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AI Exam 2 > Transplant > Flashcards

Transplant Flashcards

1
Q

What is the major histocompatibility complex (MHC)?

A

MHC is a set of genes that produce molecules important for the immune system to recognise foreign substances

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2
Q

What are histocompatibility antigens?

A

Specific proteins that can cause an immune response leading to rejection of transplanted organs or tissues

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3
Q

What is the human leukocyte antigen (HLA)?

A

HLS is the human version of MHC, which helps the immune system distinguish between self and non-self

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4
Q

What is the biggest barrier to a transplant?

A

The recipient immune system

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5
Q

What is a Xenograft and chances of rejection?

A

A transplant between difference species, greatest immune response = rejection

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6
Q

What is a Autograft and chances of rejection?

A

From one part of the body to another on the same individual = no rejection

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7
Q

What is a Isograft and chances of rejection?

A

Grafts between genetically identical individuals = no rejection

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8
Q

What is a Allograft and chances of rejection?

A

Between members of the same species, response varies depending on histocompatibility of donor and recipient but also organ type.

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9
Q

What cells are central in the rejection of grafts?

A

T Cells

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10
Q

What are the 4 security checkpoints of rejection?

A

1) Security spots an unknown visitor (foreign craft)
2) Security checks the visitor’s badge (MHC-antigen interaction)
3) Visitor gets a pat-down (co-stimulatory interaction) to ensure they aren’t a threat, setting off alarms if they are (activation of pathways)
4) If the alarms go off, backup (T cell proliferation) is called in to handle the situation (growth signals)

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11
Q

What is HLA compatibility?

A

A way to minimise / control the host immune response

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12
Q

What happens if HLA compatibility is poor?

A

Rejection chances increase, need to match HLA as best as we can!

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13
Q

What are the benefits of HLA-compatibility?

A

-Better graft function
-Fewer episodes of rejection
-Longer graft survival
-Reduced immunosuppression
-Decreased risk of sensitisation increasing issues with further transplants if required

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14
Q

What are the two phases of immunosuppression?

A

Induction and maintenance

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15
Q

What medication’s are involved in the induction phase of immunosuppression?*Transplant

A

Corticosteroids, Basiliximab, Alemtuzumab, Antithymocyte globulin (ATG)

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16
Q

What medications are involved in maintenance therapy post transplant?

A

Calcineurin Inhibitors, Antiproliferative drugs, Corticosteroids, mTOR inhibitors,

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17
Q

Examples of Calcineurin Inhibitors?

A

Ciclosporin, Tacrolimus

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18
Q

Do Calcineurin Inhibitors need to be brand specific?

A

YES

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19
Q

What is the difference in bioavailability for cyclosporin oral vs IV?

A

Oral cyclosporin dose is approximately 3 times the IV dose.

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20
Q

What is the difference in bioavailability for Tacrolimus oral vs IV?

A

Oral dose of tacrolimus is approximately 3-5 times the IV dose

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21
Q

What are some Concentration related side effects of Ciclosporin and Tacrolimus?

A

Nephrotoxicity, hypertension, hyperlipidaemia, gingival hyperplasia, hirsutism, tremor.

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22
Q

What drug do 5% of people taking get diabetes?

A

Ciclosporin

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23
Q

What is the trough level of Ciclosporin?

A

100-300ng/ml

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24
Q

Neoral is a brand example of what drug?

A

Ciclosporin

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25
Q

If a patient on ciclosporin has uncontrolled hypertension, what should we do?

A

Stop ciclosporin!

26
Q

What is Ciclosporin?

A

Fungal Metabolite

27
Q

What is tacrolimus?

A

Macrolide antibiotic

28
Q

What is the difference between Tacrolimus and Ciclosporin?

A

Tacrolimus is more potent!

29
Q

What is the trough level of Tacrolimus?

A

5-15ng/ml

30
Q

Is Tacrolimus and Sirolimus metabolised by CYP450 enzymes?

A

Yes = Numerous interactions!!

31
Q

What are some examples of antiproliferative drugs?

A

Azathioprine, Metcaptopurine, Mycophenolate

32
Q

What are the main side effects of Azathioprine?

A

Haematological
N&V!

33
Q

What does Azathioprine severely interact with and what should we do?

A

Allopurinol - reduce Azathioprine dose to 1/4!

34
Q

Out of mycophenolate and Azathioprine, which drug is the most patient?

A

Mycophenolate

35
Q

Main side effects of Mycophenolate?

A

-Haematological, neutropenia, leukopenia, mild anaemia,
-GI side effects which can be dose limiting,

36
Q

What can be given if someone is having diarrhoea when taking Mycophenolate?

A

Enteric coated - ‘Myfortic’

37
Q

What is the Mycophenolate levels decreased by?

A

Antacids, Iron, Rifamacin.

38
Q

What is the Mycophenolate level increased by?

A

Aciclovir and Ganciclovir

39
Q

What is the initial phase of dosage for Balatacept?

A

IV on DAY 1 and DAY 5, and End of WEEK 2, 4, 8 and 12.

40
Q

What is the maintenance phase of dosage for Balatacept?

A

IV end of WEEK 16 and every 4 WEEKS afterwards.

41
Q

What virus is there a risk of post transplant lymphoproliferative disease?

A

Epstein Barr Virus

42
Q

When is Balatacept used?

A

Alternative to Calcineurin inhibitors

43
Q

What are examples of mTOR inhibitors?

A

Sirolimus ‘Rapamycin’

44
Q

When is mTOR Inhibitors - Sirolimus used?

A

Alternative to Calcineurin Inhibitors and Anti-proliferative or used in combination with calcineurin inhibitors

45
Q

What is mTOR?

A

A serine/threonine protein kinase involved in the regulation of cell growth, proliferation and of protein synthesis and ribosome biogenesis.

46
Q

What drug is less nephrotoxic that Calcineurin inhibitors?

A

Sirolimus

47
Q

What drug is less likely to cause diabetes than Calcineurin inhibitors?

A

Sirolimus

48
Q

What drug can increase the risk of Pneumonitis but resolves after stopping treatment?

A

Sirolimus

49
Q

What drug can impair wound healing and is not used immediately after transplant?

A

Sirolimus

50
Q

What is the trough level on Sirolimus?

A

12-20ng/ml

51
Q

What is Basiliximab?

A

Chimeric (human/murine) monoclonal antibody against the IL-2 receptors (CD25 T cells must be activated for this to be expressed!)

52
Q

When is Basiliximab given?

A

Induction and 3-4 days post op!

53
Q

What is Alemtuxumab?

A

Humanised, rat IgG monoclonal antibody directed against CD52 cell surface antigen causing cell lysis and prolonged depression, also inhibits most monocytes, macrophages and natural killer cells.

54
Q

When is Alemtuxumab given?

A

Used to treat episodes of rejection

55
Q

What is Antithyrmocyte globulin (ATG)

A

S immunised with human thymocytes.

56
Q

How does Antithyromocyte globulin work?

A

Blocks large number of T cell membrane proteins (CD2, CD3, CD45) causing altered function, lysis and prolonged T cell depletion.

57
Q

What can cell lysis be responsible for?

A

Cytokine release syndrome - fever, chills, hypotension! this can last several hours!

58
Q

Before giving Antithymocyte globulin, what pre-medication is required?

A

Paracetamol, Chlorphenamine, and a Corticosteroid!

59
Q

When is Antithymocyte Globulin given?

A

Used to treat episodes of rejection!

60
Q

What drugs are given to a patient post renal transplant?

A
  • Prednisolone 20mg OD
  • Advagraf (Prolonged release tacrolimus) - 0.15mg/kg OF
  • Mycophenolate mofetil (after basiliximab) 750mg BD
  • Omeprazole 20mg OD
  • LMWH
  • Valganciclovir for 3-6 months; pt at risk of cytomegalovirus, xero + pt or donor.
  • Nystatin for 4 weeks post transplant
  • Co-trimoxole for 6 months prophylaxis to Pneumocystis Jiroveci (PCP)
    IF at risk of TB or latent TB carrier give prophylactix isonizide and pyridoxine.
61
Q

What drugs are given post Intestinal transplant?

A

○ Alemtuzumab SC - with prior pre-medication
○ Methylprednisolone IV then oral switch - plan to reduce or stop
○ Prograf (immediate release tacrolimus
○ Then starting Azathioprine or Mycophenolate
*Have 3 immunosuppressive agents post transplant

62
Q

Why do we use combined drug therapy in solid organ transplants?

A

Different MOA’s reduce steroid use and dose of monotherapy = better patient outcomes.

AI Exam 2 (16 decks)

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