Term
| What is the difference btwn ATGAM and ATG Thymoglobulin |
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Definition
They are both polyclonal antibodies but ATGAM is made human T lymphocytes injected into horses and ATG Thymoglobulin is made from rabbits.
They bind to lymphocytes, granulocytes, bone marrow cells and platelets in humans and attack them and cause marked suppression |
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Term
| What would you use mainly for induction therapy to block small long lived T cells that circulate btwn blood and lymph which primarily impairs delayed hypersensitivity rxn (type IV) which causes marked suppression of cellular immunity to the tissue graft. |
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Definition
| Polyclonal antibodies mainly the rabbit (ATG thymoglobulin) |
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Term
| What is one main adverse effect of polyclonal abs |
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Definition
| xenogenic (animal proteins) that remain on the abs can cause humoral rxn, type III immune response-serum sickness, |
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Term
| What would you use for acute renal allograft rejection or reversal steroid resistant reaction. |
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Definition
Muromonab-CD3
Binds epsilon chain of CD3 component of TCR complex
Initial activation and cytokine release
Then rapid depletion (within minutes) by complement activation-induced cell death and by margination |
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Term
| What can cause cytokine release, acute hypersensitivity rxn, HAMA rxn specially in pts with mouse ab titers of greater than 1:1000, seizures/encephalopathy |
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Definition
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Term
High fever, chills/rigors, headache, tremor, nausea/vomiting, diarrhea, abdominal pain, malaise, myalgias, arthralgias, generalized weakness
Symptoms due to cytokines released by activated T cells and/or monocytes, including TNF-a, IL-2, IL-6, IFNg. This occurs after 30min of drug admin. Worst in 1st dose and
requires pretx with antihistamine, steroids and acetominophen. |
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Definition
| Cytokine release syndrome from use of Muromonab-CD3 |
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Term
| What is the MOA of Daclizumab and Basiliximab? |
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Definition
| They are monoclonal abs (anti IL2R)compet. antag that bind IL2R alpha on activated T cells prevent T cell prolif and activation. DOes not lyse T cells. |
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Term
| If you wanted to use anti IL2R drugs for induction therapy for renal allograft how would you give it? |
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Definition
With GC and cyclosporine (synergy)
Basiliximab can also be given for cardiac or hepatic transplant requires 2 doses (day0 to day 4) while daxlizumab requires 5 doses q 2 weeks (it is discontinued now) |
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Term
| Which adverse effect is lacking in monoclonal abs that muromonab CD3 has. |
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Definition
| Monoclonal abs do not cause cytokine release syndrome and they are not metabolized by the liver so no significant metabolic druf interactions. The other toxicities still apply here. |
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Term
| This drug binds its receptors in the cytoplasm of cells and travel into the nucleus as a transcription factor that inhibits inflammatory genes. The receptors compete with proinflammatory transcription factors for limiting amounts of net effect of alterations in gene expression following corticosteroid treatment results in a down-regulated immune response. |
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Definition
| Glucocorticoids, Their recepts are in many different cells. |
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Term
| In addition to induction, maintenance, acute transplant rejection and GVHD, what is another important use of glucocorticoids? |
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Definition
| Management of cytokine release syndrome |
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Term
impaired immunity, delayed wound healing, diabetes increased plasma cholesterol, increased BP due to more salt retention and mood swings are cause by?
Cushingoid effects |
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Definition
acute adverse effects with higher doses of GCs.
Delayed effects include nuchal fat deposition, weight gain, muscle wasting. osteoporosis |
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Term
| WHat is a substrate of CYP3A4 and P glycoprotein, excreted through biliary excretion and needs to be monitored in pts due to variable absorption. They are also highly protein bound. |
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Definition
| Calcineurin inhibitors like Cyclosporine and Tacrolimus |
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Term
| How do calcineurins inhibitors work? |
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Definition
| cyclosporine and tacrolimus bind to immunophilins (cyclophilin and FK506-binding protein [FKBP], respectively), forming a complex that binds the phosphatase calcineurin and inhibits the calcineurin-catalyzed dephosphorylation essential to permit movement of the nuclear factor of activated •T cells (NFAT) into the nucleus. NFAT is required for transcription of interleukin-2 (IL-2) and other growth- and differentiation–associated cytokines (lymphokines). |
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Term
| In addition to the usual uses of immunosuppresants what are some additional uses of calcineurin inhibitors? Which one is the preferred one to use and why? |
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Definition
1) RA, UC, Crohns, psoriasis, atopic dermatitis. Cyclosporine can be used for uveitis.
Tacrolimus is preferred due to its slightly greater efficacy and less blood level monitoring. |
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Term
| What are the common adverse effects of cyclosporine and tacrolimus |
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Definition
| Nephrotoxicity, Hypertension, Neurotoxicity |
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Term
| Which calcineurin inhibitor causes gun hyperplasia and Hirsutism? |
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Definition
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Term
| Which calcinurin inhibitor causes Hyperglycemia and Hyperkalemia |
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Definition
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Term
| Calcium channel blockers, antifungals, anbiotics (macrolides), GCs, HIV protease inhibitors, grapefruit juice are examples of what? |
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Definition
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Term
| Carbamazepine, Efavirenz (for AIDS), Phenytoin, Phenobarbital, Rifampin, St. Johns wort are examples of? |
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Definition
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Term
| Do not use calcineurin inhibitors with which drugs? |
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Definition
| Drugs of its class and sirolimus, CYP inducers or inhibitors, methotrexate, digoxin |
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Term
| Which antiproliferative drug is also metabolized by CYP3A4, P glycoprotein and also requires close monitoring of blood levels. But this drug is actively taken up by RBCs |
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Definition
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Term
| Explaine the mOA of Sirolimus |
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Definition
Sirolimus-->FKBP-12 complex binds to mTOR--> cell-cycle arrest in the G1--> S phase -->antiproliferative effects
Inhibits deNOVO purine synthesis |
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Term
| What are some unique uses of sirolimus? |
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Definition
Placement of stents would cause a proliferation of cells around the area of stents so this drug inhibits that to keep stent in place longer.
Pts are started on usual maintenance therapy with cyclosporine and gluco and after wound heals they can give sirolumis so no wound healing problems. The nephrotoxicity side effect is dose dep. Of the calcineurin inhibitors, so using it this way prevents that as well. |
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Term
Profound myelosuppression (thrombocytopeni, anemia, leukopenia)
Impaired wound healing, Hepatotoxicity, Diarrhea occur with what toxicity? |
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Definition
Sirolimus
Fluid accumulation, HA, and pneumonitis is also a side effect |
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Term
| Which drug is metabolized into the active 6-mercaptopurine, itself a purine synthesis inhibitor. 6-Mercaptopurine becomes 6thioIMP which is highly toxic and a false nucleotide and impedes DNA synthesis and thus inhibits the proliferation of cells, especially the fast-growing lymphocytes. |
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Definition
Azathioprine.
Some pts have low enzyme levels of TPMT which will also shunt the pathway to the toxic metabolites. |
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Term
| Describe the MOA of Mycophenolate mofetil |
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Definition
| Becomes mycophenolic acid. MPA: potent, selective, noncompetitive, reversible inhibition of inosine monophosphate dehydrogenase (IMPDH) inhibits guanine synthesis de novo purines synthesis |
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Term
| AZA and MPA are both considered ______ and is ______in pregnancy |
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Definition
1) prodrugs
2) teratogenic |
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Term
What is a unique side effect of AZA
What side effect is common in all the immunosuppresants? |
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Definition
Alopecia
Increased risk of infection and malignancy |
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Term
| Allopurinol / Febuxostat inhibit XO--> increases what toxicity? |
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Definition
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Term
| Antacids, drugs that compete for excretion of proximal tubules, and Acyclovir/gancyclovir increase what toxicity? |
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Definition
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