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Transplant Pharmacology (Maintenance Therapy (mTOR Inhibitors: (Sirolimus,…
Transplant Pharmacology
Polyclonal Antibodies
Rabbit antithymocyte antigen (Thymoglobulin): Produced by injecting rabbits with human T cells and harvesting the antibodies
Uses: Induction, treat rejection
MOA: depletion of T lymphocytes. Targets multiple surface antigens resulting in T and some B cell lysis. Binds to other nonlymphoid cells as well, like WBC, RBC, an platelets.
Adverse Effects: Decreased WBC,decreased platelets, infusion related reactions, abdominal pain, nausea, infection, and malignancy
Monoclonal Antibodies
Alemtuzumab: Recombinant, humanized monoclonal antibody
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Uses: Used for B cell CLL and relapsing remitting multiple sclerosis. OFF LABEL for induction therapy for transfusion
Effect: Can result in T cell depletion for up to three years, B cell for 3-12 months, and affects macrophages and monocytes as well and PANCYTOPENIAS
Adverse Effects: Infusion related reactions, nausea, vomiting, rash, hypotension
Basiliximab: Recombinant, chimeric, monoclonal Ab
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Effect: Inhibits proliferation of T cells (doesn't deplete them), which is why its only used for induction
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Maintenance Therapy
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Anti-metabolites
Azathropine
MOA: Prodrug of 6-mercaptopurine. Inhibits purine nucleotide synthesis. This inhibits T and B cell proliferation
Side Effects: Bone marrow suppression, diarrhea, nausea, vomiting, pancreatitis
Drug Interactions: Allopurinol and febuxostate (uric acid lowering meds). This is because both allopurinol and febuxostate inhibit Xanthine oxidase, which is the same enzyme that converts 6-MP to inactive form. MUST LOWER AZATHIOPRINE BUT RECOMMENDED THAT YOU DON"T USE
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mTOR Inhibitors:
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Therapeutic Uses: Calcineurin Inhibitor minimization or withdrawal (gives Kidney's a break) or for persistent acute or chronic rejection to replace CNI or anti-metabolite
MOA: FKBP-12 (same as tacrolimus). The complex binds to mTOR and leads to blockade of IL-2. Arrests cell cycle in G1-S phase, inhibits B and T cell proliferation
Side Effects: Angioedema, edema, WOUND HEALING, hyperlipidemia, proteinuria, and more. NOT WELL TOLERATED
Drug Interactions: Monitor trough levels. Interactions are similar as Calcineurin Inhibitors because they are metabolized in same pathway
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Co-Stimulation Blockers
Belatacept: IV, 30 minute infusion
MOA: Binds to surface of co-stimulatory ligands CD80/CD86 of APC's and interrupts the interaction of CD80 with CD28 on T cells inhibiting T cell activation
Uses: Kidney transplants in conjunction with mycophenolate mofetil and corticosteroids, as well as basiliximab induction
Adverse Effects: Malignancy, primarily CNS. Progressive Multifocal Leukoencephalopathy. CNS infections
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