Cellular Suppression Flashcards
1
Q
Cyclosporine
A
- Class/MOA: Calcineurin inhibitors: prevent transcription of IL-2 leading to decreased T cell activation (binds cyclophilin –> NFAT not dephosphorylated –> no transcription)
- Kinetics: Poor and variable bioavailability, narrow therapeutic range, metabolized by CYP3A4
- SE: Renal toxicity, HTN, hyperglycemia/hyperlipidemia, CNS tremor, gingival hyperplasia
- CI: watch out with CYP inducers and inhibitors!
- Uses: prevent rejection and maintenance after transplant, AI diseases
2
Q
Tacrolimus
A
- MOA: calcineurin inhibitor, prevents transcription of IL-2 leading to decreased T cell activation (binds FKBP)
- Kinetics: IV/Oral/topical. Must be taken on empty stomach as food interferes w/absorption. Narrow therapeutic range, metabolized by CYP3A4.
- SE: more tolerable than cyclosporine, SE are the same just lessened: Renal toxicity, HTN, hyperglycemia, CNS effects, insomnia
- CI: watch out for CYP inducers/inhibitors. Caution with ACE/ARBs, don’t combine with aminoglycosides
- Uses: Prevent rejection especially with liver, kidney, and heart. Cream for atopic dermatitis.
- Other: long term use increases opportunistic infections and neoplasms (esp skin cancer)
3
Q
Pimecrolimus
A
- Like tacrolimus, binds FKBP-12
- Cream for atopic dermatitis, does not thin skin/cause atrophy like steroids
- SE: skin irritation or burning
4
Q
Belatacept
A
- MOA: Blocks costimulatory molecules of APCs –> prevents T-cell stimulation and proliferation.
- Injection only, must be combined with mycophenolate mofetil
- SE: better CV profile and less risk of diabetes than cyclosporine. GI and infusion related SE are most common.
- Used in kidney transplants only if EBV positive
5
Q
Sirolimus
A
- MOA: blocks response of T-cells to IL-2, inhibits B cell proliferation
- Oral absorption (significantly reduced by food), CYP3A4 metabolism
- SE: no renal toxicity, increases cholesterol and triglycerides, profound myelosuppression (anemia/leukopenia), impair wound healing, possible hepatotoxicity.
- Uses: Kidney transplant, prevent graft v. host in stem cell.
6
Q
Mycophenolate Mofetil
A
- MOA: inhibits inosine monophosphate dehydrogenase –> prevents de novo purine synthesis (specific to T/B cells since other cells have salvage), suppresses lymphocyte proliferation and ab production by B cells.
- Kinetics: well absorbed orally, 90% renal excretion, prodrug that is converted to mycophenolic acid in vivo
- SE: GI most common, often causes a rash (limits use)
- CI: PREGNANCY!!! women of child bearing age must use contraception
- Uses: combined with cyclosporine/tacrolimus and glucocorticoids to prevent rejection.
7
Q
Azathiprine
A
- MOA: converted to 6-mercaptopurine in vivo, inhibits de novo purine synthesis, blocks transcription and cell proliferation. Many lymphocyte actions inhibited, inhibits delayed hypersensitivity and cellular cytotoxicity after transplant.
- Kinetics: metabolized by xanthine oxidase
- SE: Bone marrow suppression, inc infections (esp herpes), N/V/D, liver toxicity (elevated enzymes), teratogenic, alopecia, skin rashes
- Uses: Used as adjunct with tacrolimus/cyclosporine and prednisone to prevent transplant rejection, tx glomerulonephritis of SLE, severe RA
- CI: Pregnancy, must reduce dose greatly if pt is on allopurinol (xanthine oxidase inhibitor).
8
Q
Leflonimide
A
- MOA: Inhibits dihydroorotate dehydrogenase –> dec de novo pyrimidine synthesis –> decreased lymphocyte activation
- SE: Liver and renal toxicity, teratogenic
- CI: pregnancy
- Uses: RA
9
Q
Cyclophosphamide
A
- MOA: direct effect on T and B lymphocytes, especially those which have undergone antigenic differentiation and division.
- Kinetics: CYP450 activation
- SE: Hemorrhagic cystitis (prevent w/ hydration and MESNA), N/V, BM suppression, bladder fibrosis and carcinoma, alopecia, teratogenic
- CI: Pregnancy
- Uses: Organ transplant (can inhibit established immune response, good for rescue). Severe MS, RA, SLE. BM transplants, anti-neoplastic.
10
Q
Prednisone
A
- Steroid, used for general immunosuppression
- depress macrophage response, lysis of lymphocytes, decreases cytokine production and responses, inhibits T-cell proliferation, anti-inflammatory
- SE: Cushings syndrome, immunosuppression, osteoporosis, suppress HPA axis
- Uses: minimize allergic responses to anti-lymphocytic globulin/monoclonal ab. Transplants both to prevent and treat acute rejection, immunosuppressive for all allergies
11
Q
Methotrexate
A
- MOA: inhibits dihydrofolate reductase inhibitor –> T-cell and macrophage inhibition (inhibits folate-dependent steps in purine syn).
- Kinetics: well absorbed orally, renal excreted.
- SE: BM suppression, alopecia, hepatotoxicity, teratogenic
- CI: Pregnancy
- Uses: immunosuppression in organ transplants, psoriasis, RA
12
Q
Thalidomide
A
- MOA: Decreases TNF-alpha and IL-6 –> shifts T-cell response to TH2 subset, decreases activity of neutrophils, enhances cell mediated immunity by T cells
- Kinetics: Oral admin
- SE: TERATOGENIC!!!!!!!, inc risk of DVT, sedation, neutropenia
- CI: PREGNANCY!!!!!
- Uses: Prevents graft v host, acute myelogenous leukemia. Tx of multiple myeloma, leprosy, some cancers and causes weight gain in AIDS wasting.