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Cology 2 Exam 3 > Immunosuppressants 3: 17-34 > Flashcards

Immunosuppressants 3: 17-34 Flashcards

1
Q

What is the difference between Basiliximab and Daclizumab?

A

Basiliximab is from chimeric mouse; not used much

Daclizumab is humanized

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2
Q

What do IL-2 receptor antagonists work against?

A

Antibodies against IL-2 CD25 receptors on activated T-cells

Prevent activated T-cell killing but does NOT deplete T-cells, mechanism is not completely understood

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3
Q

What are the IL-2 receptor antagonists?

A

Basiliximab and Daclizumab

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4
Q

What are IL-2 receptor antagonists used for?

A

Prophylaxis of acute rejection, maintenance immunosuppression

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5
Q

Adverse effects of IL-2 receptor antagonists?

A

Hematological, infections, anaphylactic reactions

Usually well tolerated

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6
Q

What are the Calcineurin inhibitors?

A

Cyclosporine (IV and Oral)

Tacrolimus (preferred) (IV and Oral)

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7
Q

What is cyclosporine used for?

A

Liver, heart, kidney and other transplants
Rheumatoid arthritis and psoriasis
Also maintenance suppression

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8
Q

How does Cyclosporine work?

A

Calcineurin inhibitor; inhibits mRNA transcription of IL-2, binds cyclophilin to inhibit calcineurin
Prevents NF-AT from stimulating IL-2 transcription

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9
Q

Adverse effects of cyclosporine?

A

Constriction of afferent artery at glomerulus, renal dysfunction (majority of pts)
P-glycoprotein transport in BBB can cause tremor
Hypertension (50% of renal patients, all heart transplants)
Diabetogenic esp with glucocorticoids
CYP3A interactions (increase or decrease levels)

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10
Q

How does Tacrolimus work?

A

Binds FK binding protein to inhibit actions of Calcineurin, prevents NF-AT activating IL-2 transcription

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11
Q

How is Tacrolimus administered?

A

Oral and IV

Food decreases absorption!

Protein bound

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12
Q

What is Tacrolimus used for?

A

Maintenance suppression and rescue in acute rejection

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13
Q

Adverse effects of Tacrolimus?

A 
Nephrotoxicity
Neurotoxicity (tremor, headache, seizures)
GI
Hypertension
Hyperglycemia
Tumors
Secondary infections

Damages pancreatic beta cells –> diabetes

CYP3A4 metabolism affected

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14
Q

Between CyA and Tac, which one has the highest nephrotoxicity?

A

Same (+++)

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15
Q

Between CyA and Tac, which one has the highest hyperglycemia?

A

Tac

CyA is ++, Tac is +++

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16
Q

Between CyA and Tac, which one has the highest metabolic complications?

A

Same (+++)

17
Q

Between CyA and Tac, which one has the highest hypertension?

A

Same (+++)

18
Q

Between CyA and Tac, which one has the highest neurotoxicity - CNS tremors?

A

Same (++)

19
Q

Between CyA and Tac, which one has the highest neurotoxicity - Disorientation?

A

Tac (+++)

CyA is ++

20
Q

Between CyA and Tac, which one has the highest Hirsutism?

A

CyA (++)

Tac has none!

21
Q

Between CyA and Tac, which one has the highest Alopecia?

A

Tac (++)

CyA has none

22
Q

What agents target Rapamycin (mTOR) inhibitors?

A

Sirolimus

Everolimus

23
Q

How does Sirolimus work?

A

Binds to FKB-12 and inhibits mTOR stimulated cell proliferation at G1-S phase transition

24
Q

How is Sirolimus metabolized?

A

CYP3A4 metabolism, there are 7 major metabolites

25
Q

How is Sirolimus administered?

A

Oral only

26
Q

When is Sirolimus used?

A

For Acute RENAL transplants only (not used in liver and lung transplants because of bronchial and hepatic artery stenosis)

Prophylaxis - used to limit use of calcineurin inhibitors

Heart stents to prevent proliferation effects (prevent cells growing on the stent)

27
Q

Adverse effects of Sirolimus?

A

Dyslipidemia - cholesterol and TG’s treat
Thrombocytopenia
Wound healing - use lymphoceles, wait 1 month after transplant to start therapy
Interstitial pneumonitis, pulmonary infections
Lymphoma
Bone marrow suppression

28
Q

How does Everolimus compare to Sirolimus?

A 
Approved for renal transplants and liver transplants
Chemically related
SHORTER half life
Shorter time to steady state
Actions are very similar

Both used together increase renal toxicity but also decrease rejection (usually not used together though)

29
Q

What agents are used Pre-operatively?

A

Antibodies

30
Q

What agents are used intra-operatively?

A

Methylprednisolone

31
Q

What agents are used post-operatively?

A

Calcineurin inhibitor (Cyclosporine or Tacrolimus) + Glucocorticoid + Anti-metabolite (Mycophenolate mofentil or Azathioprine)

Sirolimus is also used to delay use of calcineurin inhibitors

32
Q

What options do we have if a patient has rejection?

A 
Alter maintenance regimen
Methotrexate
Plasmapheresis (for vascular rejection)
Total lymphoid irradiation
Re-transplantation
33
Q

How can we alter maintenance regimen if rejection occurs?

A

Change cyclosporine to tacrolimus
Change mycophenolate mofentil to azathioprine
Change Azathioprine to cyclophosphamide

Cology 2 Exam 3 (11 decks)

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