Drugs for HCV and HBV Flashcards
What is the MOA of Tenofovir disoproxil
Pro-drug for tenofovir. Nucleotide analog of AMP - gets phosphorylated = diphosphate form inhibits HBV polymerase and produces chain termination
What is the MOA of Entecavir
- guanosine nucleotide analog
- triphosphate form inhibits HBV polymerase
What is the MOA of adefovir
- AMP analong
- diphosphate form incorportated into viral DNA producing chain termination
What is MOA of lamivudine and emtricitabine
L-isomer of cytosine
- triphosphate form inhibits HBV polymerase
What do you need to worry about anti-viral resistance for HBV infxns
- tends to be structure specific
- adefovir and tenofovir have acyclic phosphonate structure
- entecavir has a d-cyclopentane
What are some general characteristics for HBV anti-viral drugs?
- little or no CYP interaction
- renal function in important - dose reduction in renal dysfuntion.
- Entecavir has longest half life
How is bioavailability affected in HBV drugs?
- Tenofovir – take w/ high fat meal
- Entecavir - food delays absorption
- rest - food has no substantial effect
What are ADEs for Tenofovir
- Rental toxicity - so test creatinine and BUN, avoid concurrent usage of nephrotoxic agents like NSAIDS
- Bone pain, bone fractures, pain in extremities, muscle pain –> Osteoporosis -> give Ca and Vit D supplements
- Hepatic toxicity - lactic acidosis, steatosis. Check LFTs. This is common in W, obesity, alcoholism, prolonged drug exposure
What is thought to be the mechanism of the renal and hepatic toxicity for anti-virals
inhibits mitochondrial DNA polymerase
When you have a co-infxn of HBV and HIV, what should you give the patient?
- tenofovir, entecavir = truvada
- don’t use lamivudine and emtricitabine
ADS for adefovir, Lamivudine, entecavir
- adefovir - renal toxicity and hepatic
- Lamivudine - renal tox
- entecavir - renal and hepatic tox
What is the MOA of interferons
Antiviral, antiproliferative, and immunomodulatory.
- binds to receptor, activates TK (Jak/STAT) –> produces several IFN stimulated enzymes.
1. Endoribonucleases cleave ssRNA
2. Inibitory effects upon dsRNA
3. inhibition of viral penetration, uncoating, assemly, and release
4. enhances lytic effects of cytotoxic T cells
IFN ADEs
- Acute FLS following injection - can treat w/ antipyretics
- Dose limiting Neurophysc issues, myelosuppression w/ granulocytopenia, and thrombocytopenia. Hepatotoxic - checks LFTs.
- Monitor thyroid function and give appriopriate treatments for symptoms and continue antiviral treatment.
MOA of ribavirin
- enhanced host T cell immune clearance of HCV
- inhibit IMPDH w/ depletion of pools of GTP (essential substrate for viral RNA synthesis)
- direct inhibition of HCV replication
- RNA virus mutagenesis drives HCV to error
What effect does ribavirin have on the clinical dz of HCV
transiently reduces HCV RNA but normalizes ALT; syngerizes w/ IFN to decrease risk of viral relapse
ADE of ribavirin
Hemolytic anemia, fatal/nonfatal MI, difficulty breathing, male mediated tertaogenicity
bioavability of ribavirin
- increased w/ high fat meal
- very large Vd and long half life - extensive uptake into cells
- NO CYP action
MOA of Telaprevir and Boceprevir
NS3/4A serine protease inhibitors
Bioavailability of Telaprevir and Boceprevir
- less effective in AA
- produces benefit in naive pts and those relapsing on combo therapy
- Take w/ food ( high fat for telaprevir)
- Hepatic metabolism w/ elimination in stool
- extensively bind plasma proteins
What is the ADE of telaprevir
- fatigue, anemia, nausea
2. BBW for serious rash
ADE of Boceprevir
fatigue, anemia, nausea
Pharm characteristics for Telaprevir and Boceprevir
- Telaprevir : substrate and inhibitor for CYP3A4 and Pgp
- Boceprevir : metabolized by aldoketoreductase and CYP3A4/PgP
* co admin w/ strong CYP3A4 inducers or w/ drugs reliant on CYP3A4 or Pgp contraindicated.
