6.1 Immunosuppression and DMARDs Flashcards Preview

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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

11

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

28

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

What is anti-TNF alpha?

Anti-inflammatory
Decreases joint destruction
Decreases angiogenesis