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Renal Exam > Transplant Pharmacology > Flashcards

Transplant Pharmacology Flashcards

1
Q

induction therapy in transplants

A

*a short-term course of immunosuppressive drugs given before/during/immediately after a transplant to reduce the risk of rejection

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2
Q

maintenance therapy in transplants

A

*immunosuppressive treatment given after a transplant to prevent acute rejection/loss of transplanted organ

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3
Q

induction therapy agents - classes/examples

A
  1. non-lymphocyte depleting: well-tolerated
    a. IL-2 receptor antagonists = basiliximab
  2. lymphocyte depleting: MORE POTENT
    a. polyclonal antibody preparation = rabbit anti-thymocyte globulin or r-ATG (thymoglobulin)
    b. monoclonal antibody preparation = alemtuzumab
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4
Q

maintenance therapy agents - classes/examples

A
  1. calcineurin inhibitors (CNIs):
    -tacrolimus
    -cyclosporine
  2. mTOR inhibitors:
    -sirolimus
    -everolimus
  3. anti-proliferative/antimetabolite agents:
    -mycophenolic acid or mycophenolate mofetil
    -azathioprine
  4. corticosteroids = prednisone
  5. belatacept (blocks T cell co-stimulation signal)
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5
Q

corticosteroids - MOA (general)

A

*widespread anti-inflammatory effects
*ex: prednisone

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6
Q

azathioprine - drug class, MOA (general)

A

*prevents lymphocyte proliferation
*class: anti-proliferative / antimetabolite agent
*used to prevent rejection (maintenance therapy) in renal transplantions

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7
Q

mycophenolic acid / mycophenolate mofetil - drug class, MOA (general)

A

*prevents lymphocyte proliferation
*class: anti-proliferative / antimetabolite agent
*used to prevent rejection (maintenance therapy) in renal transplantions

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8
Q

calcineurin inhibitors - MOA, examples (general)

A

*block IL-2 gene transcription
*ex: tacrolimus, cyclosporine
*used to prevent rejection (maintenance therapy) in renal transplantions

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9
Q

mTOR inhibitors - MOA, examples (general)

A

*blocks IL-2 receptor signal transduction
*ex: sirolimus, everolimus
*used to prevent rejection (maintenance therapy) in renal transplantions

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10
Q

alemtuzumab - drug class, MOA (general)

A

*anti-CD52 monoclonal antibody
*MOA: depletion of lymphocytes
*used to prevent rejection (induction therapy) in renal transplantions

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11
Q

maintenance therapy regimen

A

*agent 1: CALCINEURIN INHIBITORS, mTOR inhibitors, or belatacept
*agent 2: mycophenolic acid, azathioprine, or mTOR inhibitor
*agent 3: prednisone

most common: calcineurin inhibitor + azathioprine or mycophenolic acid + prednisone

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12
Q

cyclosporine - drug class, MOA, ADEs

A

*calcineurin inhibitor
*block IL-2 gene transcription (by binding to cyclosporine-binding protein)
*ADEs: nephrotoxicity, HTN, dyslipidemia, hyperglycemia, headache/tremors, gingival hyperplasia, HIRSUTISM

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13
Q

tacrolimus - drug class, MOA, ADEs

A

*calcineurin inhibitor
*block IL-2 gene transcription (by binding to FK506 protein)
*ADEs: nephrotoxicity, HTN, dyslipidemia, hyperglycemia, headache/tremors, ALOPECIA

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14
Q

drug interactions with calcineurin inhibitors - enzyme inducers

A

*metabolism via Cytochrome P450 3A4
*enzyme inducers → lower levels of calcineurin inhibitors
1. rifampin
2. phenytoin
3. St John’s-wort

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15
Q

drug interactions with calcineurin inhibitors - enzyme inhibitors

A

*metabolism of CNIs via Cytochrome P450 3A4
*enzyme inhibitors → raise levels of calcineurin inhibitors
1. NDHP CCBs - diltiazem, verapamil
2. antifungals - fluconazole, ketoconazole
3. antibiotics - erythromycin, clarithromycin, HAART

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16
Q

mycophenolate mofetil / mycophenolic acid - MOA

A

*inhibits de novo purine synthesis via IMP dehydrogenase
*blocks proliferation of T cells and B cells
*used to prevent rejection (maintenance therapy) in renal transplantions

note - do NOT take with magnesium or calcium

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17
Q

mycophenolate mofetil / mycophenolic acid - ADEs

A

*diarrhea
*leukopenia, anemia
*teratogenic
*increases risk of skin cancer

note - do NOT take with magnesium or calcium

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18
Q

azathioprine - MOA

A

*imidazole derivative of 6-mercaptopurine
*gets incorporated into DNA and inhibits synthesis of RNA in T and B cells
*used to prevent rejection (maintenance therapy) in renal transplantions

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19
Q

azathioprine - ADEs

A

*bone marrow suppression (esp leukopenia)
*pancreatitis
*INTERACTION WITH ALLOPURINOL

20
Q

sirolimus - place in therapy

A

*second-line agent
*potentially less nephrotoxic than the CNIs

21
Q

sirolimus - MOA

A

*binds mTOR (a key regulatory kinase in cell division; blocks the G1-S phase transition)
*antiproliferative and anti-neoplastic

*note - in cases of recurrent skin cancer, reduce dose of antimetabolite first (mycophenolate or azothioprine)

22
Q

sirolimus - ADEs

A

*anemia, leukopenia, thrombocytopenia
*DELAYED WOUND HEALING
*LYMPHOCELE FORMATION
*increased cholesterol & triglyceride levels
*proteinuria
*edema
*pneumonitis

23
Q

corticosteroids (prednisone) - MOA

A

*prevent transcription of cytokine genes and cytokine receptors
*reduces T-cell activation

24
Q

corticosteroids (prednisone) - ADEs

A

*GI ulcerations
*hyperglycemia
*osteoporosis
*acne
*CNS effects
*HTN
*increased appetite
*hyperlipidemia
*other

25
Q

infections after transplantation: 1st month post-transplant

A

*similar infections to non-immunosuppressed surgical patients:
-wound infections
-urinary tract infections
-line-related infections

26
Q

infections after transplantation: months 1-6 post-transplant

A

*cytomegalovirus (CMV)
*polyoma virus (BK)
*urinary tract infections

27
Q

infections after transplantation: > 6 months post-transplant

A

*urinary tract infections, community-acquired pneumonia
*BK virus, CMV
*OPPORTUNISTIC INFECTIONS & REACTIVATION: Listeria monocytogenes, Nocardia, TB, etc

28
Q

CMV infection - presentation

A

*acute viral syndrome with leukopenia
*tissue invasive disease: hepatitis, pneumonitis (cough, dyspnea), pancreatitis, colitis (diarrhea)

29
Q

CMV infection - risk factors

A

*CMV seronegative (no prior immunity)
*HIGHEST RISK: donor seropositive, recipient seronegative
*recent treatment with lymphocyte-depleting agent (induction phase therapy for transplant)

30
Q

CMV infection - diagnosis

A

*demonstration of CMV viremia by PCR

31
Q

CMV infection - prophylaxis & treatment

A

*prophylaxis: valganciclovir, letermovir

*tx: IV ganciclovir or oral valganciclovir (MOA - inhibits viral DNA synthesis)

*resistant CMV infection: foscarnet or MARIBAVIR

32
Q

polyoma virus (BK virus) - presentation

A

*typically ASYMPTOMATIC
*can cause renal failure, hemorrhagic cystitis

33
Q

polyoma virus (BK virus) - risk factors

A

*older age
*recent treatment for rejection

34
Q

polyoma virus (BK virus) - diagnosis

A

*demonstration of BKV viremia by PCR
*demonstration of BK nephropathy (mimics cellular rejection but SV40 stain positive and has inclusion bodies) by allograft biopsy

35
Q

polyoma virus (BK virus) - treatment

A

*reduction of immunosuppression
*IVIG, cidofovir?

36
Q

infection prophylaxis in transplant patients - antifungals

A

*prevent oral and esophageal candidiasis
*fluconazole, clotrimazole

*main ADEs = LIVER DYSFUNCTION, HIGH TACROLIMUS LEVEL

37
Q

infection prophylaxis in transplant patients - vangalciclovir

A

*prevents CMV infection
*high risk (+/-_ vs. low risk donor/recipient serologies = 6 months
*letermovir is an alternative / second-line agent

*main ADE = LEUKOPENIA

38
Q

infection prophylaxis in transplant patients - trimethoprim-sulfamethoxazole (TMP-SMX or Bactrim)

A

*prevents against:
-pneumocytsitis jirovecii
-Nocardia/toxoplasma
-UTIs
*alternatives: pentamidine, dapsone, atovaquone

*main ADE = HYPERKALEMIA

39
Q

common malignancies after transplantation

A

*immunosuppressive medications increase risk of certain malignancies

  1. non-melanoma skin cancers (BCC, SCC) - account for > 50% of all malignancies in transplant recipients
  2. post-transplant lymphoproliferative disorder (PTLD) - usually arises after primary infection or reactivation of latent EBV infection
40
Q

causes of early graft dysfunction

A

*vascular issues
*extrinsic compression
*acute tubular necrosis
*acute pyelonephritis
*DRUG TOXICITY - CALCINEURIN INHIBITOR RELATED
*acute rejection
*urinary obstruction/leaks

41
Q

causes of later (>3 months) graft dysfunction

A
  1. intrinsic renal process:
    -chronic rejection, chronic drug toxicity, late acute rejection, BK virus, transplant pyelonephritis, etc
  2. mechanical: ureteral obstruction or stricture
42
Q

features of acute calcineurin inhibitor (CNI) toxicity

A

*reduced renal blood flow (vasoconstriction)
*tubular toxicity (vacuolization)
*association with genes controlling intracellular concentration of CNI in kidney

43
Q

features of chronic calcineurin inhibitor (CNI) toxicity

A

*stripe-like interstitial fibrosis
*secondary FSGS glomerular lesions
*renal failure after non-renal solid organ transplant

44
Q

T-cell mediated rejection (TCMR) - Banff Criteria

A

*borderline tubulitis
*1A/B: tubulitis 5-10 or > 10 inflammatory cells per tubule
*2A/B: endothelitis/endovasculitis
*3: transmural infarction

45
Q

T-cell mediated rejection (TCMR) - treatment

A

*steroids
*rabbit antithymocyte globulin (ATG) for stages 1B and above

46
Q

antibody-mediated rejection (AMR) - diagnostic criteria

A

*histology: peritubular capillaritis
*detection of C4d deposition on biopsy
*positive DSA (donor specific antibodies) titers

47
Q

antibody-mediated rejection (AMR) - treatment

A

*plasmapheresis/IVIG
*rituximab (anti-CD20): targets B lymphocytes
*anti C5 antibody (eculizimab)

Renal Exam (44 decks)

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