Flashcards in 6.1 Immunosuppression and DMARDs Deck (36):
1
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
2
Which cytokines are involved in RA?
IL1
TNF Alpha
3
How do you diagnose RA?
X Rays
Morning Stiffness
Symmetrical
4
What is SLE?
Systemic Lupus Erythematosus
Systemic autoimmune disease
Butterfly rash
5
What is Vasculitis?
Inflammation that destroys blood vessels
Get pulmonary hemorrhages
6
Give examples of immunosuppressants?
Corticosteroids
Azathrioprine
DMARDs
Ciclosporin and Tacrolimus
Mycophenolate mofetil
7
What do ALL immunosuppressants do? (ADRs!!!)
Increase malignancy
Increase infection risk - FBC
Decrease bone marrow
8
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
9
ADRs of Steroids?
Weight Gain
Purple Striae
Osteoporosis
Cataracts
Cushings-like fat gain
10
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
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When do you use Azathioprine?
On what conditions?
Use to maintain a patient after treating them acutely with CS
IBD
Vasculitis
SLE
Dermatitis
12
What ADR can Azathioprine also cause?
Hepatitis - monitor LFTs
13
What type of drugs are Ciclosporin and Tacrolimus?
Calcineurin Inhibitors
Inhibit T helper cells by preventing IL2 production
14
When do you use calcineurin inhibitors?
Transplant
Atopic dermatitis
Psoriasis
15
Why is Ciclosporin particularly useful?
As it has no effect on bone marrow
Useful for RA and SLE
16
What are ADRs of Calcineurin Inhibitors?
Nephrotoxic (monitor eGFR)
Hypertension (monitor BP)
Hyperlipidaemia
GI- nausea, vomit, diarrhoea
17
When do you use MM?
In SLE
Transplant Medicine
18
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
19
ADRs of MM?
GI
Myelosuppression
20
What is Cyclophosphamide?
Cytotoxic
Alkylating Agent
Suppresses B and T Cells
21
When do you use Cyclophosphamide?
Severe RA when all else fails
Lymphoma
Leukaemia
SLE
Wegeners Granulomas
22
ADRs of Cyclophosphamide
Very Toxic!!
Can induce cancers esp bladder cancer (void frequently)
Infertility
Teratogenic
NEED TO MONITOR FBC and adjust in renally impaired
23
What is a DMARD?
A disease modifying anti rheumatic drug
24
What are 3 examples of DMARDs?
Methotrexate
Sulphasalazine
Anti-TNF alpha agents
25
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)
26
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
27
ADRs of Methotrexate?
Hepatitis, Cirrhosis
Infection Risk
Teratogenic
Aborts foetus's
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When can you use methotrexate?
RA
Malignancy
Crohns
Psoriasis
29
How do you monitor patients on methotrexate?
Chest X Ray
FBC
LFT
U&E
Creatinine
30
What is Suphasalazine a mix of?
5-ASA - anti-inflammatory, inhibits T cells and neutrophils
Sulphapyradine - fight infection
31
When do you use Sulphasalazine?
Safe for pregnant people
Good for IBD (Poorly absorbed so stays in the intestines)
32
ADRs for Sulphasalazine
Myelosuppression
Hepatitis
Rash
GI symptoms
33
Advantages of Sulphasalazine?
Safe for pregnancy
Non-carcinogenic
Has very few interactions
Effective
Less Toxic
34
When do you use anti-TNF agents?
If RA is clinically active
If other treatments have failed
35
Why don't you use anti-TNF agents much?
Expensive
Can cause Hypersensitivity
Can cause infections
Hypogammaglobinaemia
36