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Therapeutics P3 Spring > Solid organ transplant management > Flashcards

Solid organ transplant management Flashcards

(75 cards)

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1
Q

What are transplantable solid organs or “allografts”

A

Heart
Lung
Liver
Kidney
Pancreas
Small bowel

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2
Q

Define autotransplantation, allotransplantation, xenotransplantation, orthrotopic, heterotopic

A

Autotranspntation- Transplant of tissue from 1 part of body to another

Allotransplantation- transplant of tissue from 1 person to another person

Xeno- transplant from different species

Heterotopic- Transplanted into recipient in a different place (ex kidney)

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3
Q

WHat are some living and deceased organ donors

A

liver- kidney or livers, related or unrelated, directed or non directed, kidney paired exchange

Deceased by brain death (primarily brain death with organs still perfused.)

Deceased by circulatory death (DCD)- does not meet brain death criteria, non heart beating donation

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4
Q

What are some pre transplant immunologic evaluations and managements

A

ABO blood type matching
Major histocompatibility complex (MHC)/ Human leukocyte antigen (HLA) complex

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5
Q

How are HLA antibodies formed

A

Formed in response to non self HLA exposure.

do NOT occur naturally

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6
Q

What are the two types of antibodies formed in transplants? Describe them

A

pre- transplant HLA donor specific antibodies (DSA)= contraindicated in deceased donor transplants

Post transplant DSA- development indicates failure of immunosuppression (denovo DSA)

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7
Q

What are sensitizing events that could cause HLA antibodies

A

Blood transfusions, pregnancy, previous transplants, sensitizing events

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8
Q

What is PRA? describe it?

A

Panel reactive antibodies- Quantified as % of the panel to which the patient has developed antibody.

Value varies from 0-100% and may change over time

Higher the PRA= increased sensitization to MHC antigens

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9
Q

What is a test other than PRA that must be done before transplant? MOA?

A

Determination of crossmatch
(negative result must be obtained prior to transplant)

Testing the transplant recipients serum against donor T cells to determine if there is a performed anti HLA class I antibody

positive XM means high risk of rejection

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10
Q

What is an allograft rejection? What can it lead to? What cells can it occur in

A

Immune response causing inflammation and direct tissue destruction

Ultimately can lead to loss of graft function/

Can occur in T cells, B cells or both

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11
Q

Risk of rejection with different organs

A

Risk increases with more lymphoid tissue

Liver is lowest
Kidney, pancreas
heart
Small bowel is highest

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12
Q

recipient characteristics that have risk of rejection

A

Younger, higher risk (immune system is strong in youngers)

Race (african americans tend to have greater risk for rejection)

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13
Q

Types of allograft rejection

A

T cell mediated rejection (TCMR) (acute cellular rejection

Antibody mediated rejection (B cell mediated rejection)

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14
Q

timeline of rejection for transplant? What cells is it mediated by?

A

Hyperacute rejection- occurs within minutes-hours (mediated by circulating antibodies)

Acute rejection- Days- months (mediated by T cells)

Chronic- months- years (both cellular and antibody)

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15
Q

WHat does underimmunosuppression look like? Over immunosuppression

A

Under- rejection

Over- infection, toxicity, malignancy

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16
Q

Define induction, maintenance and rejection therapy.

A

Induction therapy- intense prophylactic therapy at time of transplant given to lower incidence of rejection and delay use of aintenance agents

Maintenance- long term, chronic immunosuppression given after transplant

rejection therapy- most intense therapy utilized in response to rejection episode

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17
Q

What are the 3 classes of induction agents? What are some drugs in those classes

A

Poly clonal antibodies- thymoglobulin, ATGAM

Monoclonal antibodies- alemtuzumab

IL-2 antagonists- basiliximab

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18
Q

indication for thymoglubulin? MOA?

A

Induction and/or rejection therapy

Reduces number of circulating T lymphocytes, which alters T cell activation, homing, cytotoxic

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19
Q

How long dioes thymoglobulin last? How long does lymphocytes depletion last

A

half life is 30 days
Lymphocyte depletion lasts 3 months

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20
Q

Adverse effects of thymoglobulin? Dose limiting side effects?

A

Leukopenia, thrombocytopenia are dose limiting

Fevers, chills (we pre medicate with diphenhydramine and acetaminophen)

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21
Q

What type of antibody is alemtuzumab

A

Anti-CD52 monoclonal antibody

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22
Q

MOA of alemtuzumab

A

Profound depetion of T cells to a lesser degree B cells and monocytes

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23
Q

Adverse effects of alemtuzumab

A

Infusion related chilld, rigors and fever

pre medicate with diphenhydramine and acetaminophen

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24
Q

MOA of basiliximab

A

NON lymphocyte depleting

Competitively inhibits IL2 activation of lymphocytes

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25
Name monoclonal deplting drug? Polyclonal depleting? Monoclonal non depleting
Monoclonal depleting- a;emtuzumab Polyclonal depleting- thymoglobulin Monoclonal non depleting- basiliximab
26
WHen is basiliximab reserved for?
for patients with - history of malignancy - HIV, untreated HCV -High infection risk, immunocompromised - advanced age (>65)
27
for patients with high immunologic risk, what do we use
Lymphocyte depleting therapy
28
What are the different maintenance agents? Name the drugs under them
Calcineurin inhibitors- cyclosporine, tacrolimus (most important) Antimetabolites- azathioprine, mycophenolate mofetil, mycophenolate sodium mTOR inhibitors- Sirolimus, everolimus Corticosteroids- methylprednisolone, prednisone, dexamthasone T cell co stimulation blocker- belatacept
29
MOA of calcineurin inhibitors?
Cornerstone of immunosuppresion. MOA- induces immunosuppression by inhibiting signal of T cell activation. prevents subsequent T cell activation
30
WHat are the different formulations of cyclosporine? are thhey interchangeable?
Non modifable- poor and erratic bioavailability Modified- improved bioavailability NOT onterchangeable
31
what to know about target trough for cyclosporine
Target trough- 100-400 Trough target higher in initial post transplant period then decreased over time
32
what are the different formulations of tacrolimus? Which is better
IR and ER formulations ER formulation has lower overall drug dose, imoroved adherence, less peak effects, reduced ADE, less swings/variability in trough concentrations
33
what are some conversions for dosing tacrolimus
Conversion to sublingual (SL)= 2:1 (4 mg PO = 2 mg SL) COnversion to IV typically 5:1= 2 mg IV = 10 mg PO
34
is tacrolimus more potent or is cyclosporine more potent (exam) and goal 12 h trough range (exam)
tacrolimus 50 x more potent than cyclosporine Goal 12- Hr trough range is 5-15
35
name the IR and ER drugs of tacrolimus
prograf- IR Astagraf and envarsus- ER Not 1:1 conversion between drugs
36
compare the metabolism and elimination of tacrolimus and cyclosporine
Metabolism of cyclosporine is cyp3A4 AND P-glycoprotein metabolism. Metabolism of tacrolimus is just CYP3A4 both prone to multiple drug interactions Elimination of cyclosporine half life is highly variable (10-40 hr) Tacrolimus is more consistent at 12-18 hrs
37
name cyp450 inducers that decrease CSA/FK concentrations? Name cyp450 inhibitors that increase CSA/FK concentrations
Inducers that decrease concentrations- Phenytoin, rifampin, phenobarbotal, rifampin Inhibitors that increase CSA/FK concentrations- Erythromycin, clarithromycion, azoles, diltiazem, verapamil, ritonavir, grapefruit juice
37
adverse effects of cyclosporine and tacrolimus compare
Cyclosporine- HTN, Hypercholesterolemia, hypertriglyceridemia, gingival hyperplasia, hirsutism Tacrolimus- Neurotoxicity (headache, insomnia, tremor, dizziness), Hyperglycemia, post transplant diabetes mellitus, alopecia
38
would liver dysfunctions affect CNI PK? What about renal dysfunction? how would they affect them? (exam)
Liver dysfunction- tacrolimus primarily eliminated by hepatic metabolism. T 1/2 prolonged Renal- no change in CNI PK. very minimal urinary excretion of drug. Dose adjustment not necessary in renal dysfunction
39
name antimetabolites that can be used as maintenance immunosuppression
azathioprine, mycophenolate mofetil, ,ycophenolate sodium
40
MOA of azathioprine
AZA converted into 6-MP in blood 6-MP incorporated into nucleic acids Inhibition of RNA and DNA synthesis Inhibition of immune cell proliferation
41
What is the conversion of azathioprine from PO to IV? dosing? monitoring?
1:1 ratio PO dosinh 1-3 mg/kg/day administered QD no routine TDM
42
adverse effects of azathioprine
GI abdominal pain, N/V., diarrhea, dyspepsia Bone marrow suppression, agranulocytosis, macrocytic anemia, leukopenia, neutropenia, thrombocytopenia Rapid cells
43
Drug interactions of azathioprine (exam(
Allopurinol and febuxostat reduce AZA by 50-75%
44
What is mycophenolic acid (MPA) usually used as
Most commonly used adjunct agent with CNIs
45
MOA of mycophenolic acid
Inhibits the de novo, pathway of purine synthesis, selective for lymphocytes This limits progression of T and B cells
46
What are the two mycophenolic acid drugs? What is their difference?
Mycophenolate mofetil- Pro drug, IR Mycophenolate sodium- enteric coated, delayed release
47
Conversion of mycophenolate mofetil and sodium? Are they therapeutically eqivalent?
Therapeutically equivalent and interchangeable Mofetil 250 mg = sodium 180 mg
48
adverse effects of mycophenolic acid
FDA pregnancy category $ (teratogenic) Part of the REMS program as well as 2 forms of birth control
49
Drug interactions of mycophenolic acid
Other myelosuppression drugs such as valganciclovir,sirolimus (additive myelosuppression)
50
What are mTOR inhibitors
sirolimus, everolimus
51
Metabolism of mTOR inhibitors
CYP 3A4 and PGP same as DDI and CNIs
52
WHat are sirolimus and everolimus approved for?
sirolimus- kidney transplant everolimus- kidney and liver transplant
53
advrese effects of sirolimus and everolimus (exam)
both- edema, hyperlipidemia, hypertriglyceridemia, impaired wound healing, mouth ulcers, proteinuria
54
why is mTOR not used immediately post transplant
causes impaired wound healing
55
limitations of sirolimus and everolimus
sirolimus- increased risk of heaptic artery thrombosis post op Everolimus- increased risk of kidney arterial and venous thrombosis post op
56
What are the various roles of mTOR
replace CNIs in patients with nephrotoxicity In combo with CNIs to use lower lovels of both drugs replace mycophenolate in pts with intolerable ADE (nausea) steroid free protocols
57
when would we switch from mycophenolate to sirolimus
Ongoing nausea
58
ADE of corticosteroids
ADE related to both average dose and cumulative duration of use HTN, hyperglycemia, bone fractures/osteoporosis, weight gain, GI disturbances, wound healing
59
Name a T cell co stimulation blocker
belatacept
60
contraindication of belatacept
relative contraindication for use in liver transplant
61
ROA of belatacept? Place in therapy?
Routinely q 4 WEEKS AT AN INFUSION CLINIC Replacement or adjunct to CNI
62
COntraindication of belataceot
contraindicated in EBV seronegative patients
63
most common regimen prescribed for patients
calcineurin inhibitor (like tacrolimus/cyclosporine) + Antimetabolite (mycophenolate, azathioprine) +/- corticosteroid (prednisone)
64
What are other immunosuppressive regimen? apprach and rationale for using them?
Approach- CNI avoidance/minimization, rationale: Improved renal function example regimens- sirolimus +mycophenolate or azathioprine + corticosteroids everolimus + low dose tacrolimus + corticosteroids Belatacept + mycophenolate + cortiosteroids apprach- corticosteroid withdrawal or avoidance (rationale- goal to decrease long term associated toxicity)
65
what do we use of someone has acute cellular rejection (mild- moderate? Moderate- severe? Refractory?)
Mild-moderate- high dose corticosteroids moderate-severe or steroid resistant- T lymphocyte depleting therapy refractory- alemtuzumab
66
what to use for antibody mediated rejection (AMR)
steroids+/- rituximab+/- IVIG
67
Indication of rituximab
off label use in Solid organ transplant - desensitization protocols (transplant recipients with anti-HLA class I and/or II antibodies against donor and/or ABO incompatible transplantation) - treatement of antibody mediated rejection
68
adverse effects of rituximab
first dose- infusion rxn complex (pre medicate with diphenhydramine, methylprednisolone)
69
IVIG (intravenous immune globulin) indication
desensitization protocols in SOT. treatment of antibody mediated rejection
70
adverse effects of IVIG? monitoring?
infusion related (fevers, chills, flushing)- premedicate with acetaminophen and diphenhydramine vital signs prior to staret of infusions, before increase of dose and end
71
when using tacrolimus and creatinine is trending upwards what do we do?
It is showing acute cellular rejection. Tacrolimus could cause possible CNI induced nephrotixicity methylprednisolone 500 mg x 3 days used
72
common infections in solid organ transplants without prophylacis
Pneumocystitis, HSV, VZV, CMV, EBV, HBV listeria, toxoplasma, nocardia, leishmania
73
what do we use for pcp and pjp prophylaxis in solid organ transplant pts
TMP-SMX (atovaquone, dapsone or pentamidine used if allergic)
74
fungal prophylaxis for solid organ tansplant pts (especially in lung)
posaconazole

Therapeutics P3 Spring (33 decks)

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