6.1 Immunosuppression and DMARDs Flashcards
What is Rheumatoid Arthritis?
A multisystem autoimmune disease
Causes joint deformities, CVS risk
Develops in the synovium, inflammation, proliferation then goes into cartilage and bone.
Due to an imbalance between pro/antiinflammatory cytokines
Which cytokines are involved in RA?
IL1
TNF Alpha
How do you diagnose RA?
X Rays
Morning Stiffness
Symmetrical
What is SLE?
Systemic Lupus Erythematosus
Systemic autoimmune disease
Butterfly rash
What is Vasculitis?
Inflammation that destroys blood vessels
Get pulmonary hemorrhages
Give examples of immunosuppressants?
Corticosteroids Azathrioprine DMARDs Ciclosporin and Tacrolimus Mycophenolate mofetil
What do ALL immunosuppressants do? (ADRs!!!)
Increase malignancy
Increase infection risk - FBC
Decrease bone marrow
How do Corticosteroids work?
It decreases the production of proinflammatory cytokines by macrophages and increases anti-inflammatory cytokines.
Restrains proliferation of T helper cells.
Receptor in cytoplasm -> Nucleus and change gene expression
ADRs of Steroids?
Weight Gain Purple Striae Osteoporosis Cataracts Cushings-like fat gain
How does Azathioprine work?
It is cleaved into 6MP which is an antimetabolite.
Inhibits purine synthesis to prevent DNA and RNA synthesis.
Metabolised by TPMT which is polymorphic
High levels –> Myelosuppression
Low –> Undertreatment
When do you use Azathioprine?
On what conditions?
Use to maintain a patient after treating them acutely with CS
IBD
Vasculitis
SLE
Dermatitis
What ADR can Azathioprine also cause?
Hepatitis - monitor LFTs
What type of drugs are Ciclosporin and Tacrolimus?
Calcineurin Inhibitors
Inhibit T helper cells by preventing IL2 production
When do you use calcineurin inhibitors?
Transplant
Atopic dermatitis
Psoriasis
Why is Ciclosporin particularly useful?
As it has no effect on bone marrow
Useful for RA and SLE
What are ADRs of Calcineurin Inhibitors?
Nephrotoxic (monitor eGFR)
Hypertension (monitor BP)
Hyperlipidaemia
GI- nausea, vomit, diarrhoea
When do you use MM?
In SLE
Transplant Medicine
What is MM?
Mycophenolate Mofetil is a prodrug which is converted to inhibit B and T cells
Prevents synthesis of guanine
Spares other rapidly dividing cells as they have measures against this
ADRs of MM?
GI
Myelosuppression
What is Cyclophosphamide?
Cytotoxic
Alkylating Agent
Suppresses B and T Cells
When do you use Cyclophosphamide?
Severe RA when all else fails Lymphoma Leukaemia SLE Wegeners Granulomas
ADRs of Cyclophosphamide
Very Toxic!!
Can induce cancers esp bladder cancer (void frequently)
Infertility
Teratogenic
NEED TO MONITOR FBC and adjust in renally impaired
What is a DMARD?
A disease modifying anti rheumatic drug
What are 3 examples of DMARDs?
Methotrexate
Sulphasalazine
Anti-TNF alpha agents
What is Methotrexate?
A folate antagonist
Gold Standard for RA treatment
Inhibits DHFR to prevent D/RNA and Protein synthesis
Best for rapidly dividing cells (active during S phase)
Why use Methotrexate?
It is well tolerated
Retained in the system
Only once a week (+Folic Acid)
Can improve efficacy of other DMARDs when used in conjunction
ADRs of Methotrexate?
Hepatitis, Cirrhosis
Infection Risk
Teratogenic
Aborts foetus’s
When can you use methotrexate?
RA
Malignancy
Crohns
Psoriasis
How do you monitor patients on methotrexate?
Chest X Ray FBC LFT U&E Creatinine
What is Suphasalazine a mix of?
5-ASA - anti-inflammatory, inhibits T cells and neutrophils
Sulphapyradine - fight infection
When do you use Sulphasalazine?
Safe for pregnant people
Good for IBD (Poorly absorbed so stays in the intestines)
ADRs for Sulphasalazine
Myelosuppression
Hepatitis
Rash
GI symptoms
Advantages of Sulphasalazine?
Safe for pregnancy Non-carcinogenic Has very few interactions Effective Less Toxic
When do you use anti-TNF agents?
If RA is clinically active
If other treatments have failed
Why don’t you use anti-TNF agents much?
Expensive
Can cause Hypersensitivity
Can cause infections
Hypogammaglobinaemia
What is anti-TNF alpha?
Anti-inflammatory
Decreases joint destruction
Decreases angiogenesis
