FB - Immunosuppressants Flashcards

1
Q

List TWO examples of immunosuppressant calcineurin inhibitors

A

Ciclosporin, tacrolimus

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2
Q

List TWO examples of immunosuppressant cytotoxic antimetabolites

A

Azathioprine, mycophenolate

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3
Q

Name an example of an immunosuppressant mTor inhibitor

A

Sirolimus

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4
Q

Name an example of a polyclonal antibody used for immunosuppression

A

Rabbit anti-thymocyte globulin

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5
Q

Name an example of a monoclonal antibody targetting the IL-2 receptor that suppresses T cell proliferation

A

Daclizumab

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6
Q

Name an anti-cytokine signalling monoclonal antibody targetting IL-2 receptors

A

Daclizumab

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7
Q

Name an immunosuppressant drug targetting S1P receptors

A

Fingolimod

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8
Q

Describe the mechanism of action of fingolimod

A

> Phosphorylated to active metabolite fingolimod‐P
Structurally similar to sphingosine1‐phosphate (S1P)
Potent S1P receptor agonist
Functional antagonist (likely through desensitizing S1P receptors or disrupting S1P signalling gradients)
Reduces lymphocyte egress from lymph nodes
Disrupts cytokine-mediate lymphocyte homing
Reduces circulating lymphocytes

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9
Q

What is the half-life of fingolimod?

A

Approximately 8 days

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10
Q

What is the major adverse effect of fingolimod?

A

“First-dose” negative cardiac chronotropic effects due to S1P1 and S1P3 activation in sinoatrial cells

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11
Q

Name an immunosuppressant drug derived from from Isaria sinclarii (cordyceps)

A

Fingolimod

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12
Q

What is the primary indication for fingolimod?

A

Multiple sclerosis

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13
Q

To which immunophilin does ciclosporin bind?

A

Cyclophilin

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14
Q

To which immunophilin do tacrolimus and sirolimus bind?

A

FKBP12

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15
Q

Explain the mechanism of action of sirolimus

A

> Binds the immunophilin FKBP12
Complex with FKBP12 inhibits mTor
Arrests cell cycle from G1 to S phase
Reduces cytokine‐mediated proliferation of T & B cells

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16
Q

Which is more potent, ciclosporin or tacrolimus?

A

Tacrolimus is 10x to 100x more potent that ciclosporin

17
Q

Explain the mechanisms of action of ciclosporin and tacrolimus

A

> Ciclosporin and tacrolimus bind immunophilins (cyclophilin and FKBP12, respectively)
Complex with immunophilin inhibits calcineurin (activated by T cell receptors)
Prevents dephosphorylation and nuclear translocation of NFAT
Prevents nuclear transcription of cytokine genes (e.g., IL-2, TNFalpha and IFNgamma)
Inhibits T cell proliferation (also proliferation of B cells and cytotoxic T-lymphocytes)

18
Q

List FOUR major adverse effects of cytotoxic antimetabolite immunosuppresant drugs

A

bonemarrow depression: leukopenia, anaemia,

thrombocytopenia, bleeding, GI toxicity, lymphoma, neoplasia

19
Q

List at least THREE targets of rabbit anti‐thymocyte globulin polyclonal antibody used as an immunosuppressant drug

A

Non‐selective purified IgG targeting T and B lymphocytes, NK cells, and MHC class I and II antigens, co‐stimulator molecules

20
Q

List FOUR mechanisms of action of rabbit anti‐thymocyte globulin polyclonal antibody used as an immunosuppressant drug

A

Mechanisms of action:
• opsonization and complement‐dependent cytotoxicity
• antibody‐dependent cell‐mediated cytotoxicity
• depletion of T lymphocytes
• cross‐link TCR leading to T cell anergy induction

21
Q

List FOUR side effects of rabbit anti‐thymocyte globulin polyclonal antibody used as an immunosuppressant drug

A

Side effects:
• 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