Immunosuppressants Flashcards
Outline the aetiology of rheumatoid arthritis.
1% prevalence in UK
Onset at any age
Women more at risk than men
What are the X-ray changes associated with rheumatoid arthritis?
- soft tissue swelling
- periarticular osteoporosis (early) —> marginal bony erosion (late)
- narrowing of articular space
- articular destruction
- joint deformity
What are the pro-inflammatory factors associated with rheumatoid arthritis?
IL-1
IL-6 —> raised CRP
TNF-alpha
What are the joint deformities associated with rheumatoid arthritis?
Early RA
- dorsal tenosynovitis of wrist and small joints
- spindling of fingers
Ulnar deviation
Boutonnière’s deformity = fixed flexion of proximal IP
Swan-neck deformity = fixed hyperextension of proximal IP
How is rheumatoid arthritis treated? What is the aim of treatment?
Symptomatic relief + prevention of joint destruction (remission)
- early use of DMARDs (unless atypical presentation)
- achieve good disease control
- use adequate dosages (check for subclinical signs)
- avoid using long-term corticosteroids
What are DMARDs?
Disease-modifying anti-rheumatic drugs
Outline SLE
Inflammatory, multisystem autoimmune disorder
Causes arthralgia, rashes (classic malar butterfly rash), cerebral & renal disease
Outline vasculitis. What are the different subtypes?
Widespread vasculitis causing systemic symptoms and signs (systemic inflammatory vasculitides)
Large vessel e.g. giant cell arteritis, polymyalgia rheumatica
Medium vessel e.g. polyarteritis nodosa
Small vessel e.g. granulomatosis with polyangitis (Wegener’s granulomatosis), Henoch-Schönlein purpura, Behçet’s disease
What is the aim of treatment for vasculitis?
Symptomatic relief
Reduction in mortality —> induction of disease remission, then maintenance
Prevention of organ damage
Reduction in long-term morbidity caused by disease/drugs
How do corticosteroids act?
Prevent IL-1 & IL-6 production by macrophages
Inhibit stages of T-cell activation
—> reduce inflammation
Give some examples of ADRs associated with corticosteroids.
- weight gain
- fat redistribution
- striae
- growth retardation
- reduced wound healing
- hair thinning
- skin thinning & bruising
- osteoporosis
- avascular necrosis
- glucose intolerance —> hyperglycaemia
- adverse lipid profile
- increased infection risk
- increased cancer risk
- cataract formation & glaucoma
What are the indications for azathioprine? How does it work?
Indications:
- rheumatoid arthritis
- SLE & vasculitis (maintenance therapy)
- IBD
- bullous skin disease (pemphigus)
- atopic dermatitis
- “steroid sparing” drug
- transplantation
- leukaemia
Prodrug cleaved to active metabolite 6-mercaptopurine (6-MP)
Acts as anti-metabolite to decrease DNA & RNA synthesis
What are the pharmacodynamics of azathioprine?
6-MP metabolised by thiopurine methyltransferase (TPMT)
TPMT gene is highly polymorphic - those with low/absent TPMT levels are more likely to develop myelosuppression (lower dose given)
Test for TPMT activity before/immediately after prescribing
Give some examples of ADRs associated with azathioprine.
- bone marrow suppression (monitor FBC)
- increased risk of malignancy (particularly haematological)
- increased risk of infection
- hepatitis (monitor LFTs)
Give some examples of calcineurin inhibitors. How do they work? When are they indicated?
Ciclosporin (binds to cyclophilin protein)
Tacrolimus (binds to tacrolimus-binding protein)
Calcineurin exerts phosphatase activity on nuclear factor of activated T-cells —> migrates to nucleus to start IL-2 transcription —> inflammation
(therefore inhibiting calcineurin reduces inflammation)
Indications:
- transplantation
- psoriasis
- atopic dermatitis (topical formulation - Pimecrolimus)
- RA/SLE (useful, as no effect on bone marrow)