Organ transplant Flashcards
What are the main complications that reduce recipient’s life after kidney transplant?
CDV, malignancy and infection
What are the signs of infection?
fatigue, fever, aching joints, headache, watery blister on chest/back, lesions on tongue, difficulty swallowing, abnormal vaginal discharge, redness, swelling, dry cough, pneumonia
What are the 3 prophylactic anti-infective therapies?
PCP (trimethoprim/sulfamethoxazole), CMV (ganciclovir, valganciclovir), Oral thrust (nystatin liquid)
What are 3 examples of malignancy and what does it increase the incidence of?
skin lesion, lymphomas, cervical cancer
It increases the incidence of lung, prostate, breast, rectum or colon cancer
What are the signs of organ rejection in kidney?
Kidney: Reduced urine output, raised SeCR (decreased renal function)
What are the signs of organ rejection in liver?
Liver: jaundice, raised LFT, itching, easy bleeding, fever fatigue
What are the signs of organ rejection in heart?
Shortness of breath, reduced tolerance to exertion
Explain the rejection process
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
What does the immunosuppressant drug target?
the different stages in T-cell activation and immune response
What are the two examples of calcineurin inhibitors (CNI) and what do they target?
Tacrolimus and cyclosporine
They inhibit production of IL2 and other cytokines
Which of the CNI is more potent with lower acute rejection rate?
tacrolimus
What are the ADE of tacrolimus?
Hyperglycaemia, headache, GI problems, high K+ and Mg+
What are the ADE of cyclosporine?
Nephrotoxicity, hepatotoxicity, gum hyperplasia, hirutism
What are the CNIs interacted with?
CYP3A4 inducers and inhibitors
What are the two examples of anti-proliferatives and what do they target?
Azathioprine, mycophenolate
They inhibit DNA synthesis preventing activated T-cells from proliferating
Which of the anti-proliferatives is more potent with lower acute rejection rate?
Mycophenolate
What are the ADE of azathioprine?
Hepatotoxic and cholestasis
What should you avoid with azathioprine?
allupurinol
What is the ADE of mycophenolate?
diarrhoea, bone marrow suppression, anaemia, thrombocytopenia
What are the two examples of oral corticosteroids and what do they do?
Prednisolone, prednisone
They bind to receptor proteins in cytoplasm and reduce synthesis of cytokines, chemokines, adhesion molecules and other immune mediators
What is the counselling point of oral corticosteroids?
reduce dose slowly and take in the morning to reduce GI disturbance
What are the ADE of oral corticosteroids?
Weight gain, hyperlipidaemia, hypertension, hyperglycaemia, osteoporosis, impaired growth
Can you use the oral corticosteroids in pregnancy and bf?
Yes in pregnancy at low dose but avoid in BF
What should you avoid with oral corticosteroids?
Antiepileptic drugs and antibiotics decrease its effect
HIV protease inhibitor increases its level
NSAIDS and warfarin increase gastric ulceration and bleeding
What are the two examples of mTOR inhibitors and what do they do?
Sirolimus and everolimus
They block IL-2 mediated transduction pathways preventing movement of activated T-cell from G1 to S phase of proliferation
What are the ADE of mTOR inhibitors?
Hypertension, hyperlipidaemia, thrmbocytopenia, impaired healing
Does mTOR inhibitor cause nephrotoxicity?
NO
What can you use mTOR in combination with?
with CNI and also to replace CNI
What are the two examples of anti-interleukin-2 receptor antibodies and what do they do?
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
When are the anti-interleukin-2 receptor antibodies used?
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
What medications do we use for acute rejection?
high dose steroids first but if it doesn’t work, use anti-T-cell antibodies (IV) for a few days, then change CNI
What are the examples of anti-T-cell antibodies and what do they do?
ATG (Rabbit), ALG (horse), OKT3 (mouse)
They bind to T-cell receptors resulting in destruction of T-cells
What is bad about anti-T-cell antibodies?
they are not specific so it can knock out the immune system
What are the ADE of anti-T-cell antibodies?
increased infection, thrombocytopenia, severe reaction first due to cytokine release, pulmonary oedema, fever, rigors (give in combination with antihistamine, steroids)
What is the induction therapy combination?
AI2 receptor antibody + methylprednisolone + AT antibody
What is the LT maintenance combination?
CNI + AP + OC — mTOR (with or in replacement)
Which classes of immunosuppressants do not need TDM?
Oral corticosteroids, AI2-receptor antibodies, AT antiody
Which drugs need which type of monitoring?
cyclosporine: C0,C2 (pose dose conc)
tacrolimus, sirolimus, everolimus: C0 (just before dosing)
What is the intervention of TDM?
To maintain the levels within a pre-defined range in individual
Clinical pharmacists individualise the therapy based around drug and patient exposure
