Anti-rheumatoid drugs

Question 1

Describe pathophysiology of RA

Answer 1

Either decrease of anti inflammatory or increase in pro inflammatory molecules
Leading to dissolution of articular cartilage and bone. Formation of a pannus (inflammatory cell infiltrate into synovium so fibrovascular layer over joint surface)

Question 2

Clinical features of RA

Answer 2

Early morning stiffness (>1 hour)
Symmetrical pain and swelling of small joints (at least 3)
Rheumatoid nodules
Hand deformities

Question 3

Immunosuppressants used to treat autoimmune disorders

Answer 3

Corticosteroids
Calcineurin inhibitors (tacrolimus and ciclosporin)
Azathioprine
Mycophenolate mofetil

Question 4

Examples of DMARDs

Answer 4

Methotrexate
Sulphasalazine
Anti-TNF
Rituximab
Cyclophosphamide

Question 5

MoA of corticosteroids

Answer 5

Inhibit T cell activation

Inhibit IL1 and IL6 (proinflammatory)

Question 6

Indications for azothioprine

Answer 6

SLE
IBD
Vasculitis

Question 7

What needs to be done prior to starting azathioprine

Answer 7

Test TPMT activity (metabolises azathioprine)

If lower activity need lower dose

Question 8

MoA of azathioprine

Answer 8

Steroid sparing drug

Cleaved to 6-MP which decreases DNA synthesis

Question 9

Side effects of azathioprine and what needs to be monitored

Answer 9

Bone marrow suppression - need to monitor FBC
Malignancy and infection risk
Hepatitis - need to monitor LFTs

Question 10

Indications for calcineurin inhibitors

Answer 10

Transplant
Atopic dermatitis
Psoriasis

Question 11

MoA of calcineurin inhibitors

Answer 11

Ciclosporin binds to cyclophilin
Tacrolimus binds to tacrolimus binding protein
Complexes bind to calcineurin which prevents calcineurin from activating T cell to start IL2 transcription

Question 12

Sided effects of calcineurin inhibitors and what needs monitoring

Answer 12

Nephrotoxic - monitor GFR and BP
Diarrhoea and vomiting
Hyperlipidaemia - monitor cholesterol

Question 13

Indications for MM

Answer 13

Transplant

Lupus nephritis

Question 14

MoA of MM

Answer 14

MPA (prodrug) inhibits inosine monophosphate dehydrogenase so prevents guanine synthesis
This impairs B and T cell proliferation

Question 15

Indications for methotrexate

Answer 15

RA
Malignancy
Psoriasis
Crohn’s

Question 16

Interactions of methotrexate

Answer 16

Highly protein bound so is displaced by NSAIDs

Question 17

Dose regimen of methotrexate

Answer 17

Weekly

Question 18

MoA of methotrexate in non-malignancy dose

Answer 18

Inhibits purine metabolism and increases adenosine which reduces T cell activation

Question 19

Contraindications for methotrexate

Answer 19

Chronic liver disease

Pregnancy

Question 20

MoA of methotrexate in malignancy dose

Answer 20

Inhibits DHFR so inhibits folate synthesis which is needed for DNA synthesis (S phase of cell cycle)
Has greater toxicity in rapidly dividing cells

Question 21

What needs to be done before starting methotrexate

Answer 21

LFTs
CXR
Pregnancy test if applicable

Question 22

Side effects of methotrexate

Answer 22

Mucositis in malignancy dose
Bone marrow suppression 
Hepatitis
Cirrhosis
Pneumonitis
Infection risk

Question 23

Indications for sulphasalazine

Answer 23

RA

IBD

Question 24

What is contained in sulphasalazine and why does this make it good for treating IBD

Answer 24

5-ASA (active part)

Sulfapyridine (poorly absorbed by gut so drug stays at site of action)

Question 25

MoA of sulphasalazine

Answer 25

Inhibits T cell proliferation Inhibits IL2 production Reduces neutrophil degranulation

Question 26

Side effects of sulphasalazine

Answer 26

``` Bone marrow suppression Hepatitis Rash Abdominal pain Nausea (Side effects usually last <8 weeks) ```

Question 27

What needs to be done prior to starting anti-TNF therapy

Answer 27

Latent TB screen

Question 28

MoA of anti-TNF

Answer 28

anti inflammatory Decreases angiogenesis Inhibits metalloproteinases so slows joint destruction

Question 29

Indications for rituximab

Answer 29

RA mainly SLE Vasculitis

Question 30

MoA of rituximab

Answer 30

Monoclonal antibody which binds to CD20 causing B cell apoptosis

Question 31

Indications for cyclophosphamide

Answer 31

Leukaemia Lymphomas Lupus nephritis ANCA vasculitis

Question 32

MoA of cyclophosphamide

Answer 32

Prodrug cleaved to 4-HC | Cross links DNA and suppresses B and T cell activity

Question 33

Side effects of cyclophosphamide

Answer 33

Bladder cancer Lymphoma Leukaemia Infertility (proportional to dose and age)

Question 34

What should be done before starting pre menopausal women on cyclophosphamide

Answer 34

Freeze eggs | Infertility counselling

Question 35

How does cyclophosphamide affect the bladder and what can prevent this

Answer 35

Acrolein is a cyclophosphamide metabolite which is toxic to bladder epithelium and causes haemorrhagic cystitis Prevent by high hydration and mesna (binds to acrolein)