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41 Cards in this Set
- Front
- Back
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acyclovir MOA |
inhibits viral DNA synthesis by competition with deoxyGTP for viral DNA polymerase and chain termination following incorporation into viral DNA
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activation of acyclovir
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3 phosphorylation steps, first step is via virus-specified thymidine kinase, other 2 steps by host enzymes-thus concentrated only in infected cells
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acyclovir is typically used for
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HSV, VSV
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Ganciclovir is used for
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CMV
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Ganciclovir MOA
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inhibits viral DNA polymerase via competative inhibition and termination of viral DNA elongation
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most common adverse effect of ganciclovir
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myelosuppression
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Foscarnet MOA
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inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase directly without requiring activation by phosphorylation
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6 classes of antiretroviral agents
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1) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) 2) nonnucleoside reverse transcriptase inhibitors (NNRTIs) 3) protease inhibitors (Pis) 4) fusion inhibitors 5) CCR5 receptor antagonists 6) integrase inhibitors
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NRTIs MOA
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competative inhibition of HIV-1 reverse transcriptase-incorporation into growing viral DNA chain=premature chain termination
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what do NRTIs require
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intracytoplasmic activation via phosphorylation by cellular enzymes to triphosphate form
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NRTIs side effects
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mitochondrial toxicity (inhibition of mitochondrial DNA polymerase gamma); less commonly lactic acidosis with hepatic statosis; possible increase MI risk
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major clinical toxicity of didanosine (NRTI)
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dose-dependent pancreatitis
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major clinical toxicity of abacavir (NRTI)
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hypersensitivity rxn in 3-5% patients within 1st 6 weeks of therapy
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tenofovir (NRTI) and pregnancy
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significant placental passage in humansl decreased fetal growth and reduction in fetal bone porosity in monkeys
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zalcitabine (NRTI) main adverse rxn
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dose-dependent peripheral neuropathy in 10-20%; slowly reversible if treatment stopped
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most common adverse effect of aidovudine (NRTI)
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myelosuppression (macrocytic anemia 1-4% or neutropenia 2-8%)
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NNRTIs MOA
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bind directly to HIV-1 reverse transcirptase resulting in allosteric inhibition of RNA and DNA-dependent DNA polymerase; binding site near to but distinct from NRTIs
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NNRTIs side effects as a class
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varying GI intolerance and skin rash; metabolism by P450=drug-drug interactions
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delavirdine (NNRTI) and pregnancy
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teratogenic in rats-ventricular septal defects and other malformations
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nevairapine (NNRTI) common use
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prevention of transmission from mother to newborn when administered at onset of labor and followed by dose to neonate within 3 days
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protease inhibitors (Pis) MOA
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prevent post-translational cleavage of Gag-Pol polyprotein and prevent processing of viral proteins into functional conformations=immateure, noninfectious viral particles
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Adverse effects of Pis
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syndrome of redistribution and accumulation of body fat (central obesity, dorsocervical fat, peripheral and facial wasting, breast enlargement, cushingoid appearance); increase in LDL and triglyceride levels, hyperglycemia and insulin resistance, inducers of CYPs
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Darunavir (PI) is a concern with what allergy
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contains sulfonamide moiety and should be used cautiously in ppl with sulfonamide allergy (also true of amprenavir)
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enfuvirtide MOA
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fusion inhibitor; binds g41 subunit of viral envelope glycoprotein preventing conformational changes required for fusion
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Maraviroc MOA
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binds specifically and selectively to CCR5
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Raltegravir
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integrase inhibitor; inhibits strand transfer-3rd and 5th step of provirus integration, thus interferes with integration of reverse-transcribed HIV DNA into chromosomes of host cells
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interferon alfa MOA
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induction of intracellular signals following binding to specific cell membrane receptors-results in inhibition of viral penetration, translation, transcription, protein processing, maturation, and release, increased expression of MHC antigens, enhanced phagocytic activity of macrophages, augmentation and survival of CTLs
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typical adverse effects of interferon alfa
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flu-like syndrome wihtin 6 hours in >30% during 1st week; transient hepatic enzyme elevation in first 8-12 weeks; neurotoxicities, myelosuppression, fatigue, weight loss, rash, cough, myalgia, alopecia, tinnitus, reversible hearing loss, retinopathy, pneumonitis, possible cardiotoxicity
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contraindications to interferon alfa therapy
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hepatic decompensation, autoimmune disease, history of cardiac arrhythmia, pregnancy
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adefovir dipivoxil (NRTI) is used in
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HBV infections
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goal of treating HBV vs HCV
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HBV=suppression; HCV=eradication
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ribavirin
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used in HCV; MOA not fully known-inhibits viral RNA-dependent polymerase of certain viruses
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adverse rxns with ribavirin
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dose dependent hemolytic anemia 10-20%
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contraindications to ribavirin therapy
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uncorrected anemia, end-stage renal failure, ischemic vascular disease, pregnancy
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amantadine and rimantadine MOA
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tricyclic amines that block M2 proton ion channel of cirus particle and inhibit uncoating of viral RNA within infected host cells-preventing replication
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amantadine and rimantadine are active against
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influenza A only
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amantadine and rimantadine adverse effects
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GI and CNS (alteration of dopamine neurotransmission)-diminishes after 1st week of use; birth defects
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oseltamivir and zanamivir MOA
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neuraminidase inhibitors-interfere with release of progeny influenza virus from infected new host cells-halt spread in respiratory tract
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other uses of ribaviron
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severe RSV bronchiolitis or pneumonia
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palivizumab
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humanized monoclonal antibody directed against epitope in A antigen site on F surface protein of RSV
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imiquimod
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immune response modifier-effective in treatment of external/internal genital/perianal warts
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