8. Viral Hepatitis Treatment - Pharm

• treatment for chronic hep B

  • pegIFNa
  • finite duration
  • no resistance
• treatment for chronic hep B

  • nucleotide analogue
  • 1st line of therapy
  • inhibit HBV polymerase
• nucleoside analogue can treat both - HBV and HIV
• Interferon - cytokines: IFN, IL and TNF-a
• Interferon can be used to treat - hepatitis and cancer
• INF-a ADE

  • flu like syndrome
  • neuropsychiatric reaction
  • bone marrow suppression
  • hypothyroidism
• INF-a: bone marrow suppression and thrombocytopenia - treatment

  • G-CSF and GM-CSF
• INF-a: C/I

  • liver disease
  • hematological toxicity
  • autoimmune disorder
  • pregnant
• INF-a should not be used in

  • uncontrolled depression
  • IM transplant pts
• INF-a use

  • chronic hepatitis B and C
• what drug is used for Chronic HCV?

  ribavirin + INF-a
• preferred treatment of HBV infection with ongoing HBV DNA replication and liver inflammation?

  INF-a
• What is used for chronic HBV - in compensated liver disease?

  pegylated INF-a - bc it lacks drug resistance

  • combine with Entecavir + Tenofovir
• What to monitor when giving INF-a?

  • CBC
  • TSH
• Name of nucleoside reverse transcriptase inhibitors - NRTIs?

  • Entecavir
  • Tenofovir
• Entecavir MOA

  • inhibit 3 function of HBV DNA polymerase
  • suppresses HBV DNA levels
• Entecavir use

  • chronic HB infection with
  • active viral replication
  • high serum ALT
• Tenofovir MOA

  • inhibit reverse transcriptase enzyme
• Tenofovir ADE

  • acute renal failure
  • Fanconi's syndrome - malabsorption of electrolytes in kidney
• Tenofovir

  • can develop renal failure
  • monitor
  • serum creatinine + phosphorous level
  • loss of Ca2+ and vitamin D - leading to bone loss
• Nucleotide analogue - first line for decompensated and compensated liver

  • entecavir + tenofovir
• PEG IFN-a - used in younger pt with compensated liver disease
• what is used as the main treatment of HCV?

  DAA with ribavirin
• NS3/NS4A protease inhibitors - prevent the selective cleavage of polyproteins into individual viral active proteins
• NS3/NS4A protease inhibitors

  • Simeprevir - increase elevations in bilirubin
  • Paritaprevir - increase ALT
• sofosbuvir - target the catalytic site of NS5B
• Dasabuvir (NS5B Inhibitors)

  • don't administer with inducers of CYP3A
• Sofosbuvir (NS5B Inhibitors)

  • don't administer with potent P-gp inducers = decrease concentration
• Ribavirin is also combined with DAAs to increase antiviral activity in HCV
• Ribavirin MOA

  • inhibit IMP causing mutation in viral mRNA = ineffective viral translation
• Ribavirin inhibits the replication of DNA and RNA viruses
• HCV infection - use ribavirin with

  • Interferons-α
  • DAAs to increase their antiviral activity.
• Ribavirin ADE

  • Hemolytic anemia
• ** Ribavirin MOA

  • inhibit IMP dehydrogenase causing ineffective viral translation
  • combined with DAA to increase antiviral activity