Organ transplant

Question 1

What are the main complications that reduce recipient’s life after kidney transplant?

Answer 1

CDV, malignancy and infection

Question 2

What are the signs of infection?

Answer 2

fatigue, fever, aching joints, headache, watery blister on chest/back, lesions on tongue, difficulty swallowing, abnormal vaginal discharge, redness, swelling, dry cough, pneumonia

Question 3

What are the 3 prophylactic anti-infective therapies?

Answer 3

PCP (trimethoprim/sulfamethoxazole), CMV (ganciclovir, valganciclovir), Oral thrust (nystatin liquid)

Question 4

What are 3 examples of malignancy and what does it increase the incidence of?

Answer 4

skin lesion, lymphomas, cervical cancer

It increases the incidence of lung, prostate, breast, rectum or colon cancer

Question 5

What are the signs of organ rejection in kidney?

Answer 5

Kidney: Reduced urine output, raised SeCR (decreased renal function)

Question 6

What are the signs of organ rejection in liver?

Answer 6

Liver: jaundice, raised LFT, itching, easy bleeding, fever fatigue

Question 7

What are the signs of organ rejection in heart?

Answer 7

Shortness of breath, reduced tolerance to exertion

Question 8

Explain the rejection process

Answer 8

Resting T-cells identify donor antigen as foreign and become activated which secretes cytokines (IL2) that leads to inflammatory response
This leads to T-cells, B-cells activation and proliferation and recrutiment of macrophages
Graft tissue destruction, impaired ability of transplant to function

Question 9

What does the immunosuppressant drug target?

Answer 9

the different stages in T-cell activation and immune response

Question 10

What are the two examples of calcineurin inhibitors (CNI) and what do they target?

Answer 10

Tacrolimus and cyclosporine

They inhibit production of IL2 and other cytokines

Question 11

Which of the CNI is more potent with lower acute rejection rate?

Answer 11

tacrolimus

Question 12

What are the ADE of tacrolimus?

Answer 12

Hyperglycaemia, headache, GI problems, high K+ and Mg+

Question 13

What are the ADE of cyclosporine?

Answer 13

Nephrotoxicity, hepatotoxicity, gum hyperplasia, hirutism

Question 14

What are the CNIs interacted with?

Answer 14

CYP3A4 inducers and inhibitors

Question 15

What are the two examples of anti-proliferatives and what do they target?

Answer 15

Azathioprine, mycophenolate

They inhibit DNA synthesis preventing activated T-cells from proliferating

Question 16

Which of the anti-proliferatives is more potent with lower acute rejection rate?

Answer 16

Mycophenolate

Question 17

What are the ADE of azathioprine?

Answer 17

Hepatotoxic and cholestasis

Question 18

What should you avoid with azathioprine?

Answer 18

allupurinol

Question 19

What is the ADE of mycophenolate?

Answer 19

diarrhoea, bone marrow suppression, anaemia, thrombocytopenia

Question 20

What are the two examples of oral corticosteroids and what do they do?

Answer 20

Prednisolone, prednisone
They bind to receptor proteins in cytoplasm and reduce synthesis of cytokines, chemokines, adhesion molecules and other immune mediators

Question 21

What is the counselling point of oral corticosteroids?

Answer 21

reduce dose slowly and take in the morning to reduce GI disturbance

Question 22

What are the ADE of oral corticosteroids?

Answer 22

Weight gain, hyperlipidaemia, hypertension, hyperglycaemia, osteoporosis, impaired growth

Question 23

Can you use the oral corticosteroids in pregnancy and bf?

Answer 23

Yes in pregnancy at low dose but avoid in BF

Question 24

What should you avoid with oral corticosteroids?

Answer 24

Antiepileptic drugs and antibiotics decrease its effect
HIV protease inhibitor increases its level
NSAIDS and warfarin increase gastric ulceration and bleeding

Question 25

What are the two examples of mTOR inhibitors and what do they do?

Answer 25

Sirolimus and everolimus They block IL-2 mediated transduction pathways preventing movement of activated T-cell from G1 to S phase of proliferation

Question 26

What are the ADE of mTOR inhibitors?

Answer 26

Hypertension, hyperlipidaemia, thrmbocytopenia, impaired healing

Question 27

Does mTOR inhibitor cause nephrotoxicity?

Answer 27

NO

Question 28

What can you use mTOR in combination with?

Answer 28

with CNI and also to replace CNI

Question 29

What are the two examples of anti-interleukin-2 receptor antibodies and what do they do?

Answer 29

Basiliximab, daclizumab They act as antagonists at IL-2 receptor on T-cells, blocking binding of IL-2 preventing T-cells from becoming activated and proliferate

Question 30

When are the anti-interleukin-2 receptor antibodies used?

Answer 30

for ST induction therapy (for the first few weeks after transplant when rejection is high), it can reduce the severity of early acute rejection without causing ADE

Question 31

What medications do we use for acute rejection?

Answer 31

high dose steroids first but if it doesn't work, use anti-T-cell antibodies (IV) for a few days, then change CNI

Question 32

What are the examples of anti-T-cell antibodies and what do they do?

Answer 32

ATG (Rabbit), ALG (horse), OKT3 (mouse) | They bind to T-cell receptors resulting in destruction of T-cells

Question 33

What is bad about anti-T-cell antibodies?

Answer 33

they are not specific so it can knock out the immune system

Question 34

What are the ADE of anti-T-cell antibodies?

Answer 34

increased infection, thrombocytopenia, severe reaction first due to cytokine release, pulmonary oedema, fever, rigors (give in combination with antihistamine, steroids)

Question 35

What is the induction therapy combination?

Answer 35

AI2 receptor antibody + methylprednisolone + AT antibody

Question 36

What is the LT maintenance combination?

Answer 36

CNI + AP + OC --- mTOR (with or in replacement)

Question 37

Which classes of immunosuppressants do not need TDM?

Answer 37

Oral corticosteroids, AI2-receptor antibodies, AT antiody

Question 38

Which drugs need which type of monitoring?

Answer 38

cyclosporine: C0,C2 (pose dose conc) | tacrolimus, sirolimus, everolimus: C0 (just before dosing)

Question 39

What is the intervention of TDM?

Answer 39

To maintain the levels within a pre-defined range in individual Clinical pharmacists individualise the therapy based around drug and patient exposure