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Therapeutics IV > Solid Organ Transplant - Block 4 > Flashcards

Solid Organ Transplant - Block 4 Flashcards

1
Q

What is the database used for transplant info such as waiting list organ donation, matching?

A

Organ procedurement and transplantation network (OPTN)

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2
Q

What are the clinical stages of rejection?

A

Hyperacute: minutes-hrs of transplant
* Massive immune response -> thrombosis preventing graft vascularization

Acute cellular reaction: first 6 months but diminished with immunosuppransants

Chronic: month-yrs
* Fibrosis

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3
Q

MOA of T cells?

A

Helper: attracts T-cytotoxic cells (CD4)
Cytotoxic: secretes cytokines that kills foreign body, cell diff (CD8)
Suppressor: shuts off the process

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4
Q

MOA of B cells?

A
  1. T cells excretions attract and activate B-cells
  2. Activated B-cells produces antibodies (memory)
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5
Q

MOA of neutrophils/eosinophils?

A

Recongize compliments and antibody receptors
* Engulfs and destroys

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6
Q

MOA of basophils and mast cells?

A

Secrete inflammatory mediators

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7
Q

Functins of macrophages and monocytoes?

A

Attracts lymphocytes

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8
Q

Tx types for transplants?

A
  1. Induction
  2. Maintenance
  3. Acute rejection
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9
Q

What is induction tx?

A

Provides high levels on immunosuppression at time of transplantation

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10
Q

Antibody agents for induction therapy?

A

Polyclonal antibody (antithymocyte globulins):
* ATGAM
* RATG

Monoclonal antibody: Alemtuzumab

IL2RA Interleukin 2 receptor antagonists: Basiliximab

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11
Q

MOA of Antithymocyte Globulins?

A
  1. Action against lymphocytes T-cells and B-cells
  2. Cells undergoing apoptosis release cytokines—Need to Premedicate
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12
Q

Premedication regimen for Antithymocyte Globulins?

A

Prior to each infusion: steroids, APAP, Benadryl

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13
Q

ADR of Antithymocyte Globulin?

A
  1. Anemia
  2. Leukopenia
  3. Thrombocytopenia
  4. Risk of infection
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14
Q

MOA of alemtuzumab?

A
  1. Monoclonal antibody against CD52 receptor
  2. CD52 expressed on T and B-cells
  3. Once alemtuzumab binds, causes cell death
  • Requiring premed with steroids, APAP, and Benadryl
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15
Q

Benefits of using Basiliximab?

A

DOES NOT cause infusion reactions

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16
Q

What are the steroids used for induction?

A

High dose methylprednisolone
* Patient will taper down on steroid use over course of hospital and discharge on prednisone

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17
Q

What is the goal of maintenance tx?

A

Prevent acute and chronic rejection while minimizing tox

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18
Q

What are maintenacne agents?

A

Calcineurin inhibitors:
* Cyclosporine A (CsA, Sandimmune, Neoral)
* Tacrolimus (FK-506, Prograf)

mTOR: sirolimus, everolimus

Corticosteroids: prednisone, prednisolone, methylprednisolon

Antimetabolite: Azathioprine, mycophenolate mofetl (MMF, Cellcept, Myfortic)

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19
Q

What is the backbone of immunosuppression

A

Calcinerin inhibitors

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20
Q

MOA of cyclosporine?

A

Reversible inhibition of T-cell

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21
Q

Indication for cyclosporine?

A

For maintenance therapy not for acute refection:
* Little effect on activated mature cytotoxic T cells so not for acute rjection

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22
Q

What are the PK properties of Sandimmue?

A
  1. Variable F
  2. Bile is needed for absorption
  3. Food delays absorption
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23
Q

What are the PK properties of Neoral?

A
  1. Consistant F
  2. Bile and food don’t affect absorption
  3. C max is higher
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24
Q

Are Sandimmune and Neoral interchangeable?

A

No

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25
Q

Metabolism of cyclosporine?

A

CYP3A4 and P-gp substrates

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26
Q

ADR of cyclosorine?

A
  1. Nephrotoxic
  2. Neurotoxic (HA, Sz, PN)
  3. HTN, HLD
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27
Q

Patient counseling for cyclosporine?

A
  1. Mix solution in beverage of choice (Tastes bad, use glass cup to mix, opened bottle is good for 2 months)
  2. Take cyclosporine at the same timedaily
  3. Avoid exposure to hot or cold temperature
  4. Refill 1 wk bfore our, compliance
  5. If traveling, take an extra bottle
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28
Q

Monitorng cyclosporine?

A

Therapeutic range: 100-400 ng/mL
1. Higher at first right after transplant
2. Lower goal as time post-transplant increases
3. Monitor daily levels immediatey after transplant and while tryng to titrate dose

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29
Q

MOA of tacrolimus?

A

Binds to FKBP (more potent than CsA)

30
Q

PK properties of tacrolimus?

A

Absorption: doesn’t require bile for absorption
Metabolism: CYP3A4 substrate, multiple DDI

31
Q

Dosing of tacrolimus?

A
  • Usually start around 0.1 mg/kg/day
  • Use Ideal or adjusted body weight for dosing
32
Q

ADR of tacrolimus?

A
  1. Alopecia
  2. Nephrotoxicity
  3. Neurotoxicity
  4. Hyperglycemia, HTN, HLD
  5. Electrolyte imbalances
33
Q

Monitorng of tacrolimus?

A

Trough: 5-20 ng/mL
* Use higher conc. at first then lower later
* Draw daily or 3x weekly during drug initiation and stabilization phase

34
Q

What is the difference between the presentations of acute rejection vs CSA (TAC nephrotoxicty)?

A

Acute rejection: fever, HTN, weight gain, graft sweliing, decreased urine volume

CSA/TAC nephrotoxicity: Afebrile, HTN, graft nontender, good urine output

35
Q

Drugs that increase calcineurin inhibitors levels?

A
  1. Azole antifungal
  2. Diltiazem, verapamil
  3. Macrolides
  4. PI
  5. Amiodarone
  6. Warfarin
  7. Grapefruit juice
36
Q

Drugs that decrease calcineurin inhibitors levels?

A
  1. Penytoin
  2. Phenobarbital
  3. Carbamazepine
  4. Rifampin
  5. St. Johns wart
37
Q

MOA of sirolimus?

A

Binds to FK binding protein, that complex binds to mTOR
* Inhibits T-cell proliferation
* Prvent B-cell differentition into antibody producing cells

38
Q

Indication for sirolimus?

A

Renal transplant

39
Q

Monitoring of sirolimus?

A

Target trough: 8-12 ng/mL

If used concurrently with Cyclosporine, may target lower trough level 4-12 ng/mL

40
Q

ADR of sirolimus?

A
  1. Leukopenia
  2. hrombocytopenia
  3. Hyperlipidemia
41
Q

DDI of sirolimus?

A

Substrate & Inhibitor of P-glycoprotein, substrate of CYP3A4
* Voriconazole and ketoconazole are CI and increase sirolimus concentration

42
Q

Indication of everolimus?

A

For kidney (low-mod immunologic risk only) or liver transplant

43
Q

Kidney dosing of everolimus?

A

Kidney: Basiliximab induction and CsA (reduced dose) maintenance
Liver: started 30 days after transplant with FK and corticosteroids

No LD
Trough goal: 3-8 ng/mL

44
Q

MOA of CS?

A

Inhibits of cytokines, IL-1, 2, 3, 6, TNF-a

45
Q

Induction tx of CS?

A

IV Methylprednisolone, 3 mg/kg

46
Q

Maintenance tx of CS?

A

Initial IV methylprednisolone post op Day 1: 0.5-2mg/kg then transition to PO Prednisone

Taper over next few months to 5-20mg/day

47
Q

ADR of CS?

A
  • CNS - euphoria, depression, psychosis
  • Hypertension - sodium and water retention
  • Infection and impaired wound healing
  • Increased appetite and weight gain
  • Osteoporosis
  • Cataracts
  • Glucose intolerance
  • Hyperlipidemia
  • Cushing’s Syndrome
48
Q

Types of MMF formulation?

A

Mycophenolate mofetil (MMF): Cellcept prodrug

MPA (Myfortic): Active drug

49
Q

MOA of MMF?

A
  1. Selective, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH)
  2. IMPDH is enzyme needed for purine synthesis and is inhibited T-cells and B-cells than aza
50
Q

How is MMF metabolized?

A

Hepatically

51
Q

Dosing MMF?

A

250mg Cellcept = 180mg Myfortic

Use Myfortic for those who can’t tolerate MMF

52
Q

ADR of MMF?

A

GI: diarrhea, vomiting, ab pain (change formulation)
PML: infection in brain
Neutropenia, anemia, thrombocytopenia

53
Q

BBW of azathioprine?

A

Increase risk of malignancy in humana

54
Q

MOA of belatacept?

A

Binds costimulatory ligands (CD80 and CD86) on APC preventing interaction with CD28 on T cells

55
Q

Indication and dosing of belatacept?

A

Indication: kidney transplant only
Dosing: Administered with Basiliximab + MMF + Corticosteroids
* Advantages: No CIs

56
Q

ADR of belatacept?

A
  1. Anemia
  2. UTI
  3. Peripheral edema
  4. Constipation
  5. N/V
  6. Hyperkalemia
  7. Hyperpyrexia
57
Q

Toxcity of cyclosporin and tacrolimus?

A

Nephrotoxcity

58
Q

Toxicity of sirolimus/everolimus?

A

Myelosuppression

59
Q

Toxicity of MMF, MPA?

A

Myelosuppression, N/V/D

60
Q

Toxicity of AZA?

A

Myelosuppression
N/V

61
Q

Toxcity of belatacept?

62
Q

Tx for acute rejection therapy?

A

IV steroids: Methylprednisolone
RATG (thyrmoglobulin): Antithymocyte globulin
Basiliximab: IL2-RA
Alemtuzumab: Anti-CD52

63
Q

Tx options for acute rejection therapy?

A
  1. Increasing the doses of current immunosuppressive drugs
  2. Starting “pulse” corticosteroids with subsequent dosage taper
  3. Addition of another immunosuppressant indefinitely
  4. Short-term treatment with a polyclonal or monoclonal antibody
64
Q

Ex of CS regimen

A
  • Methylprednisolone
  • High dose 1000mg IV Daily x 3-5 days
  • Taper back to maintenance dose of Prednisone PO
65
Q

Infections associated with acute rejection episodes? Tx?

A
  1. CMV (Cytomegalovirus): Valganiclovir
  2. BK virus: in kidney transplants if detected, reduce immunosuppression treat with Cidofovir
  3. PCP: Bactrim for 6-12 months post-transplant
  4. HepC: Antivirals
  5. No live vaccinations
  6. Fungal prophylaxis: Voriconazole, itraconazole
66
Q

INdcations for fungal prophylaxis?

A
  1. LArge blood transfusion
  2. Prolonged ICU stay
  3. Prior blood spectrum ABX use
  4. Known fungal colonization
  • Lung or heart/lung transplant
67
Q

Tx of HTN complication

A

Due to CIs, CS, Impaired kidney-graft function

1st line: CCB (Amlodipine)

68
Q

Tx for HLD complication?

A

Due to CI, CS, and sirolimus

1st line: statin effective but can cause rhabdomyolysis when combined with CI and potential hepatotoxicty in liver transplant patients

69
Q

What increases the diabetes complications?

A
  1. AA and hispanic
  2. > 40 YO
  3. Pretransplant diabetes status
  4. Family hx
  5. Obesity
  6. Up to 40% will require insulin therapy
70
Q

Overal induction regimen?

A

Interleukin 2 receptor antagonists (IL2RA):
* Basiliximab 20mg IV x 1 (repeat again on Day 3 or 4)

Alemtuzumab (Campath) 30mg SUBQ x 1
ATG or RATG
* Thymoglobulin (RATG) most common
* Protocols range from 1.5 mg/kg IV daily x 5 doses or 6mg/kg x 1 dose

Prednisone equivalent
* Methylprednisolone 3mg/kg IV or can be up to 1000mg x 1 prior to surgery

71
Q

Overall maintenance tx?

A

CsA, Tacrolimus, Sirolimus, MMF, Corticosteroids

71
Q

Overall rejection tx

A

Glucocorticoid (first line, high dose): IV methylprednisolone

ATG or RATG

Therapeutics IV (39 decks)

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