Immunosuppressants Flashcards
Anakinra
Kineret
Anti-inflammatory
recombinant nonglycosylated synthetic IL1 antagonist
MOA: competitive inhibitors of IL1
Use: RA
ADE: injection site rxn, icreased risk of infection
Glucocoticoids
Dexamethasone (decadron, Dexasone)
Anti-inflamatory
- Interfere with the cell cycle of activated lymphoid cells
- Act on both cell mediated (primary) and humoral effects
- Use: asthma, RA, organ transplants
- Long term toxicity and decreased response with long term exposure
- Three house and a condo the F will increase potency the Oh will decrease metabolism
Methotrexate
cytotoxic agent
Rheumatrex
-Accumulates Adenosine in the immune cells and block pyrimidine and purine synthesis.
-Reversible dihydrofolate reductase inhibitor.
-Anti. Inflammatory
-Blocks B cells division
-Oral and injection
-Use: RA, Chronns and lupus
ADE: Increase risk of infection, leukopenia, highly teratogenic, nausea fatigue, fever.
-DDI: PCNG, NSAID, Probenacid
Monitor: hepatic fct and liver enzymes
Leflunomide
Cytotoxic Agent
(Arava)
-Prodrug inhibitor of pyrimidine synthesis only
to Inhibit B cell division
-Anti-inflammatory
-Active ingredient teriflunomide when the O-N bond breaks open.
Use: RA
ADE: increased liver enzymes, renal impairment, teratogenic, IRI
Azathioprine
Cytotoxic Agent
Imuran
-Antimetabolite
-Prodrug metabolized to mercaptopurine (both are active)
-MOA: purine analog that interferes with purine metabolism required for lymphoid cell proliferation
-Use: RA, Chron’s, kidney transplant rejection prophylaxis, lupus, MS, and glomerulonephritis.
-DDI: allopurinol blocks xanthine oxidase necessary to break down AZA
ADE: leukopenia, thrombocytopenia, IRI, NVD
Cyclophosphamide
Cytotoxic Agent
Cytoxan
-MOA: destroys the proliferating Lymphoid cells to induce tolerance for solid and bone marrow transplants. DNA alkylation in resting cells.
Use: Most effective immunoosuppressant. Include Lupus, hemolytic anemia, pts with factor 13 antibodies
ADE: pancytopenia (low everything), hemmorrhagic cystitis, alopecia, NV, cardiac toxicity, electrolyte disturbances.
Metabolites:
1. Acrolein: kiddney and bladder toxic
2. Chloroacetaldehyde: nephro and neurotoxic.
3. quaternary aziridinium ion chelates DNA.
Mycophenolate mofetil
Cytotoxic Agent
Cellcept
-Semisynthetic derivative of mycophenolic acid. Prodrug that gets converted to mycophenolic.
-MMF increase bio.A.
-isolated from Penicillium glaucus
-MOA: inhibits T and B cell lymphocytes by inhibiting purine syynthesis.
-Uses: solid organ transplant for refractory rejection, reduce allograft casculophathy in heart transplant, RA, IBD, dermatologic disorders, stem cell transplant..
ADE: GI, headache, HTN, reversible myelosuppresion. neutropenia.
DDI: P450
Belimumab
B-Cell inhibitor
Benlysta
-BLyS inhibitor (BAFF lymphocyte stimulator)
MOA: B cell proliferation inhibitor to decrease antibody production
USE:: lupus
ADE: ND, hypersensitivity
Abatacept
(co stimulation of T-cell inhibitor)
(cept=fusion)
Orencia
-recombinant fusion protein
-CTLA-4 domain fused to IgG Fc region
-MOA: inactivate Tcell by binding to CD80 and CD86 so that CD28 cannot be bound and cannot stimulate Tcell to release cytokines.
Use: RA
ADE: hypersensitivity, infusion rxn, respiratory, increased malignancy.
Belanercept
Nulojix
- fusion protein
- MOA: inhibits T cell activation by binding to CD80 and CD86
- Use: Prophylaxis of kidney transplant rejection
- ADE: anemia, neutropenia, headache, peripheral edema.
Cyclosporine
Calcineurin T cell signaling inhibitor
Sandimmune Neoral
-MOA: binds to cyclophillin and inhibit calcineurin thereby inhibiting IL2 gene transcription stop t cell proliferation or cytokines
Use: alone or in combo with GC as an immunosprresent for organ transplant. Use with Methotrexate to prevent Graft vs host. RA, PS, asthma.
-Oral or IV, Eye drop for severe dry eyes or occular transplant
-Polypeptide antibiotic 11 AA
beauveria Nivea
-ADE: nephrotoxic, hyperglycemia, Liver dysfunction, HTN, altered mental state , hyperkalemia.
Tacrolimus
CAlcineurin inhibitor
Prograf
-macrolide antibiotics from Streptomyces tsukubaensis
-binds to immunophillin FK- binding protein (FK506) to inhibit calcineurin necessary to activate NFAT thereby decreasing IL2 production
-USE: prevent solid organ failure, prophylaxis with methothrexate or MMF for graft vs host . Ointment for etopic dermatitis and psioriasis
-ADE: P450 enzymes in the liver
ADE: nephrotoxiity, neurotoxicity, hyperglycemia, HTN, heperkalemia and GI effects.
Sirolimus
Rapamune/Rapamycin
-macrolide from Streptomyces hygrosopius.
MOA: mTOR inhibitor. Binds immunophilin FK506 binding protein 12. this comlex will inhibit mTOR which inhibits IL2 Tcell proliferration.
DDI: CYP450 or PGP inhibitors or inducers.
ADE: hepatotoxic, diarhea, pneumonitis, hyperTGC, suppression
USEs: alone or combo to prevent stem cell and solig organ rejection.
-Topical dermatological disorders.
Basiliximab
Simulect
-Chimeric mouse-human IgG1
-MOA: Binds to CD25 and act as IL2 antagonist
Use: PPX renal tansplant rejection
Daclizumab
Zenapax
- humanized IgG1
- Binds to alpha subunit of IL2 receptor (CD25)
- Use: kidney rejection PPX
Muromomab-CD3
-CD3 monoclonal antibody
-induce T cell death (Be back in 1 week)
-USE: reverse acute renal allograft rejection
ADE induce TNF, IFN gamma, fever, chills, myalgia, N/D, leukopenia
IVIG
intravenous immune globulin
-polyclonal human IgG prepared from pools of healthy donors no specific antigen.
-Normalize the effects on pt. immune networks
-MOA: reduce Thelper cells and increase Tregs. Fc receptor blockage
USEs: Ig defficiency, autoimmunity, HIV, Lupus, bone marrow transplant.
Tofalcitinib citrate
Xeljanz
Citrate salt
Use: RA
MOA: JAK inhibitor. inhibits signals from cytokines.
ADE: fungal, TB or fungal infections , cancer and Lymphoma. BLACK BOX
DDI: CYP3A4 inhibitors or induers (Ketoconazole). DO not combine with cyclosporine or AZAthrioprine.
Thalidomide
Thalomid
MOA: inhibit TNF alpha, increases IL10 production and enhance cell mediated immunity via cell interactions with tcells
USE: myeloma, Lupus. GVHD, and other cancers.
-ADE: Teratogenic, peripheral neuropathy,constipation, rash, fatigue, hypothyroidism, DVT.
-Metabolism: CYP2C19 metabolism to 3 different metabolites .
1. phthalimide yields 5 hydroxythalidomide and 5-6 hydroxythalidomide.
2. Glutaramide yields 5’ hydroxythalidomine
-Chemistry benzene with azole(five memered ring with N) ring that has two carbonyls.
Lenalidomide
Revlimid
-MOA: induces tumor cells apoptosis directly and indirectly by inhibiting bone marrow stromal support. Inhibit lymphocytes. (Same as Thalidomide).
-Use: multiple myeloma
ADE: VTE, pulmonay embolism, hepatotoxicity, bone marrow toxicity (neutropenia, thrombocytopenia)
-Teratogenic (pregnancy X)
-All stages of myeloma
Vaccination
- Tumor antigen presented to DC
- DC matures and injected back into human.
- DC go to LN and activate Tcells
Ipilimumab (Yervoy)
Tremelimumab
-fully human immune system monoclonol antibody to boost immune response
-inhibit CTLA4 (agonistic) so that CD8+ T cell.
ADE: GI, fever, breathing problem
Ofatumumab
Arzerra
-inhibits CD20 which prevents B cell activation
Used: B cell Lymphoma, B cell leukemia (CLL) , RA, MS.
ADE: muscle spasms. hypersensitivity, fever chills, cough.
Alemtuzumab
Campath
- Anti CD52 antibody. targets CD52 antigen presents surface mature lymphoctes
- USE: CLL, T-lymphocytes
- ADE: infusion related rxn, hypotension, rigors, fever, -SOB, bronchospasm, chills and or rash.
SelCIDs
selective cytokine inhibitory drugs PDE- 4 with potent TNF alpha activity.
