Immunosuppressants

Question 1

Calcineurin inhibitors?

Answer 1

Ciclosporin
Tacrolimus

Question 2

mTOR inhibitor name?

Answer 2

Sirolimus

Question 3

Cytotoxic antimetabolites names?

Answer 3

Azathioprine
Mycophenolate

Question 4

S1P receptor agonist name?

Answer 4

Fingolimod

Question 5

Polyclonal antibodies names?

Answer 5

Rabbit anti-thymocyte globulin

Question 6

Monoclonal antibodies?

Answer 6

Daclizumab
Infliximab
Mepolizumab

Question 7

Which combination is common?

Answer 7

Sirolimus + Ciclosporin

Question 8

Which class inhibits purine synthesis?

Answer 8

Cytotoxic antimetabolites - Azathioprine and Mycophenolate

Question 9

Triple therapy for renal transplant and various autoimmune disorders?

Answer 9

Calcineurin inhibitor (Ciclosporin/Tacrolimus)+ steroid + Azathioprine

Question 10

ADR of Sirolimus?

Answer 10

Hyperlipidemia
Thrombocytopenia
Hyperglycemia
Hypertension

Question 11

Which immunosuppressant to prevent arterial restenosis?

Answer 11

Sirolimus

Question 12

Uses of Calcineurin inhibitors in general?

Answer 12

Transplants of Kidney, pancreas, liver, heart
Uveitis
Rheumatoid Arthritis
Psoriasis

Question 13

Uses of Ciclosporin?

Answer 13

1st T-cell selective immunosuppressant
Lower rate of acute rejection and higher allograft survival
Has relatively lower bone marrow suppression

Question 14

Effects of Tacrolimus?

Answer 14

2nd T-cell selective immunosuppressant
10-100x more potent than Ciclosporin

Question 15

ADR of Calcineurin inhibitors?

Answer 15

Nephrotoxicity
Hyperglycaemia
Gum hyperplasia
Hyperlipidemia
Hypertension
Neurotoxicity

Question 16

Uses of Sirolimus?

Answer 16

Anti-proliferative and anti-angiogenic
Sirolimus-eluting coronary stents to prevent arterial re-stenosis

Question 17

MOA of Sirolimus?

Answer 17

Sirolimus:FKBP complex binds and inhibits mTOR.
Complex inhibits 70kDa S6 kinase + maintain repressor activity of 4E-BP1 + Arrest growth from G1 to S phase.
Inhibit cytokine-mediated proliferation of T & B cells.

Question 18

MOA of Azathioprine?

Answer 18

Drug is converted to 6-MP then converted to 6TG.
6TG impedes DNA synthesis as structural analogue/antimetabolite.
Inhibits de novo purine synthesis, lowering lymphocyte proliferation.

Question 19

Uses of Azathioprine?

Answer 19

Effective in renal transplant and various AI disorder using triple therapy

Question 20

ADR of Azathioprine?

Answer 20

Bone marrow depression = Leukopenia, anemia, thrombocytopenia, bleeding, GI toxicity, lymphoma, neoplasia etc etc

Question 21

MOA of Mycophenolate?

Answer 21

Mycophenolate Mofetil (MMF) and Mycophenolate Sodium (MPS) converted to mycophenolic acid - active metabolite
2. Inhibit de novo purine synthesis pathway by inhibiting IMPDH
3. More selective anti-proliferative effects for T/B cells
4. Suppress antibody formation by B cells

Question 22

Uses of Mycophenolate?

Answer 22

Inhibit recruitment of leukocytes to graft sites
Less BM suppression and GI toxicity than Azathioprine

Question 23

ADR of Mycophenolate?

Answer 23

Diarrhoea
Neutropenia
Anemia
Hypertension

Question 24

MOA of Fingolimod?

Answer 24

Phosphorylated to active metabolites Fingolimod-P.
Structurally similar to endogenous S1P, Fingolimod-P targets S1P receptor, activating S1P1, 3, 4 and 5.
S1P1 and S1P4 promote egress of lymphocytes from LNs and chemokine gradient-mediated lymphocyte homing.
Fingolimod-P can act as functional antagonist preventing lymphocyte egress from LN and lowering circulating lymphocytes.

Question 25

Uses of Fingolimod?

Answer 25

Multiple sclerosis

Question 26

ADR of Fingolimod?

Answer 26

1st dose negative cardiac chronotropic effects due to S1P1 and S1P3 activation in SA cells

Question 27

MOA of Rabbit anti-thymocyte globulin?

Answer 27

1. Polyclonal IgG - Thymoglobulin 2. Non-selective purified IgG targeting T & B Lymphocytes, NK cells, MHC 1&2 antigens, co-stimulator molecules etc. 1. Opsonization + Complement-dependent cytotoxicity 2. Ab-dependent cell-mediated cytotoxicity 3. Depletion of T lymphocytes 4. Cross-link TCR causing T cell anergy induction

Question 28

ADR of Rabbit anti-thymocyte globulin?

Answer 28

First-dose effect - cytokine release syndrome (fever, chill, hypotension) Thrombocytopenia / Leukopenia / Serum sickness Development of anti-foreign IgG antibodies Histiocytic lymphoma at site of injection

Question 29

Use of Daclizumab?

Answer 29

Suppress transplant rejection

Question 30

Use of Mepolizumab?

Answer 30

Severe asthma

Question 31

Use of Infliximab?

Answer 31

Rheumatoid Arthritis

Question 32

Use of Dupilumab?

Answer 32

Severe eczema

Question 33

Use of Belimumab?

Answer 33

SLE

Question 34

ADR of Daclizumab?

Answer 34

Anaphylaxis and serum sickness First dose flu-like syndrome Higher risk of infection/malignancies

Question 35

MOA of Calcineurin Inhibitors?

Answer 35

Bind to ubiquitous cytosolic immunophilin Cyclophilin/FKBP12 respectively. Cyclophilin/FKBP12 is a PPIase but functions as chaperone in immunosuppression. Complex binds and inhibits calcineurin. Prevent dephosphorylation and nuclear translocation of transcription factors: NF-AT. Inhibit cytokine gene transcription and synthesis. Inhibit primarily T cell proliferation, and B cells and CTL proliferation.