits dihydrofolate reductase to inhibit synthesis of DNA, RNA and proteins
Mechanism in non-malignant not well understood but have inhibition of adenosine accumulation which prevents T-cell activation
Describe the pharmacokinetics of methotrexate
Low oral bioavailability but high intramuscular bioavailability
Dosing is weekly as has long t1/2
Excreted renally
Protein bound with NSAIDs displacing methotrexate from the protein
Name some ADRs of methotrexate
Mucositis Marrow suppression Infertility - highly teratogenic Hepatitis Cirrhosis Pneumonitis Infection risk
Describe how sulfasalazine works and when it is used
Sulfasalazine is used to treat IBD as it has poor PO absorption
Works by inhibiting proliferation of T-cells and inhibits IL-2 production
Also reduces chemotaxis and degranulation of neutrophils
Name some ADRs of sulfasalazine
Myelosuppression Hepatitis Rash Nausea Vomiting Abdominal pain
Describe the biopharmaceuticals used as immunosuppressants
Extracted from living systems and are highly specific
Use recombinant DNA technology to produce substances nearly identical to body’s key signalling molecules
Many of the molecules block TNF-alpha which causes decreased inflammation, decreased angiogenesis and decreased joint destruction
What must be check for before a patient is started with anti-TNF therapy and why
Before anti-TNF treatment started, must screen for TB
There is a risk of TB reactivation with anti-TNF therapy as TNF-alpha is essential for development and maintenance of granulomas in TB
Name a biopharmaceutical, describe how it works and what it is used for
Rituximab
Binds to CD20 on B-cell surfaces to cause B-cell apoptosis to prevent production of cytokines, antibodies and antigen presentation
Effective in RA
