8. Immunosuppression Flashcards
What is the clinical criteria for diagnosing RA?
Morning stiffness >1hour Arthritis >3joints Arthritis of hand joints Symmetrical arthritis Rheumatoid nodules
What is the non-clinical criteria to diagnose RA?
Serum rheumatoid factor/anti-CCP antibodies
X-ray changes
Name some immunosuppressants
Corticosteroids Methotrexate Azathioprine Ciclosporin Tacrolimus Mycophenolate mofetil Leflunomide Cyclophosphamide
What is the mechanism of action of corticosteroids?
Prevent interleukin IL-1 and IL-6 production by macrophages
Inhibit all stages of T-cell activation
What is azathioprine used for?
SLE and vasculitis - as maintenance therapy
IBD
Atopic dermatitis
Bullous skin disease
Many other uses as ‘steroid sparing’ drug
What should be done before prescribing azathioprine?
Test TPMT activity (thiopurine methyltransferase)
What are the ADR to azathioprine?
Bone marrow suppression
Increased risk of malignancy
Increased risk of infection
Hepatitis
Name some calcineurin inhibitors
Ciclosporin
Tacrolimus
When are ciclosporin and tacrolimus used?
Transplantation
Atopic dermatitis and psoriasis
What is the mechanism of action of calcineurim inhibitors?
Active against helper T-cells, preventing production of IL-2 via calcineurim inhibition
Ciclosporin binds to cyclophilin protein
Tacrolimus binds to tacrolimus-binding protein
When is mycophenolate mofetil used?
Primarily in transplantation
Good efficacy as induction and maintenance therapy for lupus nephritis/vasculitis maintenance
What is the mechanism of action of mycophenolate mofetil?
Prodrug
Inhibits inosine monophopshate dehydrogenase (IMD) - required for guanosine synthesis
Impairs B and T cell proliferation
Spares other rapidly dividing cells
What are the ADR with mycophenolate mofetil?
Nausea, vomiting, diarrhoea
What is the mechanism of action of cyclophosphamide?
Cross links DNA so that is cannot replicate
Suppresses T and B cell activity
What are the indications of cyclophosphamide?
Lymphoma, leukaemia, solid cancers
Lupus nephritis
Wegener’s granulomatosis
What are the ADR of cyclophosphamide?
Increased risk of bladder cancer, lymphoma and leukaemia
Infertility
Monitor FBC and adjust dose in renal impairment
What are the indications for methotrexate?
RA
Malignancy
Psoriasis
Crohn’s disease
What is the mechanism of action of methotrexate in cancer?
Competitively and reversible inhibits dihydrofolate reductase
Therefore inhibits the synthesis of DNA, RNA and proteins
What are the adverse effects of methotrexate?
Mucositis Marrow suppression Hepatitis Cirrhosis Pneumonitis Inferior risk Highly teratogenic, abortifacient
What is sulfasalazine used for?
RA
IBD
What are the immunological effects of sulfasalazine?
T cell inhibition of proliferation
Possible T cell apoptosis
Inhibition of IL-2 production
Neutrophil reduced chemotaxis and reduced degranulation
What are the adverse effects of sulfasalazine?
Myelosuppression Hepatitis Rash Nausea Abdo pain/vomiting
What is rituximab used for?
RA
Lupus
Vasculitis
What does rituximab cause?
B cell apoptosis
