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antivirals part 2

Which drugs are approved for infleunza? Amantadine, Rimantidine, Oseltamivir, Zanamivir
what is the significance of segmented genome? most likely cause of mutations as they are always sharing genomes with each fragments
what 2 proteins are on Influenz virus? Hemaglutinin and Neurominidase
describe the outer and inner structures of influenza singe stranded RNA genome with segmented genome, protein capsid and protein shell enveloped virus. lipid bilayer with hemagluttinin and neurominidase. also brings its own polymerase
whats the point of hemaglutinin? use for attaching to respiratory cells
what is neurominidse used for? used for budding
which drugs prevent influenza viral uncoating? Amantadine and Rimantadine
how does amantadinea nd ramantadine work? they block ion channels and influx of proteins which prevent uncoating
which drugs prevent influenza virus from budding? Zanamivir Oseltamivir
what 2 targets do inlfueza drugs target? Uncoating and budding
what is the downfall of amantidine and rimantidine? its only work for type A influenz and resisitence
why was rimantadine drug made? 4-10x more active used mantadine and modified it
describethe half life of drugs used for uncoating influenza? long half life
what are some adverse effects of amantadine? CNS effects. interferes with dopamine you may see behavioral changes, delirium, hallucinations
why are we geting CNS side effects with amantidine? lipophilic so it penetrated the brain well
whchi drugs are used for both inlfuenza and parkinson? amantadine
what is the advantage of the newer antiinfluenza dugs? against type a and type b. zanamivir and oseltamivir
what is the mainstay drugs for influena? Zanamivir (relenza) Oseltamivir (tamiflu)
How does zanamivir adn oseltamivir work? neurominidase inhibitors. blocks it from cutting the sialic acid
what is sialic acid? 2 strands used as it buds from the host cell. it attaches to host cell membrane and neurominidase comes and clips the sialic acid
how doe sneurominidase work? clips sialic acid to allow virus to leave the cell
how is zanamivir used? inhalation has poor bioavailability
side effects of zanamivir? nose and throat discomfort broncho spsms
how should oseltamivir be given? give with food because can cause nausea and vomiting
how are influenza ciruses resistnat to drigs? many strains are already resistant to amantadine and rimantidine, resistance to oseltamivir is from mutation of viral neuraminidase
how has resistane to oseltamavir developed? mutation in virla neuraminidase
transmission of hepatitis A fecal-oral, parenteral sexual
transmission of hepatitis b parenteral, sexual
transmission of hepatitis c parenteral
transmission of hepatitis d parenteral, fecal-oral, sexual
transmission of hepatitis e fecal-oral
which hepatitis can cause chronic infections B,C,D
how to prevent and treat Hepatitis a hygene, HAV
how to prevent and treat Hepatitis b heigene, HBV
how to prevent and treat Hepatitis c hygene, screen blood, interferon alpha and ribavirin
how to prevent and treat Hepatitis d heigene HBV
how to prevent and treat Hepatitis e hygiene save water
whats the significance of long incubation period? asymptomatic, you dont know you have it, highest chance of transmission
if hepatitis is transmitted fecal oral how can they be transmitted? bad hygiene, bad water supply, eating shellfish
which hepatitis do we not have vaccines against? Hepatitis C and E
what is unique about hepatitis b and c ? both blood born and hae potential for long term effects of liver
what can put u at an increased risk for liver cancer? chronic hepatitis B it is an oncogenic virus - not so much with hepatitis C
wht is an oncogenic virus? hepatitis B. has potnetial to change cells into cancerous cells
which drugs treat hepatitis B? Lamivudine, entecavir, telbivudine, adefovir, tenofovir, interferon alpha
which drugs treat hepatitis c Interferon, ribavirin, protease inhibitors
the drugs that treat hepatitis B does what? inhibit HBV DNA polymerase they are falsoe nucleosides
what is different about the treatment for heaptiis C? hepatitis C is an RNA virus so the drugs used to treat Hep B inhibit DN A polymerase
is there a cure for hepatitis B? hepatitis c? no treatment is supressive for hep B, Hep C is potentially curative
which drugs are high potency in HBV>? Tenofovir and entecavir because after a few years there is still veryy low resisitence
greates drawback of lamuvidine for HBV high resistance - 70% at 5 years, 10-30% at 1 yr
which drugs for HBV have high resisitence Telbivudine, adefovir
which rug is structurally similar to tenofovir? adefovir- it is the diester pordrug
what does it mean if a drug is a low barrier to resistance? ow much mutation is needed to make an orgnaims resistant to drug> if it is low than it doesnt take much mutations to cause resistnace
which drugs have a low barrier to resistance for hbv? lamivudine
which drug has a high barrier to resistnece? entecavir and tenofovir
which drugs have intermediate barrier to resisitance? adefovir, telbivudine
what is mainstay for hepatitis B and C? interferon
wha are interferons? endogenous, we make this to fightoff interferons, binding of interferons to cells initiate a number of antiviral proteins
what do our cells make to fight viral infections? interferons
what happens when you get interferons at low doses when the body makes it is is very good antiviral but when we hike it up and pharmacological levels it can cause tremendous ammounts of side effects and toxicities
how do interferons work endogenously? inhibits transcription, inhibits translation, inhibits post translational processng, inhibits virus maturation, inhibits viral release
how are interferon alpha given? SC or IM for HBV and HCV
what is the point of pegylating interferons? we add polyethylene glycol chains to it to increase bioavailability, better tolerated, reduces clearance increases half life sothis reduces dosing
what are side effects of interferon? flulike symptoms, thrombocytopenia, granulocytosis, elvated serum aminotransferase levels, fatigeu nause headaceh anorexia rahs, severe psyciatric side effects - depression, psycosis
contraindications of interferon psycosis, depression, seizure, severe cirhosis, underlying blood liver and cns issues, not given during pregnancy
What is ribavirin? broad spectrum inhibits influenza, hcv, hiv, rsv...lots of viruses
how does ribavirin work? inhibits viral GTP syntheisis, mRNA procesing and RNA polymerase
what is ribavirin currently approved for? combination therapy with interferon for HCV, aerosolized for severe RSV infections
side effects of ribavirin? fatigue, headache, insomnia
oregnancy category of ribavirin? Category X
what is th epurpose of protase? it modifies proteins to make viruses funcitonal
what are HCV protease inhibitors? Telaprevir and Boceprevir
drug treatment for HCV? Telaprevir and Boceprevir
how does telaprevir and boceprevir work HCV protease inhibitro to make immature non fucntiona viruses
which drugs are used as a tripple therapy Pegylated interferon, ribaviron and protease inhibitor for Hep C
what is benefit of triple therapy sustained virologic response to HCV increased to 70-80%
adverse effect of hcv proteae inhibitors? fatigue nausea anemia but generally tolerbale
describe structure of HIV blood born, obligate parasite, duble stranded identicle RNA virus, retorvirus, envelope, ipid bilayer comes from host cell when buds, uses cd4 cells
what is a retrovirus? from RNA to DNA when it replicated
gp120 and gp41 glycoprteins on surface of HIV peplomers/ spike
what are 2 imporatnat glycoproteins on the surface of hiv cells? gp120 and gp41
cd4 cells are aka what? helper t cells
what part of hiv binds to cd4? gp120
what does reverse transcriptase do? comes with HIV cell to make DNA from RNA
what does HIV integrase do? integrates into host cell genome
what does HIV protease do?
where do hiv cells bind? to CD4 membranes and chemokine receptors on host cells
what are the targets of antiretroviral drugs? inhibit HIV reverse transcriptase, protease inhibitors, fusion inhibitors, integrase inhibitors
what drugs inhibit reverse transcriptase? Nucleoside/nucleotide analogs (NRTI) and nonnucleoside analog (NNRTI)
what is a helathy cd4 cell count? greater than 1200
how is effectiveness of hiv therapy judged by cd4 cell count, plasma hiv RNA levels ( usually undetective because hiv hae their genome in their cells)
at what point does someone become at risk for opportunistic infections? below 500
when is hiv therapy usually started? when cd4 cell count drops to 350?? subjective
quiescent HIV DNA can remain in infected t cells
what are goals of HIV therapy? preserve immune system prevent resistence, preserve future treatment options***, select terapy pt will tolerate, minimize short term adn long term effect
what is the most important gola of HV therapy? preserve furutre treatmetn options
what is the mechanisms of NRTI and NNRTI? mimic endogenous nucleosides
what happens when yu give an NRTI or NNRTI? chain termination
what was a big issue with early NRTI? short half life, toomany dosages
why are new agents of NRTI better? longer half life, ease compliance
where are NRTIs primarily eliminated? Renal
what is black box warning with an NRTI drug? abacavir causes fatal hypersensitivity
how are organisms resistant to NRtIs? mutation in reverse transcriptase impairing the ability of RT to incorportate the drug into DNA, removal of analog from DNA by ATP or pyrophosphate
what are NNRTI? they are not nucleosides but they still inhibit reverse transcriptase
what is an allosteric inhibition? noncompetitive inhibiton, binds somewhere else and changes the structure
which drugs are NRTI? Tenofovir, AZT (Zidovudine), Lamivudine, Stavudine, Abacivir,
which drugs are NNRTIs? Nevirapine (NVP) Delvirdine (DLV, Efavirinz EFV Etravirine ETR, Rilpivirise RPV
pros of NNRTI? long half life and great bioavailability
How are NNRTIs eliminated? Liver. cyps
what are major side effects of NNRTIs? skin reaction, serious skin reaction with NVP, rahss and hypersensitivity reaction
what are some key interactions with NNRTI? CYP3a4 interactions so interactions with other drugs that inhibit or are metabolized by CYP3A4
what are the resistance of NNRTIs? mutation to hydrophobic core
where do NNRTIs bind? hydrophobic core on RT
what is the pro of mutations for NNRTIs? tend to be drug specific and many drugs bnd to different parts of RT drug specific mutations. unliek NRT
what do Protease inhibitors do? inhibit HIV enzyme that are needed for maturation of HIV different target. acts on protease enzyme
examples of protease inhibitors Saquinavir, Ritonavir, Indinavir
how are protease inhibitors emtaboized? Cyps
what is one thing to remember when givien protease inhibitors? has effects with meals. bioavailability is dependant on high fat meals
what are some interactions of protease inhibitros? they inhibit CYP34a severe hepatic impairment
kaletra Lopinavir/Ritanovir
what is the boosting effect of Kaletra? ritinovir inhibits metabolizms if lopinavir makign more drugs available boositng its effect
what is RItonavir given? not for its antiviral effect but for its boosting effect it inhibits CYP3a4
side effects of protease inhibitor? buffalo hump, dyslipidema, hyperglycemia, lipodystrophy with exception of aazanavir
how are organisms resistnat to protease inhibitors? resistance can develop quikly so you never use it alone. they all bind to the same place allways. so cross ressitnce is high
describe HIV protease its a homodimer with a central drug inding core. mutations reduce affinity of amino acid binding region
which drugs are fusion inhibitors Enfurvitide, maraviroc
what is enfuvirtide? class of fusion inhibitor peptde ( must be given parenteral) interferes with gp41 prevents it from changing shpe and fusing together. so i alows attachment but doesnt allow fusion
what does gp41 do? imbeds into cd4 cells and anchors to it. than it flattens out and changes shape and pulls membrane of cd4 cell together fusing them together and forming a pore
how is efuvirtide given? s.c its a peptide. fusion inhibitor
how is ecfuvirtide metabolized? NO CYPS!!! proteolysis metabolusm
side effects if Enfuvirtide injection site reaction, hypersensitivity, eosinophilia no major interactiosn htough
how are orgnaisms resistant to enfuvirtide? mutation of HIV gp41
how does maraviroc work? binds to CCR5 chemockine receptor. if hiv doesnt bind to chemockime and cd4 membrane than there is poor fusion
why is maraviroc approved for? pts who have treatment failure to other HIV drugs
what is the significance of mutated ccr5? its a chemockine receptors and some long term non progressive pts have a mutated ccr5 sorta like beign immune to HIV virus cuz now it cant bind
what is CXCR4 another chemokine recptors used to bind HIV. some HI use CCR5 and some use CXCR4
whats the problem with maraviron? only works with CCR5, but if hiv works on CXCR4 it wont work. so you have to test to see where the hiv is working against. also we need CCR5 for normal immune survalience, so is our immune system going to be effected because of this?
adverse effects of maraviroc? hepatotoxicity, blocks ccr5 so it can effect immune survelliece
does maraviroc use cyps? yes cyp3A4
how are mutations to maraviroc made? mutations in HIV gp120, emergence of CXCR-4 tropic virus
which drug is an integrase inhibitor? reltegravir
how does reltegravir work? integrase inhibitor that binds to HIV integrase prevents integration of reverse transcriptase viral DNA into host gene. allow infection fusion uncoating, copying but doesnt allow double stranded DNA to be encorp into host cell
benefit of raltegravir? no CYPS so less adverse effects with other drugs
what is the downfall of Raltegravir? one single point mutation can cause significant resistnace so low genetic barrier to resistnace but non so far
adverse effect of raltegravir? increase CK so potential for myopathy, insomnia headahce NVD
what is so importnat of about the first attempt to control viral replication? most important because th pt gains most benefit from monimizing viral replicaiton and maximizinf immune funciton. this is as strong as your immune systems is ever gnna be in the begining
what is HAART? Highly active anti retroviral therapy, combination of anit HIV drugs to bring HIV levels down to below detectabe. multiple drugs is great way of overcoming resistance
what are the current reccomedaions for HAART? 2 NRTI PLUS 1 NNRTI OR Ritonavir boosted PI (atazanovir, darunavir) OR Integrase inhibitor (raltegravir)
what is Atripla Efavirenz, Emtricitabine, Tenofovir
what do protease inhibitors end in? -avir
what is a fusion inhibitor drug enfuritide
which drug is a ccr5 inhibitor? maraviroc
which drug is an integrase inhibitor Raltegravir
which popular drugs are NRTI? AZT (zidovudine), didanosine, tenofovir, staVUDINE, lamiVUDINE, abacavir
which drugs are NNRTI? delavindine, efavirnze,
Created by: Cherry5301