Immunosuppressants

Question 1

Steroids- ADRs? Short and long term?

Answer 1

Short term- Cushing’s syndrome, fluid retention, hypertension, skin atrophy, infections
Long term- HPA axis suppression, osteoporosis, avascular necrosis, glaucoma, cataracts

Question 2

Corticosteroids- mechanism?

Answer 2

Binds to steroid receptor, binds to DNA and switch on/off genes- inhibits B and T cell response, decrease production of pro-inflammatory cytokines (IL-1, IL-6)

Question 3

Azathioprine- mechanism and PKs?

Answer 3

Pro-drug, cleaved to active 6-MP, inhibits purine synthesis (antimetabolite), decreases DNA/RNA synthesis, INACTIVATED by TPMT

Question 4

Azathioprine- polymorphism??

Answer 4

Variation in TMPT levels- if absent/reduced -> increased risk of myelosuppression, if high levels-> reduced efficacy so… check levels before starting!

Question 5

Azathioprine- ADRs?

Answer 5

Bone marrow suppression, infection, hepatitis, cancer risk

Question 6

Azathioprine- uses?

Answer 6

RA, IBD, leukaemia, transplantation

Question 7

Cyclophosphamide- mechanism?

Answer 7

Alkylating agent, cross links DNA, prevents replication!

Question 8

Cyclophosphamide- ADRs?

Answer 8

Haemorrhaging cystitis! Bladder cancer! Infertility and teratogenesis! Lymphoma!

Question 9

Cyclophosphamide- uses?

Answer 9

Chemotherapy, wegener’s granulomatosis

Question 10

Mycophenolate mofetil (MMF) - mechanism?

Answer 10

Inhibits enzyme for guanosine synthesis, decreases ONLY B and T cell proliferation (other cells have other pathways!)

Question 11

MMF- ADRs?

Answer 11

Bone marrow suppression, infection, neutropenia, leukopenia

Question 12

MMF- uses?

Answer 12

Transplantation, lupus nephritis

Question 13

Calcineurin inhibitors- mechanism?

Answer 13

Drug-protein complex inhibits calcineurin, stops nuclear factor dephosphorylation -> decreased IL-2 synthesis

Question 14

Calcineurin inhibitors protein targets?

Answer 14

Tacrolimus- tacrolimus binding protein

Cyclosporin- cyclophillin protein

Question 15

Calcineurin inhibitors- ADRs?

Answer 15

Hypertension, nephrotoxicity, hyperlipidaemia,

Question 16

Calcineurin inhibitors- monitoring?

Answer 16

Blood pressure, eGFR

Question 17

Calcineurin inhibitors- uses?

Answer 17

Psoriasis, RA, transplant

Question 18

Sulphasalazine- mechanism?

Answer 18

Gut bacteria convert to 5-ASA -> decease inflammation, stays in gut. Unknown systemic mechanism- decreased T cells??

Question 19

Sulphasalazine- ADRs?

Answer 19

Nausea, bone marrow suppression, hepatitis, SAFE IN PREGNANCY

Question 20

Sulphasalazine- uses?

Answer 20

IBD, RA

Question 21

Methotrexate- mechanism?

Answer 21

Inhibits DHFR -> decreased purine and thymidine synthesis -> decreased DNA/RNA synthesis BUT DMARD mechanism NOT THIS! Decreased T cell activation?

Question 22

MTX- PKs?

Answer 22

WEEKLY dosing, oral/IM/SC

50% protein bound- NSAIDs displace!

Question 23

MTX- ADRs?

Answer 23

Bone marrow suppression, mucositis, hepatitis, cirrhosis, NOT SAFE IN PREGNANCY, reduced hepatic/renal function increases ADR risk!

Question 24

MTX- monitoring?

Answer 24

Baseline and monthly- FBCs, LFTs, U&Es, creatinine,

Initial CXR

Question 25

MTX- uses?

Answer 25

RA (gold standard!), psoriasis, crohn’s, malignancy

Question 26

Anti-TNF - mechanism?

Answer 26

Bind to TNF-a and inhibit interaction with TNF receptor! Decreases cytokines, angiogenesis, inflammation, joint destruction

Question 27

Anti-TNF - ADRs?

Answer 27

Malignancy, infection (TB!), skin infections

Question 28

Anti TNF monitoring?

Answer 28

Baseline and follow up- FBCs, LFTs, U&Es, creatinine,

Before treatment- CXR and TB screen