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Immunosupressants: What is the MOA of cyclosprine?
cyclosporine (Sandimmune or Neoral) belongs to calcineurin inhibitors, which means it inhibits calcineurin-dependent translocation of cytosolic subunit of nuclear factor of activated T-cells
cyclosporine interacts with what diseases?
- DM (worsens glycemic control)
- (tacrolimus also interacts with DM)
What are some SE of cyclosporine?
CNS(seizure,hallucination, insomnia), gingivial hyperplasia, HTN, hepatotoxic, nephrotoxic, DM, hyperlipidemia, hyperkalemia, hypomagnesemia, hirsutism
What are some drug interactions with cyclosporine? (metabolized by CYP450, 3A)
- CYP3A4 inducers: phenytoin, phenobarbital, carbamazepine, nevaripine, efavirenz, st.john wort, rifampin
- CYP3A4 inhibitors: grape juice, non-dihydropyridines (CCB), azoles, most protease inhibitors
Coadministration of statin (lova, simva,atrovastatin) with cyclosporine does what?
increase HMG-CoA, increased risk of rhabdomyolysis
What is the MOA tacrolimus?
tacrolimus (Prograf) belongs to calcineurin inhibitors; it inhibits translocation of cytosolic subunit of nuclear factor of activated t-cells
What are drug interactions with tacrolimus?
metabolized by CYP450; 3A isoenzymes.. same drug interactions as with cyclosporine
What are some SE of tacrolimus?
CNS(seizure, hallucincations,insomnia),alopecia, HTN, hepatotoxic, DM, nephrotoxic, hyperlipidemia, hyperkalemia, hypomagnesemia, anemia
What is the MOA of sirolimus?
sirolimus (Rapamune) belongs to mTOR inhibitors; it binds to FKBP-12 to form a complex that binds and inhibits activation of its target protein mTOR (mammalian target of rapamycin)
What are the drug interactions with sirolimus?
- metabolized by CYP450;3A isoenzymes.
- same as with cyclosporine and tacrolimus
What are the disease and sirolimus interactions?
liver transplant(increase mortality), lung transplant(fatal bronchical...)
What are the SE of sirolimus?
anorexia, oral ulcers, GI, hyperlipidemia, HTN, hyperkalemia, leukopenia, thrombocytopenia
What drugs belong to calcineurin inhibitors?
cyclosprine and tacrolimus
What drugs belong to antiproliferative agents?
azathioprine, mycophenolate mofetil/sodium
What is the MOA of azathioprine?
azathioprine(Imuran) is a purine analogue prodrug cleaved to mecaptopurine and inhibit synthesis of DNA,RNA, and protein
What are drug interactions with azathioprine?
concominant use with allopurinol will increase effect of azathioprine (when used together decrease dose by 65-75%)
What are disease interactions with azathioprine?
What are SE of azathioprine?
retinopathy, GI, neutropenia, thrombocytopenia
What is the MOA of mycophenolate mofetil?
brand name Cellcept belongs to antiproliferative agents, is metabolized to mycophenolic acid which cause noncompetitive reverse inhibition of inosine monophosphate dehydrogenase (critical enzyme in denovo pathway of purine synthesis) which is crucial during lymphocyte activations and proleferation
What are the drug interactions of mycophenolate mofetil?
cyclosporine, cholestyramine, colestipol and colesevelam, antacids, efficacy of brith control may be decreased
What are disease and mycophenolate mofetil interactions?
severe renal impairment
What are the SE of mycophenolate mofetil?
GI, leukopenia, thrombocytopenia, anemia
What is the MOA of mycophenolate sodium?
brand name is Myfortic, MOA is same as mycophenolate mofetil except it comes in delayed relase tabs. and that delivers the mycophenolic acid
What are drug interactions with mycophenolate sodium?
cholestyramine, antacids, efficacy of birth control may be decreased?
What are the disease and mycophenolate sodium interactions and SE of drug?
same as with mycophenolate mofetil
What IV corticosteroids are used with transplant drugs?
methylprednisolone and dexamethasone
What are oral corticosteroids that are used with transplant drugs?
prednisone, prednisolone, dexamethasone
What are the drug interactions with corticosteroids?
- metabolized by CYP450;3A isoenzymes
- same as with cyclosprine and tacrolimus
What are disease and corticosteroids interactions?
DM, osteopenia, osteoporosis
What are some SE with corticosteroids?
CNS(ex.insomnia), HTN, edema, DM, hyperlipidemia, growth supression, hirsutism, myopathy, and osteoporosis
What drugs belong to monoclonal antibodies class?
muromonab-CD3, basiliximab, daclizumab
What premedications need to be given before IV bolus orthoclone (muromonab-CD3)?
IV steroids, tylenol, antihistamines 1hr. prior to dose
What needs to be assessed prior to dose of orthoclone?
volume status (pt. with volume overload or uncompensated CHF (coronary heart failure) should not get this drug)
What are the SE of orthoclone?
dizzy, HA, photophobia, tachycardia, tremor, pulmonary edema
What are the SE of basiliximab(Simulect)-(Ig6) or daclizumab(Zenapax)?
hypersensitivity, including anaphylaxis
What drugs belong to polyclonal antibodies?
- antithymocyte globulin(equine) (Agam)
- antithymocyte globulin(rabbit) (hymoglobulin)
What drugs need to be given before polyclonal antibodies?
IV steroids,tylenol, antihistamine 1hr prior to dose
What are SE and monitoring of polyclonal antibodies?
- infusion related reactions(fever,chills,dypnea), leukopenia, thrombocytopenia
- Monitoring: goal for tx. of acute rejection is supression of CD3 lineage to <50cells/mm3
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