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27 Cards in this Set
- Front
- Back
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Thymoglobulin
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- polyclonal antibody against T cell markers
- Ig obtained by immunization of rabbits with human thymocytes - use for: prevention of acute rejection, treatment of rejection, treatment of graft vs. host in BMT, treatment of severe aplastic anemia - adverse effects: cytokine release syndrome, antibodies against the antibodies, chills/fever, leukopenia, thrombocytopenia, skin rashes |
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Muromonab-CD3 (OKT3; Orthoclone)
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- murine monoclonal antibody against CD3 --> blockage of TCR (initial binding to CD3 causes cytokine release)
- IV administration; excreted mostly in bile - adverse effects: cytokine release syndrome, fever, pulmonary edema, CNS effects, infection (CMV) --> rarely used today |
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Basiliximab (Simulect)
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- murine-human chimeric monoclonal antibody that binds the IL-2 receptor (CD25) on activated T cells
- higher affinity but shorter half-life than daclizumab - used to prevent rejection - adverse effects: primarily GI but also anaphylactic reaction, lymphoproliferative disorders, infection |
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Daclizumab (Zenapax)
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- humanized monoclonal antibody with high affinity for the IL-2 receptor (CD25) on activated T cells
- lower affinity but longer half-life than basiliximab - used to prevent rejection - adverse effects: primarily GI but also anaphylactic reaction, lymphoproliferative disorders, infection |
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Cyclosporine (Sandimmune, Neoral)
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- calcineurin inhibitor: enters T cell and forms complex that binds to calcineurin, leading to decreased IL-2 production
- used to prevent/treat rejection, graft vs. host, autoimmune disease - given with glucocorticoids - mostly oral but sometimes IV administration; metabolized by CYP3A4; excreted mostly in bile - adverse effects (dose-dependent): *nephrotoxicity, hepatotoxicity, infection, lymphoma, anaphylactic reaction, hypertension, hyperkalemia, tremor, hirsutism, glucose intolerance, gum hyperplasia |
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Tacrolimus (Prograf)
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- calcineurin inhibitor: similar mechanism to cyclosporine (forms complex with FKBPs and binds calcineurin in T cell --> decreased IL-2)
- 10-100X more potent than cyclosporine, and more toxic - used to prevent rejection - oral administration preferred - metabolized like cyclosporine --> similar side effects (hypertension, nephrotoxicity, hyperglycemia, tremor); does not cause hirsutism or gum hyperplasia |
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Azathioprine (Imuran)
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- impedes de novo synthesis of purines required for lymphocytic cell division
- adverse effects: bone marrow suppression (--> leukopenia) |
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Mycophenolate mofetil (CellCept)
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- most common of the antimetabolites used to prevent rejection
- hydrolyzed in the GI tract to mycophenolic acid --> rapid absorption - reversible, noncompetitive inhibitor that blocks the de novo formation of GMP (required for lymphocyte proliferation) - used in combination with cyclosporine and corticosteroids - excreted predominantly in urine - adverse effects: pain, diarrhea, leukopenia, sepsis, lymphoma |
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Mycophenolic acid (Myfortic)
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- same as mycophenolate mofetil (which gets hydrolyzed in GI tract to mycophenolic acid)
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Sirolimus (Rapamune)
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- binds to mTOR --> inhibits T cell proliferation in response to IL-2
- used to prevent rejection in combination with cyclosporine and corticosteroids; not as potent as calcineurin inhibitors - metabolized by CYP3A4 - adverse effects: hyperlipidemia, thrombocytopenia, leukopenia, poor wound healing |
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Glucocorticoids
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- methylprednisolone, prednisone: broad effects on cell-mediated immunity (cause rapid decrease in blood lymphocyte levels, down-regulate cytokine release, inhibit lymphocyte proliferation and activation)
- used to treat acute rejection, autoimmune disorders, and graft vs. hose disease in BMT - side effects: growth retardation, avascular necrosis of bone, osteopenia, infection, poor wound healing, cataracts, hyperglycemia, hypertension |
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Chlorpheniramine (Chlortrimeton)
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- H1 antagonist
- CNS side effects more common, sedation less common |
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Cetirizine (Zyrtec)
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- 2nd generation H1 antagonist (but still causes some sedation)
- minimal anti-cholinergic effects - excreted primarily in urine |
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Cyclizine (Marezine)
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- used to counter motion sickness (but promethazine is more effective)
- similar to meclizine |
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Desloratadine (Clarinex)
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- 2nd generation H1 antagonist
- metabolite of loratadine |
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Dimenhydrinate (Dramamine)
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- metabolized to active form (= diphenhydramine)
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Diphenhydramine (Benadryl)
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- H1 antagonist with significant anti-muscarinic activity
- = the active moiety of dimenhydrinate - --> sedation - also used to treat motion sickness |
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Fexofenadine (Allegra)
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- 2nd generation H1 antagonist
- used to treat allergic rhinitis - oral administration; rapid absorption |
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Loratadine (Claritin)
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- 2nd generation H1 antagonist
- active metabolite (desloratadine) generated in liver by CYP metabolism - excreted primarily in urine |
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Meclizine (Antivert, Bonine)
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- used to counter motion sickness (but promethazine is more effective)
- similar to cyclizine |
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Promethazine (Phenergan)
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- H1 antagonist
- strong anti-muscarinic activity - uses: anti-emetic, local anesthetic, motion sickness - --> sedation |
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CYP3A4 inducers/inhibitors
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- inducers: anticonvulsants, clindamycin, rifampin, St. Johns wort
- inhibitors: azole antifungals, antiretroviral agents, Ca channel blockers, cimetidine, carvedilol, grapefruit juice, warfarin, etc. - inhibitors will cause increased concentrations of drugs metabolized by CYP3A4 (like cyclosporine and tacrolimus) |
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H1 receptors
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- GPCR targeted by anti-histaminic drugs
- coupled to phospholipase C; histamine binding causes formation of IP3 --> intracellular Ca rises --> protein kinase C activation - cause effects leading to vasodilation, increased capillary permeability, bronchoconstriction, increased airway mucus secretion, increased wakefulness (hypothalamus), pain/itch |
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Cardiac effects of histamine
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- histamine acts on heart only in high concentrations
- leads to increased contractility, increased HR, increased ventricular automaticity (H2 effect), slowed AV nodal conduction (H1 effect) - may be involved in causing cardiac arrhythmias |
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Therapeutic uses of anti-histaminics
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- allergy (relieve sneezing, rhinorrhea, itching)
- allergic drug reactions - motion sickness, vertigo, sedation (1st generation drugs) - note: bronchial asthma and systemic anaphylaxis involve other mediators; must use other drugs |
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2nd generation H1 antagonists
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- lack significant anti-cholinergic and CNS effects
- include loratadine, desloratadine, fexofenadine, and cetirizine |
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1st generation H1 antagonists
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- stabilize the H1 receptor in its inactive form (= inverse agonists)
- metabolized by hepatic CYPs, which they also induce - lipophilic, and so have CNS effects - also have anti-muscarinic effects (xerostomia, urinary retention) - side effects: sedation, dizziness, incoordination, diplopia, tremors, GI effects |
