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850 > Solid Organ Transplant > Flashcards

Solid Organ Transplant Flashcards

1
Q

Indications for Transplant

A
  • Kidney: diabetes, HTN, lupud, PCKD
  • Liver: alcoholic cirrhosis, NASH, HBV/HCV, HCC, APAP toxicity
  • Pancreas: Diabetes, congenital abnormalities
  • Heart: Ischemic heart disease, congenital abnormalities, idiopathic cardiomyopathy, valvular disease
  • Lung: CF, pulmonary HTN. pulmonary fibrosis, COPD, emphysema
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2
Q

Goals of Immunosuppression

A
  • Prevent rejection
  • Avoid complications with high dose immunosuppressants
  • Patient and grant survival
  • Patient adherence
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3
Q

Induction Therapy Goals

A
  • Prevent early acute allograft rejection using intense, prophylactic immunosuppression therapy
  • Produces profound deficiency on T and/or B cells that can last months
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4
Q

Induction Therapy Options

A
  • Basiliximab
  • Antithymocyte globulin
  • Alemtuzumab
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5
Q

Basiliximab

A
  • Simulect
  • MoA: Blocks T-proliferation via interleukin-2 reception antaognism (anti-CD25 antibodies)
  • Used in lowest immunologic risk patients
  • Decreased infection rates when compared to other agents
  • Does not lead to sustained depletion of lymphocytes and related CD4 helper T-cells
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6
Q

Antithymocyte Globulin

A
  • Thymoglobulin
  • MoA: Binds to T-cell surfaces antigens leading to the elimination of T-cells
  • Used in moderate to high immunologic risk
  • Increased risk for CMV and BKV
  • PJP and other invasive fungal pathogens have been associated with thymoglobulin
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7
Q

Alemtuzumab

A

-Campath
-MoA: binds to CD52 on T-cells,
B-cells, NK cells, and monocytes/macrophages and causes complement activation and antibody-dependent cellular toxicity
-“AIDS” in a bottle, results to pan T-cell depletion
-Used as steroid sparing induction
-CD4/CD8 counts nadir at 4 weeks, 1+ years for recovery
-Associated with many opportunistic infections

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8
Q

Maintenance Therapy Goals

A
  • Prevent allograft rejection
  • Maintain an adequate balance of graft fxn, AE, and prevention of infection
  • Lifelong immunosuppression
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9
Q

Maintenance Therapy Options

A
  • Corticosteroids
  • Calcineurin inhibitors
  • Antimetabolites
  • mTOR inhibitors
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10
Q

Corticosteroids

A
  • Oldest immunosuppresive agent used in transplant
  • MoA: inhibition of cytokine gene expression, modification of lymphocyte distribution and fxn, anti-inflammatory effects
  • Dosing: Prednisone 5-10 mg/day (maintenance dose), higher doses are used for induction and rejection therapy
  • TONS of SE (short and long term)
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11
Q

Tacrolimus

A
  • Calcineurin Inhibitors
  • Capsules (ER and IR), IV, or oral suspension
  • Also called FK506
  • MoA: Inhibits T-cell activity through inhibition of IL-2 production
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12
Q

Tacrolimus ADME

A
  • Absorption: incomplete and variable, best absorbed on an empty stomach
  • Highly lipophilic (99% protein bound)
  • Metabolism: extensive CYP3A4, p-gp (IR 1/2 life ~9 hours, ER 1/2 life ~34 hours)
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13
Q

Tacrolimus Dosing

A
  • IR: 0.05-0.1 mg/kg/day in divided doses
  • ER: 0.1-0.2 mg/kg/day one time daily
  • Dose adjust based on [trough] and renal fxn
  • [Goal] varies: time after transplant, type of organ transplanted, infection
  • Therapeutic range: 5-15 ng/mL
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14
Q

Tacrolimus Interactions

A
  • Primarily through hepatic metabolism CYP3A4, inhibition or induction
  • P-gp substrate
  • Antacids: physical interaction => reduced absorption, separate by at least 2 hours
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15
Q

Cyclosporine

A
  • Calcineurin Inhibitor
  • Modified microemulsion formulation, unmodified formulation as well
  • MoA: Inhibits T-cell proliferation through inhibition of IL-2 production
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16
Q

Cyclosporine ADME

A
  • Absorption: erratic and incomplete, non-modified is largely dependent on food/bile/GI motility while modified is not
  • Distribution: highly lipophilic (98% protein bound)
  • Metabolism: CYP3A4 (extensive), p-gp
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17
Q

Cyclosporine Dosing

A
  • 10-15 mg/kg/day in divided doses to attain target trough levels
  • Dose adjusted based on [trough] and renal fxn ([goal] varies based on time after transplant, organ transplanted, infection)
  • Therapeutic Range: 50-200 ng/mL
18
Q

Cyclosporine Interactions

A
  • Primarily through hepatic metabolism, CYP3A4 induction or inhibition
  • P-gp substrate
  • Anticipate and manage: high inter/intra-patient variability
  • Nephrotoxic drugs should be used with caution
  • Consistent administration with or without food
19
Q

Mycophenolate

A
  • Antiproliferative
  • Products: MMF, mycophenolate sodium
  • Prodrugs for MPA
  • MoA: inhibition of ionsine monophosphate dehydrogenase IMPDH => inhibits de novo guanosine nucleotide synthesis
  • Prevents T and B lymphocytes proliferation
20
Q

Mycophenolate Dosing

A
  • 200-1000 mg PO BID (MMF)
  • 180-720 mg PO BID (Myfortic)
  • Dosing conversion 1000 mg cellcept = 720 mg myfortic
  • Myfortic is EC for DR, claims to reduce GI SE
21
Q

Mycophenolate SE

A
  • GI intolerance: N/V, diarrhea

- Leukopenia, anemia, thrombocytopenia

22
Q

Mycophenolate Drug Interactions

A
  • Aluminum/magnesium containing antacids (separate by at least 2 hours)
  • Cholestyramine
  • Divalent/trivalent cations (iron)
  • PPI
  • Oral contraceptives
23
Q

Mycophenolate + Pregnancy

A
  • Shown to cause fetal harm
  • Negative pregnancy test prior to starting medication
  • Women of child-bearing age required to use at least two methods of contraception
24
Q

Azathioprine

A
  • Antiproliferative
  • Prodrug of 6-MP
  • MoA: antagonist of purine metabolism, prevents T and B lymphocytes proliferation
  • Rare Uses: intolerance to mycophenolate, women that want to become pregnant
  • Dosing: 3-5 mg/kg/day initially, then decrease to 1-3 mg/kg/day
25
Q

Azathioprine AE

A
  • GI Intolerance
  • Leukopenia, anemia, thrombocytopenia
  • Increased alkaline phosphatase, total bilirubin, and transaminases
26
Q

Azathioprine Drug Interactions

A
  • 6-MP: profound myelosuppression

- Allopurinol: inhibits metabolism of azathioprine and 6-MP leading to profound myelosuppression

27
Q

Sirolimus

A
  • mTOR Inhibitor
  • MoA: Binding to FKTB-12 => inhibits MTOR, suppresses cytokine mediated T-cell proliferation
  • Use: May be used to replace mycophenolate or a calcineurin inhibitor
  • Dosing: 1-5 mg/day to attain target trough levels
28
Q

Sirolimus AE/Interactions

A

AE

  • Edema
  • Anemia
  • Impaired wound healing
  • Interstitial lung disease
  • Proteinuria
  • Hyperlipidemia

Interactions

  • Metabolized through CYP3A4
  • Similar interactions with cyclosporine and tacrolimus
29
Q

Everolimus

A
  • mTOR inhibitor
  • MoA: Binding to FKRP-12 => inhibits mTOR, suppresses cytokine mediated T-cell proliferation
  • Use: renal transplant rejection prophylaxis
  • Off-label use: heart transplant rejection prophylaxis
  • Dosing: 0.75-1 mg PO BID to attain target trough levels
30
Q

Everolimus

A

AE

  • Edema
  • Anemia
  • Impaired wound healing
  • Proteinuria
  • Hyperlipidemia

Interactions

  • Metabolized CYP3A4: similar drug interactions as cyclosporine and tacrolimus
  • Consistent administration in regards to food
31
Q

Belatacept

A
  • Indication: maintenance immunosuppression therapy in renal transplant recipients
  • MoA: Binds to CD80 and CD86 receptors on APCs and blocking CD-28 mediated costimulation of T-cells
32
Q

Belatacept Dosing

A

Initial

  • 10 mg/kg IV post-operative day 0 and 5
  • 10 mg/kg IV end of week 2, 4, 8, 12

Maintenance Phase

  • End of week 16
  • 5 mg/kg every 4 weeks
33
Q

Belatacept AE

A
  • Post-transplant lymphoproliferation disorder
  • GI disturbances
  • HTN
  • Peripheral edema
  • Anemia, leukopenia
  • NO long term renal toxicity

Black-Box Warning

  • Increased risk of infections
  • PTLD associated with EBV seronegative
34
Q

Generic Medications

A
  • Tacrolimus
  • Mycophenolate
  • Cyclosporine
  • Sirolimus
  • *Patients are encouraged to maintain consistency with the product they use**
35
Q

Immunosuppresion Considerations

A
  • Rejection
  • Toxicity
  • AE
  • Variability
  • Infection
  • Malignancy
  • Cost
  • DDI
36
Q

Immunosuppression Complications

A
  • CV
  • Infectious
  • Malignancy
37
Q

CV Complications

A
  • Leading cause of mortality in renal transplant recipients
  • HTN
  • Hyperlipidemia
  • Diabetes
38
Q

Infectious Complications

A
  • Highest risk immediately following transplant and rejection treatment: related to degree of immunosuppression
  • Opportunistic infections
  • Atypical organisms
  • Prophylaxis
39
Q

Malignancy

A
  • Related to degree of immunosuppression: increased risk with increased survival
  • Lung, breast, colon, and prostate cancer are not increased compared to general population
  • Increased risk of lymphomas and lymphoproliferative disorders, Kaposi’s sarcoma, renal carcinoma, and skin cancers
40
Q

Rejection

A
  • Cellular rejection: hyperacute rejection, acute rejection

- Antibody-mediated rejection (AMR): acute or chronic AMR

41
Q

Barriers to Adherence (SMURF)

A
  • System: PA, transportation
  • Motivation: depression, feeling “different”
  • Understanding: education level, language barriers
  • Recall: variable schedule, distractions
  • Financial: cost of medications
42
Q

Limitations in Transplant

A
  • Every center practices differently
  • Most evidence based on retrospective single-center experiences
  • Many medications are used “off-label”

850 (23 decks)

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