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Clinical Pharmacology Exam 3 > Transplant > Flashcards

Transplant Flashcards

1
Q

Maintenance Therapy for Transplant (Triple Therapy)

A

1) Antimetabolites (mycophenolate)
2) Calcineurin inhibitors (tacrolimus)
3) Prednisone

-Sirolimus can be used instead of 1 or 2

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2
Q

What are the anti-metabolites?

A
  • Azathioprine

- Mycophenolate

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3
Q

Azathioprine MOA

A
  • Prodrug–> 6-MP
  • TPMT and XO enzymes inactivate 6-MP
  • dec circulating B and T lymphocytes, dec IG synthesis, dec IL-2 secretion***
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4
Q

Azathioprine Indications

A
  • Prophylaxis organ rejection, active RA

- Off-label: steroid-sparing agent for corticosteroid-dependent IBD, various autoimmune dz (rheum dz)

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5
Q

Azathioprine Monitoring and Interaction

A
  • Monitoring: CBC w diff, CMP, TPMT genotype/phenotype
  • Interactions: additive immunosuppressants, ACEI* (may induce anemia/severe leukopenia), allopurinol/febuxostat* (inhibits XO, slows eliminating of 6-MP)
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6
Q

Azathioprine ADRs

A
  • N/V, anorexia
  • Hepatotox and pancreatitis*
  • Myelosuppression* –> bacterial infections w leukopenia, herpes zoster
  • Malignancy–> renal transplant has 50-100x RR**
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7
Q

Mycophenolate MOA

A

dec B and T cell proliferation

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8
Q

Mycophenolate Indications

A
  • Prophy of rejection for renal, cardiac, and hepatic transplant
  • Off-label*: tx of lupus nephritis, psoriasis, myasthenia gravis, prevention/tx GVHD
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9
Q

Mycophenolate Monitoring and Interactions

A
  • Monitoring: CBC w diff

- Interactions: other immunosuppressants, Fe, antacids, cholestyramine dec absoprtion**

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10
Q

Mycophenolate ADRs

A
  • NVD, abd cramping common
  • Myelosuppression*–> infection often viral
  • Miscarriages and birth defects–> BBW***
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11
Q

What are the Calcineurin Inhibitors?

A
  • Cyclosporine

- Tacrolimus

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12
Q

Cyclosporine MOA

A

-Dec production/release of IL-2 –> inhibits IL-2 induced activation of resting T lymphocytes

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13
Q

Cyclosporine Indications

A
  • Prophylaxis of organ rejection
  • Severe, refractory RA, psoriasis, IBD**
  • Ophthalmic emulsion** –> inc tear production
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14
Q

Cyclosporine Monitoring and Interactions

A
  • Monitoring: trough levels**, CMP, CBC, BP, FLP

- Interactions: other immunosuppressants, additive nephrotox (gent), substrate of CYP3A4 and PGP**

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15
Q

Cyclosporine ADRs

A
  • Cyclosporenal failure!!!***
  • HTN
  • Neurotoxicity
  • Metabolic abnormalities (glucose, lipids, hyperuricemia)
  • Myelosuppression
  • Other: gingival hyperplasia**, hirsutism, N/V
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16
Q

Tacrolimus MOA

A
  • Macrolide abx produced by bacteria

- MOA very similar to cyclosporine

17
Q

Tacrolimus Indications

A
  • Transplant pts
  • Refractory UC
  • Topical for moderate-severe atopic dermatitis**
18
Q

Tacrolimus Monitoring and Interactions

A
  • Monitoring: CBC w diff, CMP, BP, [tacrolimus]**

- Interactions: additive nephrotox, substrate of 3A4 and PGP**

19
Q

Different ADRs b/w tacrolimus and cyclosporine

A
  • More frequent post-transplant DM** (but less severe dysglycemia)
  • More frequent alopecia
  • Less frequent hirsutism, gingival hyperplasia, HTN
20
Q

Prednisone MOA

A

-Prodrug, MOA not fully understood

21
Q

Prednisone indications, interactions, monitoring

A
  • Indications: prevent and tx of transplant
  • Interactions: other immunosuppressants, antagonizes effect of anti-DM meds
  • Monitoring: BP, BG/A1C
22
Q

Prednisone Acute ADRs

A
  • Insomnia
  • Nervousness
  • Inc appetite
  • Hyperglycemia
23
Q

Prednisone Chronic ADRs (Bolded)

A
  • Cushingoid
  • Osteoporosis/AVN
  • HPA-axis suppression/growth suppression
  • Dose/time dependent myopathy of LE>UE–> proximal muscle weakness, no myalgias or muscle tenderness
24
Q

Mammalian Target of Rapamycin (MTOR) Inhibitors and MOA

A
  • Sirolimus/Rapamycin

- MOA: inhibits MTOR–> inhibition suppresses cytokine-driven T-cell proliferation**

25
Q

Sirolimus Indcations

A
  • Transplant pts

- Can take place of calcineurin inhibitor or antimetabolite in triple therapy

26
Q

Sirolimus Monitoring and Interactions, ADRs

A
  • Monitoring: [Sirolimus}**, CBC w diff, CMP, FLP BP
  • Interactions: 3A4 and PGP sub**
  • ADRs: similar to tacrolimus
27
Q

Belatacept

A
  • MOA: T-cell blocker
  • Indications: prevent rejection of renal transplant in EBV + pts
  • Interactions: other immunosuppressants
  • ADRs: leukopenia, NVD, anemia, inc risk malignancy, post-transplant lymphoproliferative disorder (PTLD)

Clinical Pharmacology Exam 3 (19 decks)

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