Immunosuppression

Question 1

What clinical criteria is used to diagnose rheumatoid arthritis

Answer 1

Morning stiffness for >1hr 
Arthritis of > 3 joints 
Arthritis of hand joints
Symmetrical arthritis
Rheumatoid nodules
Serum rheumatoid factor 
Changes on an X-Ray

Question 2

What is SLE?

Answer 2

Systemic lupus erythematous

Multi-system disease causing a malar rash, usually affecting women of a child bearing age

Question 3

What is vasculitis and what are some typical characteristics seen with it

Answer 3

Vasculitis is a systemic disease affecting the vasculature. Typically have:
Leukocytes infiltrate
Fibrinoid necrosis
Thrombosis

Question 4

What are the functions of interleukins (brief)

Answer 4

IL-1 - fever
IL-2 - T-cell activation
IL-3 - bone marrow
IL-4 - IgE
IL-5 - IgA
IL-6 - pro-inflammatory actions

Question 5

Name some immunosuppressants

Answer 5

Corticosteroids
Azathioprine
Calcineurin inhibitors
Mycophenolate mofetil
Cyclophosphamide
Methotrexate
Sulfasalazine
Biologicals

Question 6

How do corticosteroids work?

Answer 6

Prevent IL-1 and Il-6 production from macrophages

Inhibit T-cell activation and affect all inflammatory cells to inhibit inflammatory actions

Question 7

Name some corticosteroids

Answer 7

Prednisolone
Betamethasone
Fludrocortisone
Hydrocortisone

Question 8

Name some side effects of corticosteroids

Answer 8

Side effects are features seen with old age, e.g.
Osteoporosis
Diabetes
Hypertension
Weight gain
Immunosuppression
Easy bruising
Increased risk of GI bleeding and perforation

Question 9

Name some adverse effects of immunosuppression

Answer 9

Bone marrow suppression - monitor FBC
Increased risk of malignancy
Increased risk of infection
Hepatitis
Nausea and vomiting

Question 10

Describe how azathioprine works to suppress the immune system

Answer 10

Azathioprine is cleaved to 6-MP which decreases DNA and RNA synthesis by inhibiting purine synthesis, this decreases inflammatory effects

Question 11

When is azathioprine used and what should be done before prescribing it and why

Answer 11

Azathioprine is used for SLE and vasculitis (also RA, IBD and steroid sparing drug)
Must test TPMT activity before prescribing as 6-MP is metabolised by TPMT which has a high degree of gene polymorphism - if TPMT levels low have risk of myelosuppression

Question 12

Describe how calcineurin inhibitors cause immunosuppression and when are they used

Answer 12

Calcineurin inhibitors are used after transplantation and for atopic dermatitis and psoriasis
They inhibit helper T-cells to prevent IL-2 production

Question 13

Name some calcineurin inhibitors

Answer 13

Cyclosporin

Tacrolimus

Question 14

Describe how mycophenolate mofetil works to cause immunosuppression and when it is used

Answer 14

Mycophenolate mofetil is used in transplantation, lupus nephritis, vasculitis
Is a prodrug that inhibits an enzyme required for guanosine synthesis to impair B and T cell proliferation

Question 15

Name some ADRs of MMF

Answer 15

Nausea
Vomiting
Diarrhoea
Myelosuppression

Question 16

Describe how cyclophosphamide works and when it is used

Answer 16

Cyclophosphamide is used for lymphoma, leukaemia, solid cancer, lupus nephritis, ANCA-vasculitis, RA
Works by cross-linking DNA so it cannot replicate and also suppresses T and B cell activity

Question 17

Name some risks associated with cyclophosphamide use

Answer 17

Bladder epithelium toxicity - acrolein is toxic to bladder epithelium and causes haemorrhagic cystitis
Increased risk of bladder cancer, lymphoma and leukaemia
Risk of infertility - under 25 negligible but over 30 risk is moderate

Question 18

What can be given to prevent haemorrhagic cystitis associated with cyclophosphamide use

Answer 18

Aggressive hydration

Use of Mensa - clears acrolein to prevent haemorrhagic cystitis

Question 19

Describe how methotrexate works and when is it used

Answer 19

Methotrexate is used for RA as well as malignancy, psoriasis, Crohn’s and ectopic pregnancy (abortion)
Methotrexate competitively inhibits dihydrofolate reductase to inhibit synthesis of DNA, RNA and proteins
Mechanism in non-malignant not well understood but have inhibition of adenosine accumulation which prevents T-cell activation

Question 20

Describe the pharmacokinetics of methotrexate

Answer 20

Low oral bioavailability but high intramuscular bioavailability
Dosing is weekly as has long t1/2
Excreted renally
Protein bound with NSAIDs displacing methotrexate from the protein

Question 21

Name some ADRs of methotrexate

Answer 21

Mucositis
Marrow suppression
Infertility - highly teratogenic 
Hepatitis
Cirrhosis
Pneumonitis
Infection risk

Question 22

Describe how sulfasalazine works and when it is used

Answer 22

Sulfasalazine is used to treat IBD as it has poor PO absorption
Works by inhibiting proliferation of T-cells and inhibits IL-2 production
Also reduces chemotaxis and degranulation of neutrophils

Question 23

Name some ADRs of sulfasalazine

Answer 23

Myelosuppression
Hepatitis
Rash
Nausea
Vomiting
Abdominal pain

Question 24

Describe the biopharmaceuticals used as immunosuppressants

Answer 24

Extracted from living systems and are highly specific
Use recombinant DNA technology to produce substances nearly identical to body’s key signalling molecules
Many of the molecules block TNF-alpha which causes decreased inflammation, decreased angiogenesis and decreased joint destruction

Question 25

What must be check for before a patient is started with anti-TNF therapy and why

Answer 25

Before anti-TNF treatment started, must screen for TB
There is a risk of TB reactivation with anti-TNF therapy as TNF-alpha is essential for development and maintenance of granulomas in TB

Question 26

Name a biopharmaceutical, describe how it works and what it is used for

Answer 26

Rituximab
Binds to CD20 on B-cell surfaces to cause B-cell apoptosis to prevent production of cytokines, antibodies and antigen presentation
Effective in RA