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33 Cards in this Set

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Acyclovir
Guanosine analog active against HSV and VZV; activated to form acyclovir triphosphate (competitive for DNA polymerase leading to chain termination) - resistance is due to lack of TK - all routes; renal excretion, used for mucocutaneous an genital herpes
Ganciclovir
DOC for CMV; inhibits DNA polymerase in CMV and HSV but doesnt cause chain termination; usually given IV; tx and prophylaxis of CMV retinitis; effects include neutropenia when given w/ zidovudine
Cidofovir
activated by host cell kinases and inhibits DNA poly in HSV, CMV, adeno and papillo; active against many resistant strains; effective in CMV retinitis, muco HSV and gential warts
Foscarnet
inhibits viral RNA, DNA, and HIV reverse trans. resistance due to point mutation in DNA poly gene; given IV; alternative for PaT of CMV infections and has activity against Ganciclovir resistance - inhibits hepres DNA poly in acy-resistance and may suprress AIDs herpes
Other Herpes
vidarabine - adenine analag w/ activity against HSV, CMV, VZV; use in severe HSV
Idoxuridine and trifluridine - topically in HSV-1; too toxic systemically
Fomivrsen - binds mRNA of CMV blocking early P.S.
HIV treatment approach
initiation of tx w/ 3 or more anti-retrovirals before symptoms appear; combos usually include 2 NRTIs w/ PI
what is HAART
highly active antiretroviral therapy - slows or reverses decline in CD4 cells
NRTIs
prodrugs converted by host kinases to triphosphates which competitively inhibit binding of nucleotides to dNTP binding site but also act as chain terminators
Zidovudine
oral active and distributed widely; used in HAART and valued in accidental needlesticks and proph against vertical transmission; bone marrow suppression, Azoles and protease inhibitors increase and rifampin decreases amount
Didanosine (ddI)
pancreatitis in alcoholics, oral bioaval reduced by food and chelating agents
Zalcitabine
high oral bio; dosage adjustment in renal patients,
Lamivudine (3TC)
80% bioavailable; also effective in HBV; renal insuffiency requires dosage adjustment
Stavudine (d4T)
nothing special; good oral avail
Abacavir
metabolized via alcohol dehydrogenase and glucoronosyltranferase; sever hypersensitivity reactions may occur
NRTI effects
may cause lactic acidemia and severe hepatomegaly w/ steatosis; risk factors include obesity, prolonged treatment and preexisting liver dysfunction
NNRTIs
bind to a different site on RT
Nevirapine
useful in preventing vertical transmission when givin to mothers, hypersensitivt reactions include Steven-Johnson syndrome and toxic epidermal necrolysis; CYP3A4 and increased by cimetidine and macrolides and decreased by rifampin
Delaviridine
drug interactions are major problems; skin rash in 20%; avoid in pregnancy
Efavirnez
shown effective when used w/ 2 NRTIs; frequent drug interactions; avoid in pregnancy
Tenofovir
does not require activation; causes chain termination similar to NRTIs; GI irritation most common effect
Protease Inhibitors
assembly of virions dependent on aspartate protease encoded by pol gene; all end in =Navir
Indinavir
maintain good hydration to reduce renal damage; inhibitor of CYP2A4; increases levels of antihistamines, benzodiazepines, and rifampin
Ritonavir
oral bio good, take w/ meals; Gi irritation and bitter taste
Saquinavir
take w/ food; headache and neutropenia. levels increased by azole, clarithromycin, grapefruit juice, indinavir and ritonavir; inducers of CYP3A4 decrease levles
Others
Nelfinavir - both inducer and inhibitor of P450 (diarrhea)
Amprenaivr
Lopinaivr
Protease inhibitor effects
lead to disorders of carbohydrate and lipid metabolism due to inhibition of lipid-regulation proteins - syndrome includes hyperglycemia and insulin resistant hyperlipidemia w/ altered body fat distribution
Fusion Inhibitors
Enfuviritide
binds to gp41 sub-unit on viral envelope and prevents conformational changes needed for fusion; administered subcutaneously in combo; metab does not involve P450
AntiInfluenza Agents
AMatadine and Rimatadine
inhibit early step replication of InfA but not influB virus - prevent uncoating by bindin to M2 protein which functions as proton ion channel required at onset of infection to permit acidifcation of virus core which in turn activates RNA transcriptinase - rimatidine is no greatest but its longer half-life requires no dosage adjustment in renal failure
Oselteamivir and Zanamivir
Inhibitors of neuramindase procuded by FluA and fluB - these viral enzymes cleave sialic acid residues from viral proteins and surface proteins of infected cells to function to promote virion release and to prevent clumping of newly released virons - they impede viral spread; Oseltamivir is prodrug used orally actiavted in gut and liver; Zana is admin itranasally
INF-a
cytokin that acts by activating JAKS which act to actiavted STATS to increase amount of antiviral proteins - selective action due to activation of host ribonuclease that degrades viral mRNA and also by formation of NK cells; used for chronic HBV or w/ Lamuvidine; when used w/ Ribavirin, the progression of acute HCV to chronic HCV is reduced; pegylated is superior; other uses included Kaposi sarcoma, papillomatosis, and topically for genital warts; toxic effects include GI irritation, a flu-like syndrome; neutropenia, reversible hearing loss,
Adefovir
competivitly ihibits HBV DNA polymerase and results in chain termination - good oral and unaffected by foods; suprresses HBV replication and improves liver histo and fibrosis; good for lamivudine resistant strains
Lamivudine
active in chronic HBV; longer intraceullar half-life in HBV cells and can be used in lower doses than w/ HIV treatment- supresses HBV replication and is nontoxic; If HBV DNA comes back, switch to INF-a or Adenovir
Ribavirin
inhibits replication of wide range of DNA and RNA viruses (flu, parainflu, RSV, paramyxo, HCV, HIV - mechnanism unknown; inhibits guanosine triphosphate formation, prevents capping of viral mRNA, and blocks RNA-depenedent RNA polymerasies - effective orally (Avoid antacids) and is available IV are aerosol; used adjunctively w/ INF-a in chronic HCV and in patients w/ compensated liver disease - monotherapy is not effective; early IV administration lowers mortatily in viral hemorrhagic fevers; no benefit in treatment of RSV, systemic use results in hemolytic anemia, avoid in pregnancy