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Immunosuppressive Pharmacotherapy Flashcards

(52 cards)

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1
Q

2 phases of immunosuppressive pharmacotherapy are…

A

1) Induction therapy
2) Maintenance therapy

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2
Q

Risk of acute rejection is highest…

A

In the first 1-3 months after transplant

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3
Q

Induction therapy improves efficacy of immunosuppression by…

A

Reducing acute rejection, and allowing for reduction in other maintenance medications

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4
Q

Induction therapy consists of…

A

IL-2 receptor antagonist or lymphocyte depleting antibody
+
Triple therapy

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5
Q

A common IL-2 receptor antagonist used is…

A

Basiliximab (Simulect)

This is usually standard practice

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6
Q

MOA of IL-2 receptor antagonists is…

A

Binds to IL-2 receptor on activated lymphocytes, preventing IL-2 binding to receptor

Block T-cell pathway, no proliferation

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7
Q

Safety/tolerability of IL-2 receptor antagonists is…

A

Usually well tolerated, no DI’s
Possibility of acute hypersensitivity

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8
Q

Most common lymphocyte depleting antibody is…

A

Anti-thymocyte globulin (ATG, thymoglobulin)

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9
Q

MOA of ATG is…

A

Antibodies will bind to antigens found on surface of T-cells, and depletes T-cells from circulation

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10
Q

Potency of ATG compared to IL-2 receptor antagonists is…

A

Greater - can be used for induction or cell-mediated rejection

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11
Q

Safety/tolerability of ATG is…

A

Bone marrow suppression - platelets/leukocytes may be affected as well
Anaphylaxis, hepatic, infusion related reactions

Think more potent than basiliximab

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12
Q

Dosing for ATG is unique because it is…

A

Weight-based
Lifetime doses are also counted to balance risk vs. immunosuppression

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13
Q

Maintenance immunosuppression regimens usually consist of…

Triple therapy

A

Corticosteroid
Antiproliferative (Mycophenolate, azathioprine)
Calcineurin inhibitors (Cyclosporine, tacrolimus)

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14
Q

MOA of corticosteroids for immunosuppression is…

A

Up-regulates expression of anti-inflammatory proteins, represses expression of proinflammatory proteins

Inhibits antigen presentation, cytokine production, + proliferation of lymphocytes (broad spectrum immunosuppressant)

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15
Q

Dosing of corticosteroids (prednisone) is…

A

Initially IV, then switched to oral prednisone + tapered to lowest effective dose

Usually 5-10 mg/day

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16
Q

Short-term AE’s with prednisone include…

A

Insomnia
Personality changes
GI issues
Glucose alterations

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17
Q

Long-term AE’s with prednisone include…

A

Musculoskeletal changes
Osteoporosis
Cataracts

Are relevant to discuss since usage will be indefinite

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18
Q

To help prevent complications of osteoporosis with long-term prednisone usage, we should…

A

Do routine bone density measurements
Pharmacotherapy - calcium, vitamin D, bisphosphonates

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19
Q

To help prevent complications of hyperglycemia with long-term prednisone usage, we should…

A

Hope it resolves with tapering doses
Modify diet, usage of oral hypoglycemis/insulin if needed

Also consider than tacrolimus may increase BG

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20
Q

Mycophenolate is used more commonly than azathioprine because…

A

Mycophenolate does not affect other rapidly dividing cells

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21
Q

An important drug interaction to remember with azathioprine is…

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A

Allopurinol - risk of myelosuppression, need to dose adjust

22
Q

MOA of azathioprine and mycophenolic acid derivatives is…

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A

Purine analog - affects purine synthesis + metabolism, suppresses T and B cells
Mycophenolate is more specific than azathioprine

23
Q

AE’s of mycophenolate include…

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A

GI - diarrhea, nausea, indigestion
Neutropenia
Anemia

24
Q

When taking mycophenolate, this is required for both males and females…

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A

Birth control - teratogenic

25
Relevant drug interactions with mycophenolate include...
Divalent cations (iron, calcium) Cholestyramine Food - decreases rate, but not extent of absorption ## Footnote Food/drugs can help minimize GI since adherence is super important
26
GI AE's with mycophenolate can be managed via...
Rule out infectious cause Administer with food or acid suppressive medication Divide total daily dose into 3/4 doses, or decrease if possible Try alternate formulation Diarrhea = loperamide if non-infectious Maybe change to azathioprine
27
Neutropenia can be managed via...
Reducing dose if possible Look for other drug causes + eliminate if possible Filgrastim/GCSF if needed (proliferates WBC's)
28
MOA of calcineurin inhibitors (CNI's) | Tacro, cyclo
Forms complex that binds with calcineurin - inhibition of calcineurin impairs expression of several cytokine genes that promotes T-cell activation
29
CNI's require ____ for safety.
Therapeutic drug monitoring - narrow therapeutic index
30
Cyclosporine drug levels can be taken at...
Trough (C0) or 2 hour post dose (C2)
31
Timing of cyclosporine drug levels is important to obtain accurate levels. C0 and C2 timing is...
C2 - no more than 15 minutes from 2 hour mark C0 - 11.5-12.5 hours after last dose
32
Cyclosporine drug levels are dependent on...
Various patient factors - time since transplant, match, AE's, history, type of organ transplant ## Footnote **Individualized levels**
33
An important factor to note about tacrolimus formulations is that...
They are NOT bioequivalent ! Advagraf = once daily dosing Prograf = Q12hours Envarsus is newer and is also once daily
34
Tacrolimus drug levels can be taken at...
Trough level only (C0). No C2
35
Timing of tacrolimus drug levels is important to obtain accurate levels. C0 timing is...
Preferably no more than 30 minutes from the C0 hour mark
36
Tacrolimus drug levels are dependent on...
Various patient factors - time since transplant, match, AE's, history, type of organ transplant ## Footnote **Individualized levels**
37
AE's with CNI's include...
Nephrotoxicity - acute + chronic Neurotoxicity (dose-related), headache, tremor, dizziness, fatigue HTN Electrolyte imbalances GI issues Hepatotoxicity
38
Cyclosporine unique AE's include...
Higher rates of increased lipid levels, BP, and uric acid Hirsutism, acne, gingival hyperplasia unique
39
Tacrolimus unique AE's include...
Higher rates of headache, GI issues (diarrhea), BG levels Alopecia unique
40
HTN, Increased BG, and increased lipid levels from CNI are treated...
Similar to general population With statin, use lowest dose possible and monitor lab values (higher rates of muscle aches/weakness)
41
Notable DI's with CNI's include...
CYP3A4 drugs - most common = erythromycin, clarithromycin, diltiazem, verapamil, antifungals, rifampin, grapefruit juice Avoid if possible - dose adjustment/drug level management if cannot be avoided ## Footnote Take DI's seriously in this population !
42
PD interactions with CNI's include...
NSAID's, nephrotoxic medications Think similar to CKD population
43
Sirolimus is an mTor inhibitor, where the MOA is to...
Engage TOR to **reduce cytokine-dependent cellular proliferation** of G1-S phase of the cell division cycle. Does not block calcineurin ## Footnote Considered "less potent" than a CNI
44
DI's with sirolimus are...
Similar to CNi's
45
mTor inhibitors would be used when...
CNI's cannot be used - declining renal function Malignancy (?anti-tumour properties) Potentially as add-on therapy for those needing increased immunsuppression despite triple therapy
46
Notable AE's with sirolimus include...
Proteinuria Increased BP, lipids Anemia, thrombocytopenia Arthralgia Rash - possibly dose related Mouth sores Edema, non-responsive to diuretic Delayed wound healing ## Footnote If experiencing, may need to reduce dose or just stop drug
47
If a patient experiences acute cellular rejection, we can give...
High dose steroids Antibody therapy - ATG
48
If a patient experiences humoral rejection, we could give...
Plasmapheresis High dose steroids ATG, IV immune globulin Could also give other antibodies directed against B lymphocytes
49
If a patient experiences chronic rejection, we could try...
Increasing maintenance immunosuppression
50
All transplant patients are required to have bloodwork for life - frequency depends on...
Time post-transplant Clinical status of the patient Type of organ transplant
51
Bloodwork assists in monitoring...
For rejection For toxicity from immunosuppressive medications
52
Standard bloodwork consists of...
Drug levels (CNI, mTor) Renal function Hematology/CBC Electrolytes May also include cholesterol panel, etc.

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