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PHRM 865 Final > Transplant > Flashcards

Transplant Flashcards

(46 cards)

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1
Q

Multidisciplinary Transplant Evaluation Process

A

Medical
Pharmacy
Immunologic

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2
Q

Pre-transplant Immunologic Evaluation

A

Make sure the donor and recipient are the same blood type

Based on ABO blood group antigens

OB: universal donor, no antigens
AB: universal recipient, no antibodies

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3
Q

Major Histocompatibility complex (MHC)/Human Leukocyte Antigen (HLA)

A

An association of genes found on short arm of chromosome 6 that play an important role in immune recognition and response

Distinguishes “self” from “non-self”

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4
Q

What is a potential contraindication to transplant?

A

Pre-transplant HLA donor-specific antibodies

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5
Q

Determination of PRA (Panel Reactive Antibodies)

A

Desire a low PRA

The higher the PRA= increased sensitization to MHC antigens and increased risk of rejection and longer wait times

PRA can be checked multiple times while on waitlist: possible “sensitizing events”

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6
Q

Goals of Immunosuppressive Therapy

A

Balance:
Rejection
Toxicity
Infection

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7
Q

Risk of rejection

A

Risk increases with more lymphoid tissue

Liver<kidney/pancreas<hear<small bowel, lung

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8
Q

Hyperacute rejection

A

occurs within minutes to hours after

mediated by preformed circulating antibodies

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9
Q

Acute rejection

A

occurs within days to months after

mediated by T-cells

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10
Q

Chronic rejection

A

months to years after

both cellular-mediated and antibody processes appear to be involved

progressive decline in organ function

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11
Q

Under-immunosuppression

A

risk rejection

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12
Q

Over-immunosuppression

A

risk infection, toxicity, malignancy

combination therapy to maximize immunosuppression with overlapping/synergistic mechanism

Individualize therapy!

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13
Q

Induction therapy

A

intense prophylactic therapy at time of transplant

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14
Q

Maintenance therapy

A

long-term, chronic immunosuppression given after transplant

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15
Q

Rejection therapy

A

most intense therapy utilized in response to a rejection episode

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16
Q

Induction agents

A

Polyclonal antibodies:
- Thymoglobulin, horse antithymocyte globulin

Monoclonal antibodies:
- alemtuzumab

IL-2alpha receptor antagonists:
- basiliximab

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17
Q

Thymoglobulin

A

Induction therapy

T1/2= 30 days
Lymphocyte depletion persisting for 3 months

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18
Q

Thymoglobulin side effects

A

Leukopenia, Thrombocytopenia:
- dose-limiting

Fever, chills
- pre-medicate with diphenhydramine and Tylenol

Monitor WBC, ALC, platelets, vital signs

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19
Q

Alemtuzumab (Campath)

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A

off-label use in SOT as induction

Profound depletion of T cells, can persist for up to 12 months

20
Q

Alemtuzumab side effects

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A

Infusion-related: chills, rigors, fever:
- pre-medicate with diphenhydramine and Tylenol

Monitor WBC, ALC, platelets, vital signs

21
Q

Basiliximab

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A

Induction only

NON-lymphodepleting: will not knock out B and T cells

22
Q

Choosing an induction agent

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A

Varies by organ

Lymphocyte depleting therapy is more commonly used

Basiliximab is reserved for some patient specific factors:
- malignancy
- immunocompromised
- HIV, untreated HCV
- > 65

23
Q

Calcineurin Inhibitors

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A

Cornerstone of immunosuppression

Maintenance therapy

24
Q

Sandimmune (Cyclosporine)

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A

Non-modified CNI

25
Neoral and Gengraf (Cyclosporine)
Modified microemulsion Improved bioavailability
26
Tacrolimus (FK)
Formulations: - Immediate-release: Prograf - Extended-Release: Astagraf XL, Envarsus XR - Potential benefits to ER dosing: lower overall drug dose, improved adherence, less peak effects= reduced ADE, less swings/variability in trough concentrations DIFFERENT conversions for IR vs ER
27
Cyclosporine (CsA) metabolism
CYP3A4 and P-glycoprotein-->increase exposure drug-drug interactions
28
Cyclosporine (CsA) elimination
T1/2 highly variable (10-40 hr) Prolonged in hepatic disease or disorders of biliary excretion
29
Cyclosporine adverse effects
Hypertension Hypercholesterolemia Hypertriglyceridemia Gingival Hyperplasia Hirsutism
30
Tacrolimus adverse effects
Neurotoxicity: HA, insomnia, tremor, dizziness Hyperglycemia; post-transplant DM Alopecia
31
CYP450 inducers= decrease CSA/FK concentrations
Phenytoin Carbamazepine Phenobarbital Rifampin
32
CYP450 inhibitors= increase CSA/FK concentrations
Ethromycin, clarithromycin Azoles Diltiazem, verapamil Ritonavir Grapefruit juice
33
Liver dysfunction-->alterations in CNI PK
Tacrolimus eliminated by hepatic metabolism T1/2 prolonged
34
Renal dysfunction--> no change in CNI PK
Very minimal excretion of drug Dose adjustments not necessary for patients receiving forms of renal replacement
35
Azathioprine (AZA) adverse effects
Gi: abdominal pain, N/V, diarrhea, dyspepsia Bone marrow suppression: agranulocytosis, microcytic anemia, leukopenia, neutropenia, thrombocytopenia
36
Mycophenolic Acid (MPA)
Most commonly used adjunct agent with CNIs (tacrolimus)
37
Mycophenolic Acid (MPA) dosing
Therapeutically equivalent and interchangeable but dosing requires conversion MMF 250 mg=MPS 180 mg IV: PO 1:1
38
Mycophenolic Acid adverse effects
N/V/D FDA pregnancy category D (teratogenic) 2 forms of birth control required Drug interactions: valganciclovir, sirolimus
39
mTOR inhibitors: Sirolimus, Everolimus
Metabolism: CYP3A4, and Pgp Same DDI and CNIs
40
Sirolimus
Approved for kidney transplant rejection prophylaxis
41
Everlimus
Approved for kidney and liver transplant rejection prophylaxis
42
Sacrolimus and Everlimus adverse effects
Edema hyperlipidemia hypertriglyceridemia IMPAIRED WOUND HEALING mouth ulcers proteinuria
43
Coticosteroids
The "original" cornerstone of therapy Some centers utilize early steroid withdrawal or steroid-free regimens
44
Corticosteroids adverse effects
ADE related to both average dose and cumulative duration of use
45
Belatacept
Relative contraindication for use in liver transplant dose: routinely q4weeks at an infusion clinic Replacement or adjunct to CNI AE: contraindicated in EBV seronegative patients
46
Triple drug regimen
CNI: Tacrolimus Antimetabolite: Mycophenolate +/- corticosteroid

PHRM 865 Final (3 decks)

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