Immunosuppression

Question 1

What is the Pathogenesis of Rheumatoid Arthritis?

Answer 1

Pro inflammatory chemicals like T cells, IL-1 and IL-6
Outweigh
Anti-Inflammatory chemicals like IL-4 and B cells
This causes inflammation

Question 2

How do you diagnose Rheumatoid?

Answer 2

Morning stiffness for over an hour
Arthritis of 3 or more joints
Arthritis of hand joints
Nodules (advanced, shouldn’t get to this)

Question 3

What do Corticosteroids do?

Answer 3

Prevent IL-1 and 6 production by macrophages

Inhibit all stages of T cell activation

Question 4

What are ADRs of Corticosteroids?

Answer 4

Weight gain
Striae
Glucose intolerance
Osteoporosis

Question 5

What is Rheumatoid Arthritis?

Answer 5

Auto immune multi system disease

Inflammation in the joints

Question 6

Which conditions is Azathioprine used for?

Answer 6

SLE
Vasculitis
Inflammatory bowel disease
Bullous skin disease

Question 7

What is the mechanism of Azathioprine?

Answer 7

Cleaved to 6-MP

Works as an anti-metabolite to decrease DNA and RNA synthesis

Question 8

What should you be careful of with Azathioprine?

Answer 8

Those with low or absent TPMT gene levels are likely to develop myelosuppression
Myelosuppression is a decrease in leucocytes, erythrocytes and thrombocytes

Question 9

What are the ADRs of Azathioprine?

Answer 9

Bone marrow suppression
Increased risk of malignancy
Increased risk of infection

Question 10

What do Ciclosporins and Tacrolimus do?

Answer 10

Work against T helper cells

Prevent IL-2 production using calceurin inhibition

Question 11

What conditions are Calcineurin inhibitors used in?

Answer 11

Atopic dermatitis

Psoriasis

Question 12

What are the ADRs of Calcineurin inhibitors?

Answer 12

Nephrotoxicity
Hypertension
Hyperlipidaemia

Question 13

How does Mycophenolate Mofetil work?

Answer 13

Inhibit enzyme that is required for guanosine synthesis

Impairs B and T cell proliferation

Question 14

What are the ADRs of Mycophenolate Mofetil?

Answer 14

Nausea and vomiting

Myelosuppression

Question 15

What is Methotrexate the gold standard for?

Answer 15

Rheumatoid Arthritis

Question 16

What is the mechanism of action of methotrexate?

Answer 16

Inhibits enzymes involved in purine production
Accumulation of adenosine
Interacts with GPCRs on inflammatory cells to regulate their function
Also inhibits T cell activation

Question 17

What is important about dosing of Methotrexate?

Answer 17

Must be given weekly (NOT DAILY)

Question 18

What are ADRs of Methotrexate?

Answer 18

Mucositis
Marrow Suppression
Very teratogenic

Question 19

What do you need to make sure you do with patients who take Methotrexate?

Answer 19

Toxicity monitoring
Chest X rays
FBC, LFT, U&E, creatinine

Question 20

What are the effects of Sulfasalazine?

Answer 20

Inhibition of T cell proliferation by:

• Inhibition of IL-2 production
• T cell apoptosis
• inhibition of proliferation

Decreases chemotaxis and degranulation of neutrophils

Question 21

What are the ADRs of Sulfasalazine?

Answer 21

Myelosuppression
Hepatitis
Rash

Question 22

What are the actions of Rituximab?

Answer 22

Binds specifically to surface marker CD20

Deplete B cells

Question 23

What are inducers of Cytochrome CYP450?

Answer 23

Rifampicin
Carbamezepine
Phenytoin
Omeprazole

Question 24

What are some inhibitors of Cytochrome CYP450?

Answer 24

Ciprofloxacin
Antifungals
Paroxetine
Fluoxetine