Pharm- Hepatitis Flashcards
Agents for HBV
Entacavir
Tenofovir
Peginterferon alfa
Agents for HCV
Simeprevir Daclatasvir Sofosbuvir Dasabuvir Ribavirin
Transmission of HAV
fecal-oral
Transmission of HBV
sexual
parenteral
perinatal
Transmission of HCV
sexual
parenteral
perinatal
HBsAg
high levels occur during acute or chronic infection.
If found, the patient is infectious!
Normal immune response produces Ab’s to this Ag
We use this to make the HBV vaccine
anti-HBs
Recover or immunity from HBV
Also arise after successful vaccination
Anti-HBc (total HBC core Ab)
Appears at onset of infection
Will persist for life
Indicates previous or ongoing infection
IgM anti-HBc
Recent (acute) infection <6mths
HBeAg
High levels of HBV
Found during acute and chronic infection
Indicates viral replication
HBeAb
Lower levels of HBV
Immune system may produce them after an acute infection or after a burst in viral replication.
Seroconversion (Ag –> Ab) is a good predictor of viral clearance in pt’s receiving treatment
Goal of HBV therapy
decrease morbidity and mortality
Goal of HCV therapy
Viral eradication (sustained viral response- SVR)
Sustained viral response
viral eradication, the absence of HCV RNA by PCR for 12wks after completion of therapy
Advantages of IFNa compared to NA’s
Finite treatment duration
No resistance issues
Durable response
Disadvantages of IFNa compared to NA’s
Side effects
Cannot be used for pt’s with decompensated liver dz
Advantages of NA’s compared to IFNa
PO administration
Better tolerated
High response rate
Can be used for pt’s with decompensated liver dz
Disadvantages of NA’s compared to IFNa
?sustained response
Resistance
Side effects (peripheral neuropathy, lactic acidosis, hepatic steatosis)
MOA of IFNa
cytokine! So inhibits everything…
Antiviral, immunomodulatory, and anti-proliferative actions. Inhibits viral penetration, translation, transcription, protein processing, maturation, and release. Enhanced phagocytic activity of macrophages and augmentation of proliferation/survival of cytotoxic T-cells.
PK of peg-IFNa
“peg” = increased half life, slows clearance
ADR’s of IFNa
flu-like symptoms transient increase in LFT's Neurotoxicity Myelosuppresion Fatigue
C/I of IFNa
decompensated liver dz
Psych pt’s
Pregnancy
DDI’s of IFNa
Theophylline
Methadone
MOA of Entacavir
guanosine analog, inhibits DNA polymerase
Use of Entacavir
1st line treatment of HBV
ADR’s of Entacavir
HA fatigue rash nausea dizziness
MOA of Tenofovir
adenosine analog, inhibits DNA polymerase
Use of Tenofovir
1st line treatment of HBV
ADR’s of Tenofovir
N/V/D
decreased bone mineral density
NS3/4 Protease Inhibitors
Simeprevir
“-previr”
NS5A Protease Inhibitors
Daclatasvir
“-asvir”
NS5B RNA-Dependent RNA Polymerase Inhibitors
Sofosbuvir - Nucleot(s)ide Polymerase Inhibitors
Dasabuvir - Non-Nucleoside Polymerase Inhibitor
“-buvir”
MOA of Daclatasvir
binds N-terminus of NS5A, thereby inhibiting viral RNA replication and virion assembly
PK of Daclatasvir
CYP3A metabolism (C/I when on CYP3A inducers)
ADR’s of Daclatasvir
Fatigue
HA
N/D
increased lipase
MOA of Ledipasvir(-sofosbuvir)
inhibits NS5A protein necessary for viral replication; also acts as a chain terminator
ADR’s of Ledipasvir(-sofosbuvir)
Insomnia!!!
Fatigue, HA, N/D, increased serum lipase
MOA of Ombitasvir-paritaprevir-ritonavir + dasabuvir
Ombitasvir- inhibits NS5A
Paritaprevir- inhibits NS3/4A (polyprotein cleavage)
Dasabuvir- inhibits RNA-dependent RNA polymerase
Ritonavir- CYP3A inhibitor to increase plasma concentrations of the other drugs
PK of Ombitasvir-paritaprevir-ritonavir + dasabuvir
CYP metabolism
All are excreted in feces
ADR’s of Ombitasvir-paritaprevir-ritonavir + dasabuvir
Pruritus/skin reactions
Asthenia (generalized weakness)
Elevated ALT
Fatigue, HA, nausea, insomnia
MOA of Sofosbuvir
inhibits NS5B RNA dependent RNA polymerase, acts as a chain terminator
PK of Sofosbuvir
80% excreted in urine, substrate of P-glycoprotein
ADR’s of Sofosbuvir
Anemia
Neutropenia
Myalgia
Fatigue, HA, insomnia, pruritus, N/D, flu-like symptoms, weakness
MOA of Simeprevir
inhibits NS3/4A protease
PK of Simeprevir
CYP3A4 oxidative metabolism, excreted in feces
ADR’s of Simeprevir
Pruritis/skin rash
Nausea
Myalgias
Increased serum bilirubin
DDI’s of Simeprevir
avoid with CYP inducers i.e. rifampin
may increase concentration of other CYP3A4 substrates i.e. statins
MOA of Ribavirin
guanosine analog; inhibits initiation/elongation of RNA
Therapeutic uses of Ribavirin
Chronic HCV Influenza A and B Parainfluenza RSV Paramyxoviruses HIV-1
ADR’s of Ribavirin
hemolytic anemia
depression
fatigue, nausea, rash, insomnia
C/I’s of Ribavirin
anemia
ESRD
ischemic vascular disease
pregnancy (teratogenic)
CYP associations
Metabolized by CYP
- Daclatasvir
- Ombitasvir-paritaprevir-ritonavir plus dasabuvir
- Simepravir
CYP3A is inhibited by Ritonavir
