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Pharm > Immunosuppressants > Flashcards

Immunosuppressants Flashcards

1
Q

Calcineurin inhibitors?

A

Ciclosporin
Tacrolimus

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2
Q

mTOR inhibitor name?

A

Sirolimus

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3
Q

Cytotoxic antimetabolites names?

A

Azathioprine
Mycophenolate

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4
Q

S1P receptor agonist name?

A

Fingolimod

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5
Q

Polyclonal antibodies names?

A

Rabbit anti-thymocyte globulin

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6
Q

Monoclonal antibodies?

A

Daclizumab
Infliximab
Mepolizumab

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7
Q

Which combination is common?

A

Sirolimus + Ciclosporin

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8
Q

Which class inhibits purine synthesis?

A

Cytotoxic antimetabolites - Azathioprine and Mycophenolate

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9
Q

Triple therapy for renal transplant and various autoimmune disorders?

A

Calcineurin inhibitor (Ciclosporin/Tacrolimus)+ steroid + Azathioprine

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10
Q

ADR of Sirolimus?

A

Hyperlipidemia
Thrombocytopenia
Hyperglycemia
Hypertension

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11
Q

Which immunosuppressant to prevent arterial restenosis?

A

Sirolimus

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12
Q

Uses of Calcineurin inhibitors in general?

A

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

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13
Q

Uses of Ciclosporin?

A

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

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14
Q

Effects of Tacrolimus?

A

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

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15
Q

ADR of Calcineurin inhibitors?

A

Nephrotoxicity
Hyperglycaemia
Gum hyperplasia
Hyperlipidemia
Hypertension
Neurotoxicity

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16
Q

Uses of Sirolimus?

A

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

17
Q

MOA of Sirolimus?

A

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.

18
Q

MOA of Azathioprine?

A

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.

19
Q

Uses of Azathioprine?

A

Effective in renal transplant and various AI disorder using triple therapy

20
Q

ADR of Azathioprine?

A

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

21
Q

MOA of Mycophenolate?

A

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

22
Q

Uses of Mycophenolate?

A

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

23
Q

ADR of Mycophenolate?

A

Diarrhoea
Neutropenia
Anemia
Hypertension

24
Q

MOA of Fingolimod?

A

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.

25
Q

Uses of Fingolimod?

A

Multiple sclerosis

26
Q

ADR of Fingolimod?

A

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

27
Q

MOA of Rabbit anti-thymocyte globulin?

A
  1. Polyclonal IgG - Thymoglobulin
  2. Non-selective purified IgG targeting T & B Lymphocytes, NK cells, MHC 1&2 antigens, co-stimulator molecules etc.
  3. Opsonization + Complement-dependent cytotoxicity
  4. Ab-dependent cell-mediated cytotoxicity
  5. Depletion of T lymphocytes
  6. Cross-link TCR causing T cell anergy induction
28
Q

ADR of Rabbit anti-thymocyte globulin?

A

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

29
Q

Use of Daclizumab?

A

Suppress transplant rejection

30
Q

Use of Mepolizumab?

A

Severe asthma

31
Q

Use of Infliximab?

A

Rheumatoid Arthritis

32
Q

Use of Dupilumab?

A

Severe eczema

33
Q

Use of Belimumab?

34
Q

ADR of Daclizumab?

A

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

35
Q

MOA of Calcineurin Inhibitors?

A

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.

Pharm (20 decks)

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