Anti-Viral Drugs: Hepatitis B and C Flashcards
1
Q
Chronic Hepatitis B and C
- Therapeutic Goals
- Standard of care
A
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
Q
Chronic Hepatitis B and C: Treatment
A
- 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
Q
Drugs for Hepatitis B virus:
A
- 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
Q
Tenofovir Disoproxil Fumarate
- clinical use
- MOA
- PK
A
- 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
- 1st line for:
- MOA:
- Nucleotide Reverse Transcriptase Inhibitor
- PK:
- oral
- Food enhance bioavailability
5
Q
Entecavir:
- Clinical Use
- MOA
- PK
A
- 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
Q
Telbivudine:
- Clinical Use
- MOA
- PK
A
- 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
Q
Lamivudine and Emtricitabine:
- Clinical Use
- MOA
- PK
A
- Clinical Use
- 3rd line for HBV
- Low cost=high resistance rate
- HBV/HIV co-infected w/fulminant hepatic failure
- HBV prophylaxis in HIV-infected
- 3rd line for HBV
- MOA:
- cytosine analogue reverse transcriptase inhibitors
- resistance develops rapidly via M184V/I mutation
- PK
- Emtricitabine
- prodrug for lamivudine
- Emtricitabine
8
Q
Adefovir Dipivoxil Fumurate
- Clinial Use
- MOA
- PK
A
- Clinical Use:
- 3rd line agent for HBV
- MOA:
- Reverse Transcriptase Inhibitor
- PK:
- n/a
9
Q
Hepatits B & C: Allfa Interferons: General
- MOA
- PK
- Contraindications
- Side effects
- Use cautin with patients wiith
- DDIs
A
- 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
- Initial:
- Use caution with patients that have:
- psychiatric disorders
- Epilepsy
- Thyroid disease
- Renal insufficiency
- DDIs
- Theophylline and methadone
- Increase levels of both
- Theophylline and methadone
10
Q
Pegylated Interferon
A
- 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
Q
Hepatits C: Protease Inhibitors
- drug name
- Clinical use
- MOA
- PK
- Side effects
A
- 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
Q
Hepatitis C: Polymerase Inhibitors: Sofosbuvir
- drugs
- clinical use
MOA
- PK
- side effects
A
- 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
Q
Hepatitis C: Poymerase Inhibitors
- Ribavirin
- clinical use
- MOA
- PK
- Side effects
A
- 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
- 1st line agent for Hep C
- 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
- Pregnancy Category X
14
Q
Harvoni
A
- 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
