Anti-Viral Drugs: Hepatitis B and C Flashcards Preview

Week 18 > Anti-Viral Drugs: Hepatitis B and C > Flashcards

Flashcards in Anti-Viral Drugs: Hepatitis B and C Deck (14)
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1

Chronic Hepatitis B and C

  • Therapeutic Goals
  • Standard of care

Hepatitis B:

  • Therapeutic goals 
    • Decrease Hepatitis B virus DNA to undetectable levels
    • Seroconversion of HBeAg from positive to negative
    • Reduction in liver transaminase levels
  • Standard of care:
    • HBIG vaccine or Hepislav-B 
    • Nucleoside/tide analgos (PO) and/or Peginterferons (SQ)

Hepatitis C:

  • Therapeutic goals:
    • eradicate virus

2

Chronic Hepatitis B and C: Treatment

  • Oral nucleoside/tide analogs
    • bettere tolerated than interferons
    • equial or better at suppressing virus
  • Combos
    • reduce resistance 
  • Sudden discontinuation can cause rapid increase in viral DNA levels
  • Duration of treatment: 
    • highly variable (up to 5 years or indefinitely)

3

Drugs for Hepatitis B virus:

  • HBV vaccine (HBIG)
    • recombinant hepatitis B surface antigen (HBsAg) produced in yeast 
    • Requires 3 injections then single dose every 5-10 years
  • Hepislav-B
    • New vaccine
    • use novel immune-system stimulating ingredient 
      • toll-like receptor 9 agonist 
    • aprroved by FDA for adults in 2017
    • require 2 injections
      • one month apart

Antivirals:

  • Reverse Transcriptase Inhibitors:
  • Interferons

4

Tenofovir Disoproxil Fumarate

-clinical use

-MOA

-PK

  • Clinical Use:
    • 1st line for:
      • HBV treatment in Naive patients or patients with prior exposure and drug resistance
      • HIV/HBV coninfecgted (anti-HIV activity)
      • pregant to prevent perinatal transmission
  • MOA:
    • Nucleotide Reverse Transcriptase Inhibitor
  • PK:
    • oral
    • Food enhance bioavailability 

5

Entecavir:

-Clinical Use

-MOA

-PK

  • Clinical Use:
    • 1st line for HBV
    • Potent antiviral activity
    • 1% resistance in viral polymerase in nucleoside/tide analog-naive patients
    • NOT for HBV monotherapy in co-infected patients bc it induces HIV resistance
  • MOA:
    • Reverse transcriptase inhibitors
  • PK:
    • Once a day

6

Telbivudine:

-Clinical Use

-MOA

-PK

  • Clinical use:
    • 2nd line for Heptatis B virus to reduce risk of drug resistance
  • MOA
    • Reverse Transcriptase Inhibitor 
  • PK
    • Phosphorylated to active triphosphate form
    • not a CYP450 substrate, inhibitor, inducer
    • NO DDIs reproted

7

Lamivudine and Emtricitabine:

-Clinical Use

-MOA

-PK

  • Clinical Use
    • 3rd line for HBV
      • Low cost=high resistance rate
    • HBV/HIV co-infected w/fulminant hepatic failure
    • HBV prophylaxis in HIV-infected
  • MOA:
    • cytosine analogue reverse transcriptase inhibitors
    • resistance develops rapidly via M184V/I mutation
  • PK
    • Emtricitabine
      • prodrug for lamivudine

8

Adefovir Dipivoxil Fumurate

-Clinial Use

-MOA

-PK

  • Clinical Use:
    • 3rd line agent for HBV
  • MOA:
    • Reverse Transcriptase Inhibitor
  • PK:
    • n/a

 

9

Hepatits B & C: Allfa Interferons: General

-MOA

-PK

-Contraindications

-Side effects

-Use cautin with patients wiith

-DDIs

  • MOA:
    • act as host cytokines
    • bind to cell membrane receptors
    • induce intracellular signsl that stimulate immune response by:
      • inhibition of viral life cycle
      • Expressoin of antigens
      • Phagocytosis
      • Survival of cytotoxic T cells
  • PK:
    • Varies b/w pegylated and non-pegylated alfa interferon
    • Non=short half so pegylate to increase
  • Contraindications:
    • Liver injury 
    • autoimmune disorders
    • history of cardiac arrhythmias
    • Pregnancy Category C
  • Side effects:
    • Initial:
      • flu-like syndromes
      • increase Liver enzymes
    • Long term:
      • Neurotoxicity
      • Fatigue, weight loss, reversible hearing loss, alopecia, cardiotoxicity
      • discovering a autominnue disease
        • thyroiditis
  • Use caution with patients that have:
    • psychiatric disorders
    • Epilepsy
    • Thyroid disease
    • Renal insufficiency
  • DDIs
    • Theophylline and methadone 
      • Increase levels of both

10

Pegylated Interferon

  • Contain a PEG chain that:
    • longer half-life
    • Decreases interferon clearance
    • lacks tehrapeutic activity
    • renally eliminated unchanged
  • Requires less frequent dosing
  • replaced non-pegylated as agents of choice if interferons required
  • undergohepatic metabolism
  • undergo renal + biliary excretion
    • less renal than non-pegylated
  • 2 types currently available:
    • Peg-interferon alfa-2a
    • Peg-interferon alfa-2b
  • ALL alfa interferons:
    • reserved for HCV due to side effects
    • require dose reduction in renal impairment

11

Hepatits C: Protease Inhibitors

-drug name

-Clinical use

-MOA

-PK

-Side effects

  • Telaprevir, Boceprevir, Simepravir
  • Clinical Use:
    • Triple therapy for chronic Hep C
    • ALWAYS USED WITH RIBAVIRIN
  • MOA:
    • Inhibition of HCV-specific protease
    • Stops viral replication
  • PK:
    • Food enhances absorption
  • Side effects:
    • Pregnancy category B (alone)
    • ALWAYS category X since used with ribavirin
    • Simepravir=Photosensitivity and sulfa allergy 

12

Hepatitis C: Polymerase Inhibitors: Sofosbuvir

-drugs

-clinical use

MOA

-PK

-side effects

 

  • Sofosbuvir
  • Clinical use:
    • Triple therpay for chronic Hep C
    • Extremely effective
    • Very expensive
  • MOA:
    • nucleotide analog
    • converted to nucleoside (active)
    • inhibits HCV NS5B RNA-dependent RNA polymerase
  • PK: 
    • oral
  • Side effects:
    •  well tolerated

13

Hepatitis C: Poymerase Inhibitors

-Ribavirin

-clinical use

-MOA

-PK

-Side effects

  • Clinical use
    • 1st line agent for Hep C
      • historically combined with peginterferon
    • ineffective alone
    • Adding a PI (protease inhibitor) may increase effects of interferons + Ribavirn
  • MOA:
    • nucleoside analog
    • phosphorylated by host enzymes
    • inhibit capping of viral mRNA and RNA-dependent polymerase
    • inhibits synthesis of GTP
  • PK
    • no protein binding
    • well absorved
  • Side effects:
    • Pregnancy Category X
      • avoid conception 6 months post exposure

14

Harvoni

  • combo of ledipasvir and sofosbuvir
  • used with ribavirin
  • patients with chronic HCV and HCV/HIV-1 co-infections
  • Oral-once daily 
  • High cure rates 
  • few side effects