6.1 Immunosuppression and DMARDs

Question 1

What is Rheumatoid Arthritis?

Answer 1

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

Question 2

Which cytokines are involved in RA?

Answer 2

IL1

TNF Alpha

Question 3

How do you diagnose RA?

Answer 3

X Rays
Morning Stiffness
Symmetrical

Question 4

What is SLE?

Answer 4

Systemic Lupus Erythematosus
Systemic autoimmune disease
Butterfly rash

Question 5

What is Vasculitis?

Answer 5

Inflammation that destroys blood vessels

Get pulmonary hemorrhages

Question 6

Give examples of immunosuppressants?

Answer 6

Corticosteroids
Azathrioprine
DMARDs
Ciclosporin and Tacrolimus
Mycophenolate mofetil

Question 7

What do ALL immunosuppressants do? (ADRs!!!)

Answer 7

Increase malignancy
Increase infection risk - FBC
Decrease bone marrow

Question 8

How do Corticosteroids work?

Answer 8

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

Question 9

ADRs of Steroids?

Answer 9

Weight Gain
Purple Striae
Osteoporosis
Cataracts
Cushings-like fat gain

Question 10

How does Azathioprine work?

Answer 10

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

Question 11

When do you use Azathioprine?

On what conditions?

Answer 11

Use to maintain a patient after treating them acutely with CS

IBD
Vasculitis
SLE
Dermatitis

Question 12

What ADR can Azathioprine also cause?

Answer 12

Hepatitis - monitor LFTs

Question 13

What type of drugs are Ciclosporin and Tacrolimus?

Answer 13

Calcineurin Inhibitors

Inhibit T helper cells by preventing IL2 production

Question 14

When do you use calcineurin inhibitors?

Answer 14

Transplant
Atopic dermatitis
Psoriasis

Question 15

Why is Ciclosporin particularly useful?

Answer 15

As it has no effect on bone marrow

Useful for RA and SLE

Question 16

What are ADRs of Calcineurin Inhibitors?

Answer 16

Nephrotoxic (monitor eGFR)
Hypertension (monitor BP)
Hyperlipidaemia
GI- nausea, vomit, diarrhoea

Question 17

When do you use MM?

Answer 17

In SLE

Transplant Medicine

Question 18

What is MM?

Answer 18

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

Question 19

ADRs of MM?

Answer 19

GI

Myelosuppression

Question 20

What is Cyclophosphamide?

Answer 20

Cytotoxic
Alkylating Agent
Suppresses B and T Cells

Question 21

When do you use Cyclophosphamide?

Answer 21

Severe RA when all else fails
Lymphoma
Leukaemia
SLE
Wegeners Granulomas

Question 22

ADRs of Cyclophosphamide

Answer 22

Very Toxic!!
Can induce cancers esp bladder cancer (void frequently)
Infertility
Teratogenic
NEED TO MONITOR FBC and adjust in renally impaired

Question 23

What is a DMARD?

Answer 23

A disease modifying anti rheumatic drug

Question 24

What are 3 examples of DMARDs?

Answer 24

Methotrexate
Sulphasalazine
Anti-TNF alpha agents

Question 25

What is Methotrexate?

Answer 25

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)

Question 26

Why use Methotrexate?

Answer 26

It is well tolerated Retained in the system Only once a week (+Folic Acid) Can improve efficacy of other DMARDs when used in conjunction

Question 27

ADRs of Methotrexate?

Answer 27

Hepatitis, Cirrhosis Infection Risk Teratogenic Aborts foetus's

Question 28

When can you use methotrexate?

Answer 28

RA Malignancy Crohns Psoriasis

Question 29

How do you monitor patients on methotrexate?

Answer 29

``` Chest X Ray FBC LFT U&E Creatinine ```

Question 30

What is Suphasalazine a mix of?

Answer 30

5-ASA - anti-inflammatory, inhibits T cells and neutrophils | Sulphapyradine - fight infection

Question 31

When do you use Sulphasalazine?

Answer 31

Safe for pregnant people | Good for IBD (Poorly absorbed so stays in the intestines)

Question 32

ADRs for Sulphasalazine

Answer 32

Myelosuppression Hepatitis Rash GI symptoms

Question 33

Advantages of Sulphasalazine?

Answer 33

``` Safe for pregnancy Non-carcinogenic Has very few interactions Effective Less Toxic ```

Question 34

When do you use anti-TNF agents?

Answer 34

If RA is clinically active | If other treatments have failed

Question 35

Why don't you use anti-TNF agents much?

Answer 35

Expensive Can cause Hypersensitivity Can cause infections Hypogammaglobinaemia

Question 36

What is anti-TNF alpha?

Answer 36

Anti-inflammatory Decreases joint destruction Decreases angiogenesis