Therapeutics IV > Solid Organ Transplant - Block 4 > Flashcards

Solid Organ Transplant - Block 4 Flashcards

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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
Metabolism of cyclosporine?
CYP3A4 and P-gp substrates
26
ADR of cyclosorine?
1. Nephrotoxic 2. Neurotoxic (HA, Sz, PN) 3. HTN, HLD
27
Patient counseling for cyclosporine?
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
28
Monitorng cyclosporine?
**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
29
MOA of tacrolimus?
Binds to FKBP (more potent than CsA)
30
PK properties of tacrolimus?
**Absorption:** doesn't require bile for absorption **Metabolism:** CYP3A4 substrate, multiple DDI
31
Dosing of tacrolimus?
* Usually start around 0.1 mg/kg/day * Use Ideal or adjusted body weight for dosing
32
ADR of tacrolimus?
1. Alopecia 2. Nephrotoxicity 3. Neurotoxicity 4. Hyperglycemia, HTN, HLD 5. Electrolyte imbalances
33
Monitorng of tacrolimus?
**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
What is the difference between the presentations of acute rejection vs CSA (TAC nephrotoxicty)?
**Acute rejection:** fever, HTN, weight gain, graft sweliing, decreased urine volume **CSA/TAC nephrotoxicity:** Afebrile, HTN, graft nontender, good urine output
35
Drugs that increase calcineurin inhibitors levels?
1. Azole antifungal 2. Diltiazem, verapamil 3. Macrolides 4. PI 5. Amiodarone 6. Warfarin 7. Grapefruit juice
36
Drugs that decrease calcineurin inhibitors levels?
1. Penytoin 2. Phenobarbital 3. Carbamazepine 4. Rifampin 5. St. Johns wart
37
MOA of sirolimus?
Binds to FK binding protein, that complex binds to mTOR * Inhibits T-cell proliferation * Prvent B-cell differentition into antibody producing cells
38
Indication for sirolimus?
Renal transplant
39
Monitoring of sirolimus?
**Target trough:** 8-12 ng/mL If used concurrently with Cyclosporine, may target lower **trough level 4-12 ng/mL**
40
ADR of sirolimus?
1. Leukopenia 2. hrombocytopenia 3. Hyperlipidemia
41
DDI of sirolimus?
Substrate & Inhibitor of P-glycoprotein, substrate of CYP3A4 * Voriconazole and ketoconazole are CI and increase sirolimus concentration
42
Indication of everolimus?
For kidney (low-mod immunologic risk only) or liver transplant
43
Kidney dosing of everolimus?
**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
MOA of CS?
Inhibits of cytokines, IL-1, 2, 3, 6, TNF-a
45
Induction tx of CS?
IV Methylprednisolone, 3 mg/kg
46
Maintenance tx of CS?
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
ADR of CS?
* 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
Types of MMF formulation?
**Mycophenolate mofetil (MMF):** Cellcept prodrug **MPA (Myfortic):** Active drug
49
MOA of MMF?
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
How is MMF metabolized?
Hepatically
51
Dosing MMF?
250mg Cellcept = 180mg Myfortic **Use Myfortic for those who can't tolerate MMF**
52
ADR of MMF?
**GI:** diarrhea, vomiting, ab pain (change formulation) **PML:** infection in brain **Neutropenia, anemia, thrombocytopenia**
53
BBW of azathioprine?
Increase risk of malignancy in humana
54
MOA of belatacept?
Binds costimulatory ligands (CD80 and CD86) on APC preventing interaction with CD28 on T cells
55
Indication and dosing of belatacept?
**Indication:** kidney transplant only **Dosing:** Administered with Basiliximab + MMF + Corticosteroids * Advantages: No CIs
56
ADR of belatacept?
1. Anemia 2. UTI 3. Peripheral edema 4. Constipation 5. N/V 6. Hyperkalemia 7. Hyperpyrexia
57
Toxcity of cyclosporin and tacrolimus?
Nephrotoxcity
58
Toxicity of sirolimus/everolimus?
Myelosuppression
59
Toxicity of MMF, MPA?
Myelosuppression, N/V/D
60
Toxicity of AZA?
Myelosuppression N/V
61
Toxcity of belatacept?
N/V
62
Tx for acute rejection therapy?
**IV steroids:** Methylprednisolone **RATG (thyrmoglobulin):** Antithymocyte globulin **Basiliximab:** IL2-RA **Alemtuzumab:** Anti-CD52
63
Tx options for acute rejection therapy?
1. Increasing the doses of current immunosuppressive drugs 1. Starting “pulse” corticosteroids with subsequent dosage taper 1. Addition of another immunosuppressant indefinitely 1. Short-term treatment with a polyclonal or monoclonal antibody
64
Ex of CS regimen
* Methylprednisolone * High dose 1000mg IV Daily x 3-5 days  * Taper back to maintenance dose of Prednisone PO
65
Infections associated with acute rejection episodes? Tx?
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
INdcations for fungal prophylaxis?
1. LArge blood transfusion 2. Prolonged ICU stay 3. Prior blood spectrum ABX use 4. Known fungal colonization * Lung or heart/lung transplant
67
Tx of HTN complication
Due to CIs, CS, Impaired kidney-graft function **1st line:** CCB (Amlodipine)
68
Tx for HLD complication?
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
What increases the diabetes complications?
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
Overal induction regimen?
**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
Overall maintenance tx?
CsA, Tacrolimus, Sirolimus, MMF, Corticosteroids
71
Overall rejection tx
Glucocorticoid (first line, high dose): IV methylprednisolone ATG or RATG
Therapeutics IV
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