Immunosuppresion & disease modifying therapy Flashcards
What is rheumatoid arthritis?
Autoimmune multi-system disease
Inflammatory change and proliferation of synovium leading to dissolution of cartilage and bone
How is RA diagnosed?
Critical criteria:
- Morning stiffness >1 hour
- Arthritis of >3 joints
- Arthritis of hand and wrist joints
- smmetrical arthritis
- Rhematoid nodules
Non clinical criteria:
- serum rheumatoid factor/Anti CCP antibodies
- X-ray changes
What are the treatment goals for treating RA?
- Symptomatic relief
- Prevention of join destruction
What are the treatment goals for SLE and vasculitis?
- Symptomatic relief e.g arhralgia and Raynaud’s phenomenom
- Reduction in mortality
- Prevention of organ damage
- Reduction in long term morbidity caused by disease and by drugs
How do corticosteroids work as a DMARD?
- Prevent interleukin IL-1 and IL-6 production by macrophages
- Inhibit all stages of T cell activation
What are some of the side effects of corticosteroids?
- weight gain
- thrush
- immunosuppresion
- glaucoma
- cateracts
- blood glucose changes
- accelerates aging
- mood changes
- bruising
What is azathioprine used to treat?
- Maintenance therapy in SLE and vasculitis
- weak evidence of benefit in RA
- used in inflammatory bowel disease
How can effects of azothioprine differ between individuals?
- 6-MP metabolised by TPMT (thiopurine methyltransferase)
- TPMT gene highly polymorphic
- Individuals with low/ absent TPMT levels have risk of myelosuppression
- TPMT test done before prescribing
What is the mechanism of azathioprine?
- Azathioprine cleaved to 6 mercaptopurine (6-MP)
- Anti-metabolite decreases DNA and RNA synthesis
- Immune cells can’t go on to cause inflammatory response
What are some of the adverse effects of azathioprine treatment?
- Bone marrow suppression (monitor FBC)
- Increased risk of malignancy (true of all immunosuppressants)
- increased risk of infection
- hepatitis (monitor LFTs)
When are calcineurine inhibitors used in practice?
- Atopic dermatitis and Psoriasis
Name 2 calcineurin inhibitors
- Ciclosporin
- Tacrolimus
What is the MoA of ciclosporin and tacrolimus?
- Active against helper T cells - prevents production of IL-2 via calcineurin inhibition
- Ciclosporin- binds to cyclophilin protein
- Tacrolimus binds to tacrolimus binding protein
When is mycophenolate mofetil used in practice?
- primarily in transplanation
- good efficacy as induction and maintenance therapy for SLE and Vasculitis maintenance
What is the mechanism of action of mycophenolate mofetil?
- Pro-drug derived from fungus penicillum stoloniferum
- Inhibits inosin monophosphate dehydrogenase (required for guanosin synthesis
- Impairs B and T cell proliferation
- Spares other rapidly dividing cells