immunopharmacology Flashcards
Vaccines
active immunization with attenuated organism synthetic antigenic peptides
antisera or antibodies
passive immunization with antisera or monoclonal antibodies
immunopotentiation
enhance the immune response
BCG- attenuated strain of mycobacterium bovis
stimulates NK T cells, may cross react immunologically with tumor cell Ags, used as an adjuvant in immunotherapy of certain cancers
Levamisole- anthelmintic drug
IL1
produced by M@ in response to viruses, bacteria, Ag, inflammatory agents
Activates lymphocytes
Promotes differentiation of Ab forming cells
Endogenous pyrogen
IL2
produced by T cells, GF for T cells and promotes proliferation, enhances tumoricytic activity of lymphocytes
IFN
a-IFN and B-IFN produced by leukocytes, y-IFN produced by lymphocytes
inhibit replication of viruses, enhance phagocytosis and cytotoxicity
Tested (B-IFN = viral infection, y-IFN)
TNF
mediator of inflammation: stimulates IL1 synthesis, activates neutrophils, stimulates PGs synthesis, stimulates collagenase production, elevated in rheumatoid arthritis
Cell mediated cytotoxicity
- Macrophage (M@) processing of Ag
- presentation of Ag to T cell
- Expression of IL 1 and IL2 receptors on T cell
- Secretion of IL 1 M@
- IL promotes IL 2 release from helper T cells
- IL2 acts on lymphocytes to promote replication of cytotoxic cells
uses of immunosuppressants
prvention of allograft rejection
treatment of autoimmune diseases
prednisolone
cell trafic accumulation: reduce access of cells to target tissue (lymphocytopenia and monocytopenia), prevects neutrophil adherence to endothelium, inhibit action of chemotactic factors
cell function: interferes with M@ Ag processing, blocks the action of lymphokines, inhibits binding to Fc receptors
used in combo with other drugs in Auto immune diesease dnd to prevent graft rejection
toxicity: supression of HPA axis, acute adrenal insufficiency with abrupt withdrawal, Cushings syndrome
Contraindicated in presense of exisiting infection
cytotoxic agents
in response to antigen, immune cells proliferate in a synchronized manner with a burst of mitotic division. These drugs kill these rapidly proliferating cells
best used at time of intial exposure to exposure, kills a high precentage of precursor cells
Relevant clone stimulated by Ag will be killed. other immune cells and clones not stimulated by Ag are spared
usually administered in a low dosage daily to block immunoproliferation continually
Azathioprine
Metabolized to 6 Mercaptopurine, orally active, purine anti metabolite that inhibits purine biosynthesis and thereby inhibits DNA synthesis (de novo and salvage paths)
inhibits rejection of transplanted organs and in some diseases as rheumatoid arthritis
bonemarrow depression is a major side effect, GI and hepatic toxicity may occur
Cyclophosphamide
an alkylating agent that results in agent that results cross linking of DNA to kill replicating and non replicating cells
Toxic effect more pronounced on B cells so more effective in suppressing humoral immunity
Orally active
used in the treatment of autimmune diseases not effective in preventing graft rejections
bone marrow depression as a SE
Methotrexate
inhibitor of dihydrofolate reductase- inhibit folate dependent steps in purine synthesis- inhibits DNA synthesis
Used to treat autoimmune disease, hepatic toxicity
Mycophenolate Mofetil
Metabolized to the active mycophenolic acid
MOA: lymphocyte selective immunosuppressant:
1. inhibits IMP dehydrogenase (IMP->GMP) necessary for de novo purine synthesis, no effect on salvage pathway
2. lymphocytes cant make GMP via slavage pathway, must use denovo so selective for lymphocytes
3. inhibits lymphocyte proliferation and expression of cell surface adhesion molecules
4. more selective than azathioprine and methotrexate but equally effective
Orally active
used w/ cyclosporine and corticosteroids to prevent renal allograft rejection. allows for lower dose of cyclosporine to be used so less toxicity
used to treat autoimmune diseases–rheumatoid arthritis and refractory psoriasis
should be used with caution in pts with active GI disease, reduced renal function and infections
SE: infection, leukopenia, anemia
contraind: in pregnancy (malformation and spon abortions)
Cyclosporine
lipophilic peptide antibiotic
MOA: binds to cellular receptor and inhibits Ca-dependent phosphatase. Blocks activation of transcription factor (NFAT) necessary for IL2 production
inhibits mRNA synthesis that codes for lymphokines as IL2. By blocking IL2 synthesis, it blocks T cell helper function so inhibits T cell proliferation and cytotoxicity. Does not alter T cell response to IL2. since it is not lymphotoxic, its more selective in its action
orally active
Used to prevent rejection , more effective than other agents with fewer SEs, and used in some auto immune diseases
Nephrotoxicicty is a major side effect, reversible with discont. hepatotoxicicty
Tracolimus
binds to FK binding protein, a cyclophilin-related protein. Same MOA as cyclosporine
Spectrum of action is the same as cyclosporine but 50-100 times more potent. less toxic
sirolimus
inhibits T cell activation and proliferation downstream of IL 2. binds FKBP-12.
no binding to calcineurin
binds to mTOR blocks G1–> s transition
Uses same for cyclosporine, coating of cardiac stents
basiliximab
MOA: Recombinant monoclonal antibodies against a-subunit of IL2 receptor
Blocks IL2 receptor- inhibits binding of IL2 to its receptor, inhibits T cell activation and proliferation
must be given IV
Prophylactically treats allograft rejection. Not used for acute rejection. used in combo with calcineurin inhibitor and corticosteroid
CX: pregnancy, breastfeeding infection and murine hypersensitivity
alemtuzumab
MOA: CD52 is a glycoprotein expressed on B- and T lymphocytes, monocytes and NK cells
drug binds to CD52 causing lympholysis via ADCC, causes B and T cell depletion
must be given IV
Used as an immuno suppressant in renal transplants. avoids high dose corticosteroids. Used to treat chronic lymphocytic leukemia and MS.
SE: neutropenia, thrombocytopenia anemia can occur
Belatacept
MOA: a fusion protein of the Fc fragment of the IgG1 and extracellular domain of CD152 found on T cells. CD 152 binds CD80 and CD84 on antigen presenting cells
Selective T cell co stimulation inhibitor. It binds to cell surface co stimulation ligands CD80 CD86 on T cells. inhibits T cell activation
Must be given IV
Used prophylactic organ rejeection of kidney. alternative to calcineurin inhibitors to reduce long term toxicity of the drugs. Used in combo with mycophenolate mofetil, corticosteroids and basiliximab
Toxicity- infusion related reactions are infrequent, typically well tolerated
