Transplant Flashcards
Maintenance Therapy for Transplant (Triple Therapy)
1) Antimetabolites (mycophenolate)
2) Calcineurin inhibitors (tacrolimus)
3) Prednisone
-Sirolimus can be used instead of 1 or 2
What are the anti-metabolites?
- Azathioprine
- Mycophenolate
Azathioprine MOA
- Prodrug–> 6-MP
- TPMT and XO enzymes inactivate 6-MP
- dec circulating B and T lymphocytes, dec IG synthesis, dec IL-2 secretion***
Azathioprine Indications
- Prophylaxis organ rejection, active RA
- Off-label: steroid-sparing agent for corticosteroid-dependent IBD, various autoimmune dz (rheum dz)
Azathioprine Monitoring and Interaction
- 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)
Azathioprine ADRs
- N/V, anorexia
- Hepatotox and pancreatitis*
- Myelosuppression* –> bacterial infections w leukopenia, herpes zoster
- Malignancy–> renal transplant has 50-100x RR**
Mycophenolate MOA
dec B and T cell proliferation
Mycophenolate Indications
- Prophy of rejection for renal, cardiac, and hepatic transplant
- Off-label*: tx of lupus nephritis, psoriasis, myasthenia gravis, prevention/tx GVHD
Mycophenolate Monitoring and Interactions
- Monitoring: CBC w diff
- Interactions: other immunosuppressants, Fe, antacids, cholestyramine dec absoprtion**
Mycophenolate ADRs
- NVD, abd cramping common
- Myelosuppression*–> infection often viral
- Miscarriages and birth defects–> BBW***
What are the Calcineurin Inhibitors?
- Cyclosporine
- Tacrolimus
Cyclosporine MOA
-Dec production/release of IL-2 –> inhibits IL-2 induced activation of resting T lymphocytes
Cyclosporine Indications
- Prophylaxis of organ rejection
- Severe, refractory RA, psoriasis, IBD**
- Ophthalmic emulsion** –> inc tear production
Cyclosporine Monitoring and Interactions
- Monitoring: trough levels**, CMP, CBC, BP, FLP
- Interactions: other immunosuppressants, additive nephrotox (gent), substrate of CYP3A4 and PGP**
Cyclosporine ADRs
- Cyclosporenal failure!!!***
- HTN
- Neurotoxicity
- Metabolic abnormalities (glucose, lipids, hyperuricemia)
- Myelosuppression
- Other: gingival hyperplasia**, hirsutism, N/V
Tacrolimus MOA
- Macrolide abx produced by bacteria
- MOA very similar to cyclosporine
Tacrolimus Indications
- Transplant pts
- Refractory UC
- Topical for moderate-severe atopic dermatitis**
Tacrolimus Monitoring and Interactions
- Monitoring: CBC w diff, CMP, BP, [tacrolimus]**
- Interactions: additive nephrotox, substrate of 3A4 and PGP**
Different ADRs b/w tacrolimus and cyclosporine
- More frequent post-transplant DM** (but less severe dysglycemia)
- More frequent alopecia
- Less frequent hirsutism, gingival hyperplasia, HTN
Prednisone MOA
-Prodrug, MOA not fully understood
Prednisone indications, interactions, monitoring
- Indications: prevent and tx of transplant
- Interactions: other immunosuppressants, antagonizes effect of anti-DM meds
- Monitoring: BP, BG/A1C
Prednisone Acute ADRs
- Insomnia
- Nervousness
- Inc appetite
- Hyperglycemia
Prednisone Chronic ADRs (Bolded)
- Cushingoid
- Osteoporosis/AVN
- HPA-axis suppression/growth suppression
- Dose/time dependent myopathy of LE>UE–> proximal muscle weakness, no myalgias or muscle tenderness
Mammalian Target of Rapamycin (MTOR) Inhibitors and MOA
- Sirolimus/Rapamycin
- MOA: inhibits MTOR–> inhibition suppresses cytokine-driven T-cell proliferation**
Sirolimus Indcations
- Transplant pts
- Can take place of calcineurin inhibitor or antimetabolite in triple therapy
Sirolimus Monitoring and Interactions, ADRs
- Monitoring: [Sirolimus}**, CBC w diff, CMP, FLP BP
- Interactions: 3A4 and PGP sub**
- ADRs: similar to tacrolimus
Belatacept
- 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)
