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22 Cards in this Set
- Front
- Back
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Biological agents used for Chronic Hep B infection |
Interferon alpha-2b PEG-Interferon alpha-2b PEGylated Interferon alpha-2a |
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Nucleoside reverse transcripatse inhibitors for chronic Hep B infection |
Adefovir (Adenosine) Entecavir (Guanosine) Telbivudine (Thymidine) Tenofovir (Adenosine also for HIV) Lamivudine (Cytosine also for HIV) |
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What is the goal of drugs for chronic hep B infections |
Slow development of liver disease
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Pregnant women and hep B |
All pregnant women need to be tested for HBV infection.
If they are positive immediately after delivery the baby needs to have HBV vaccination and be given hepatitis B immune globin. |
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Clinical indication for Interferon-alpha drugs |
They are primarily used for the treatment of patients with well compensated liver disease and who do not wish to be on long term treatment or who are planning to be pregnant within the next two to three years. |
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Interferon vs PEG-interferon pharmacokinetics |
Interferon 3 x weekly because it peaks then drops within 24hrs.
PEG will stay in blood and last for a week |
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Interferon alpha or PEG interferon alpha treatment of chronic HBV pros |
shorter course good efficacy decreases HBV DNA decreases HBeAg Acquired resistance rare
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Cons of interferon alpha or PEG interferon alpha treatment of chronic HBV |
Parenteral Expensive Side effects create flu like syndrome with depression.
DANGEROUS IN DECOMPENSATED CIRRHOSIS |
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Interferon alpha MOA |
IFN receptor activates JAK1 and TYK2 which then phosphorylate INF receptor. Stats are recruited and JAK1 and TYK 2 phosphorylate STATs and they dimerize and go to nucleus. ISGF2: DNA complex up regulates transcription of interferon stimulated genes. The genes encode proteins which cause antiviral and immunomodulatory mechanisms. (Degrading viral protein and inhibiting protein synthesis) |
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How does immunomodulation of interferon alpha work? |
It favors Th-1 cell immunity which eradicates HBV… but also causes inflammation and fibrosis.
Hepatitis flare is a sign that seroconversion is progressing and antibodies to HBV Ag are being made. |
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Contraindication of Interferon alpha or PEG interferon alpha |
Dangerous with decompensated cirrhosis.
Patients with one or more complications of chronic liver disease, such as ascites, encephalopathy, variceal bleeding, coagulopathy, and hepatocellular carcinoma. |
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Does limiting toxicity for interferon alpha or PEG interferon alpha |
bone marrow suppression Neurotoxicity (behavioral changes) |
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Clinical indications for Nucleoside (tide) analog viral reverse transcriptase inhibitors. |
Chronic, suppressive, or oral single agent treatment.
better tolerated than interferons but not usually curative. CAN be used in patients with compensated or decompensated cirrhosis. |
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Oral drugs for chronic HBV |
Entecavir (G) Adefovir and Tenofovir (A) and nucleotide monophosphates. Lamivudine (C) Telbivudine (T)
They need to be activated by cell kinases into nucleotide triphosphates |
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MOA of NRTI's |
They terminate viral DNA synthesis because they lack 3' hydroxyl group. so additional nucleotides cannot be added.
The can also terminate HBV replication and Viral DNA polymerase |
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HBV Resistance To Nucleosides -What causes it -what can be given instead |
Impaired purine/pyrimidine kinase activity Mutation of DNA polymerase
Nucelotide analogs like adefovir and tenofovir can be given because resistance involves impaired purine/pyrimidine kinase activity and slow/low conversion of nucleosides into a nucleotide monophosphate form. |
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How to handle breakthrough infection from antiviral drug resistance Resistance to lamivudine/telbivudine resistance to entecavir Resistance to adefovir |
Rescue antiviral therapy must be done
For lamivudine/telbivudine resistance add adefovir to treatment or switch to tenofovir.
If entecavir resistance then add tenofovir
For adefovir resistance add lamivudine, telbivudine, or entecavir. |
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Anti-Viral Nucleoside for treatment of chronic HBV |
It has a poor resistance profile.
but it is useful in HIV co-infection pregnancy category |
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First-line oral anti-HBV agents 2nd line oral anti-HBV agents |
First line: Tenofovir, Entecavir, Adefovir
Second line: Lamivudine, telbivudine |
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What are the limitations of lamivudine, telbivudine, and adefovir after 1 year of therapy |
Lamivudine has the highest risk for drug resistance. (mutant HBV polymerase) adefovir: has poor HBV, DNA elimination and HBeAg seroconverstion Tebivudine has a high risk for drug resistance. (same as lamivudine) |
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Which drug is the best after 1 year therapy |
Tenofovir : its first line treatment as well as additional treatment for patients with lamivudine, telbivudine, or entecavir resistance. |
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Entecavir -why is it superior -does resistance occur? -does it cause renal impairment? |
potent antiviral activity and low rate of drug resistance.
If patient has lamivudine resistance they are more likely to have entecavir resistance.
no renal impairment. |
