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36 Cards in this Set
- Front
- Back
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What drugs can be used for HBV and HIV?
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Tenofovir and Lamuvidine
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Pregnant women
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All need to be tested for HBV infection. If positive, infant given immediate HBV immune globulin and vaccination following delivery
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Who are PEG-interferons used for?
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well compensated liver dz, do not wish wish to be on long term tx, planning pregnancy
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Pharmacokinetics of Interferon vs PEG-interferon
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Interferon 3x/week. PEG-interferon ~1/ week
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How many mechanisms for interferon/PEG-interferon alpha?
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2
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when are interferon/PEG interferon alpha contraindicated?
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decompensated cirrhosis
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mechanism of interferon alpha
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receptor activates JAK/Tyk, Jak/tyk phosphorylate IFN receptor, phosphorylated receptor recruits STAT, jak/tyk phosphorylate STAT, phospho-STAT undocks, dimerizes, and relocates to the nucleus where it upregulates antiviral/cytostatic genes
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2'5' OAS
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interferon stimulated gene. Becomes 2'5'-AAA, activates ribonuclease L, then DEGRADES VIRAL RNA
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PKR
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interferon stimulated gene. Becomes phospho-eIF then INHIBITS PROTEIN SYNTHESIS
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interferon alpha effects
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favors cell mediated T1. causes inflammatoin & fibrosis. 2 phases: inhibition of HBV replication & immune clearance of infected cells (liver damage during this phase).
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What limits the dose of interferon alpha?
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bone marrow suppression, neurotoxicity
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nucleos(t)ides vs interferon
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nucleosides are better for chronic. drugs are better tolerated. can be used in compensated or decompensated. However it is not curative.
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moa of nucleos(t)ides
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inhibit viral reverse transcriptase/dna polymerase. they lower serum HBV DNA
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NRTI
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prodrugs (nucleosides) that converted to nucleotide triphosphates (active). NRTI triphosphate terminates strand elongation because they lack a 3'-OH group (they have a 3' sulfur group instead).
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nucleoside monophosphates (nucleoTide analogs)
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Adefovir and Tenofovir. These bypass the initial kinase which is a source of resistance.
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What are the resistance mechanisms of HBV to nucleos(t)ides?
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impaired purine/pyrimidine kinase activity. mutation of DNA polymerase.
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Wildtype of DNA polymerase? (the one that HBV has when drugs are non-resistant)
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YMDD
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for lamivudine/telbivudine resistance
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add adefovir or switch to tenofovir
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for entecavir resistance
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add tenofovir
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for adefovir resistance
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add lamivudine, telbivudine, or entecavir
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First Line oral anti HBV agents
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*Tenofovir and Entecavir
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Tenofovir
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best clearance of HBV DNA, lowest drug resistance, pregnancy class B. Low efficacy when also resistant to Adefovir. Nephrotoxicity at high doses.
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Which drug has the highest incidence of resistance?
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Lamivudine. Limited by YMDD > YVDD & virological breakthrough
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Adefovir
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low frequency of resistance, but weakest drug. Low efficacy when also resistant to Tenofovir.
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Telbivudine resistance occurs with...
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lamivudine and is more expensive
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Entecavir resistance occurs with...
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lamuvidine resisrtance. Entevir is best choice for renal insufficiency.
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Best drug for a patient with renal insufficiency
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Entecavir
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NS3/4A Protease inhibitors
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Boceprevir and Telaprevir
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Ribavirin properties
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Guanosine (nucleoside) analog. Preg catagory X. Causes anemia and is 60x more concentrated in erythrocytes. Half for renal clearance = 1 day. 40 days for erythrocytes.
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When is monotherapy with pegylated interferon alpha recommended and when is it associated with a favorable response?
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in patients who cannot tolerate ribavirin. Favorable: HCV genotype 2 or 3, absence of cirrhosis, low pretreatment HCV RNA levels.
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Ribavirin given alone
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inefficient in chronic HCV. might help to suppress HCV specific IL-10 production.
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ribavirin mechanism
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inhibits IMP dehydrogenase (depletes nucleotide triphosphate pools, stops purine synthesis) and RNA dependent RNA polymerase. Shifts balance to Th1
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Standard for HCV treatment since 2011
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PEG-interferon plus ribavirin (24-48 weeks) plus oral protease inhibitors (teleprevir or boceprevir)
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side effects of boceprevir
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ANEMIA and dysgeusia
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side effects of telaprevir
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ANEMIA, rash, pruritus, diarrhea
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How do you treat a HCV/HBV combo infection
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treat the predominant virus
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