Immunosuppressive drugs

Question 1

is azathioprine a drug or prodrug

Answer 1

prodrug (activated in the body)

Question 2

what should you not prescribe with azathioprine?

Answer 2

allopurinol because allopurinol inhibits xanthine oxidase, the enzyme that metabolises azathioprine. This leads to toxicity of azathioprine and bone suppression

Question 3

what are the SEs of azathioprine?

Answer 3

• Bone marrow suppression
• Anaemia 
• Nausea and vomiting
• Alopecia
Pancreatitis

Question 4

what is a characteristic of azathioprine that you need to consider?

Answer 4

carcinogen/teratogen

Question 5

what would you see in a patient who is on immunosuppressive drug?

Answer 5

may see signs such as ulcers as immunosuppressive drugs slow cell turnover. So you are worried about the mouth ulcers or mucositis, and GIT tract disturbances

Question 6

since immunosuppressive drugs suppress the bone marrow, what would you want to ask about?

Answer 6

platelet function, immunity and blood count.

Question 7

how would you ask about platelet function?

Answer 7

bleeding gums from brushing teeth, and epistaxis

Question 8

what skin infections might you see in immunocompromised patients?

Answer 8

boils, folliculitis, abscess

Question 9

what do we use methotrexate for?

Answer 9

RA, crohn’s, psoriasis, cancer

Question 10

what are the two types of calcineurin inhibitors? How do they work?

Answer 10

Cyclosporin and tacrolimus. They both inhibit IL2 production and action, consequently reducing Tcell proliferation

Question 11

SE of calcineurin inhibitors?

Answer 11

alopecia, tremor, hirustism, nephrotoxicity

Question 12

what do you need to monitor with tacrolimus?

Answer 12

BP
BSL
Potassium levels
Cholesterol levels
LFTs

Question 13

how do glucocorticoids mediate immunosuppression?

Answer 13

Glucocorticoids are immunosuppressant chiefly because, they restrain the clonal proliferation of Th cells, through decreasing transcription of the gene for IL-2. However, they also decrease the transcription of many other cytokine genes (including those for TNF-α, IFN-γ, IL-1 and many other interleukins) in both the induction and effector phases of the immune response. The synthesis and release of anti-inflammatory proteins (e.g. annexin 1, protease inhibitors, etc.) is also increased.

Question 14

prior to commencing immunosuppressive therapy- you would want to do a screen for TB. What Ix would you order?

Answer 14

Interferon gold and CXR

Question 15

SE of azathioprine (Imuran)?

Answer 15

Nausea, vomiting, rash, fever, pancreatitis, immunosuppression, photosensitivity, lymphoma

Question 16

in order to quality for Anti-TNF medication in the setting of IBD- what 3 criteria does the patient need to have?

Answer 16

1. Patient needs to be sick
2. Has been on Imuran 3 months
3. had a tapering course of steroids.

Question 17

how does rituximab work?

Answer 17

it is a monoclonal antibody to CD20 on B cells, thus destroying B cells.

Question 18

where does pulmonary fibrosis due to methotrexate occur in the lung

Answer 18

mid zones of the lung

Question 19

SE of methotrexate?

Answer 19

myelosuppression, nausea and vomiting (more frequent with high doses), oral mucositis, pulmonary toxicity, hepatotoxicity, rash, itch, urticaria, photosensitivity; neurotoxicity

Question 20

how does azathioprine work?

Answer 20

Impairs purine synthesis- hence interferes with DNA synthesis

Impairs lymphocyte production

Question 21

what are some practice points for methotrexate?

Answer 21

Contraindicated in severe infection such as latent TB

Dose adjust for renal impairment

Do not use in pregnancy/breast feeding

Often coadministered with folic acid to prevent blood dyscrasia

Question 22

how does mycophenolate work?

Answer 22

Suppresses lymphocyte proliferation by inhibiting iosine monophosphate dehydrogenase

Question 23

contraindications to infliximab?

Answer 23

Contraindicated in severe heart failure
Contraindicated in TB etc

Contraindicated in lymphoproliferative disorders

Question 24

what do we need to continually monitor when a patient is put on hydroxycloroquine?

Answer 24

it can cause ocular toxicity so need to conduct a basic visual exam before prescription and then monitor for any blurred vision.

contraindicated in retinopathy