Hepatitis Med chem Flashcards
liver functions
regulate metabolism
sythesize proteins
store vitamins and iron
degrading hormones
inactivating and excreting drugs and toxins
hepatitis =
inflammation of the liver
acute hepatitis
short-term hepatitis
immune system clears the virus from the body within 6 months
chronic hepatitis
long-term hepatitis
infection last longer than 6 months
immune system cannot clear the virus from the body
cause of acute hepatitis
viral hepatitis
non viral infection
alcohol
toxins
drugs
ischemic hepatitis
auto immune
metbolic disease
causes of chronic hepatitis
viral hepatitis
alcohol
drugs
non alocholic streahepatitis
autoimmune
heredity
viral structural
no cell wall
nucleic acid components
containing envelop-antigenic in nature
they do not have metabolic machinery of their own - uses host enzymes
stages of viral replication
cell entry attachment - penetration
uncoating
transcription of viral genome
translation
assembly of vision component
release
Hep A features
SsRNA
fecal oral transmission
Hep B features
DsDNA
parenteral transmission
sexual transmission (COMMONN)
Hep C features
SsRNA
parental transmission
sexual transmission (uncommon)
Hep D features
SsRNA
parental transmission
sexual transmission (uncommon)
Hep E features
SsRNA
fecal oral transmission
Hepatitis A Virus
picornavirus
nonenveloped
single- stranded RNA packaged in a protein shell
Hepatitis A Prevention
Immune Globulin
-preexposure: travelers to intermediate and high HAV-endemic regions
-Post-exposure: (within 14 days)
– routine: household & other inmate contacts
–selected situations: institutions, common source exposure
prevention: hep A vaccine
havrix , vaqta
Hepatitis B Virus
nuceocasod enclosed the viral DNA and a DNA polymerase that has reverse transcriptase activity similar to retroviruses
Chronic Hepatitis B infections
cirrhosis of the liver
hepatocellular carcinoma
available treatment options for chronic hepatitis B
interferons
-interferon-alpha
-pegylated interferon
nucleotide analogue antiviral agents
-lamivudine
-entercavir
-adefovir dipivoxil
-ribavirin
-telbivudine
-tenofovir
nucleoside reverse transcriptase inhibitors
-adefovir
-entecavir
-lamivudine
-telbivudine
-tenofovir
interferon-alpha
a cytokine
one of the signaling mechanism of immunomodulation
nucleoside analogs
polymerase inhibitors that target DNA elongation by inhibiting the revers transcription of HBV
-efficient, but longterm use result in drug resistance and recurrence and HBV genome can’t be eradicated
Hep B prevention:
Vaccination
-highly effective recombinant vaccine are now available
Hep B Immunoglobulin
-protect ppl who are exposed
-efficacious within 48 hours
-may give to neonates at increased risk of hep B whose mom are HBsAg and HBeAg positive
First line HBV
entecavir
tenofovir
pegylated interferon
Second line HBV
adefovir dipivoxil
telbivudine
Third line HBV
lamivudine
others: interferon alpha
Entecavir
nucleoside analoge (guanosine)
inhibiting revers transcription, DNA replication, and transcription in the replication process
not a ligand of CP450
Entecavir MOA
guanosine nucleoside analog
1: base priming
2: reverse transcription of the neg strains from the pregenomic messenger RNA
3 synthesis of the pos strain of HBV DNA
entecavir triphosphate has an inhibition of constant (ki) for HBV DNA polymerase of 0.0012uM
- weak inhibitor
Tenofovir
nucleotide analogue reverse transcriptase inhibitors (NRTIs), suppressing reverse transcriptase
induces CYPs
Tenofovir MOA
inhibits activity of reverse transcriptase by competing with the natural substrate deoxydenosine e triphosphate and after incorporation of DNA, by DNA chain termination
Tenofovir side effects
nausea
vomiting
diarrhea
asthenia (weakness, lack of energy)
DDI
Hepatitis C Virus
small
enveloped
positive single stranded RNA
Flavivirdae family
7 distinct HCV genotypes
67 subtypes
genotype 1 is most common
treatment of HCV
-protease inhibitor therapies
-interferon: chronic pts, more effective with ribavirin
-ribavirin: less experienced
major anti HCV
NS3/4A protease inhibitors
1st gen: telaprevir, boceprevir
2nd gen: simeprevir, paritaprevir, grazprevir
major anti HCV
NS5A inhibitors:
ledipasvir
ombitasvir
daclatasvir
elbasvir
velpatasvir
major anti HCV
NS5B RNA Polymerase inhibitors
nucleoside polymerase inhibitor: sofosbuvir
non-nucleoside polymerase inhibitor: dasabuvir
others: ribavirin (guanosine ribonucleic analog), pegylated interferon
two recent drugs for HCV
Harvoni
Verkira Pak
they are more specific and toxic to HCV than host cells
inhibit proteinase,NS5A, and NS5B polymerase
Harvoni
first FDA approved drug for type 1 HCV
oral
moisture of sovaldi and ledipasvir
-sofosbuvir inhibits RNA polymerase
very expensive
Viekira pak
cocktail drug
mixture of ombitasvir, paritaprevir, ritonavir and dasabuvir
most recent FDA approved
mavyret
glecaprevir/pibrentasvir
8 weeks***
a national strategy for the elimination of hep B and C
most recent FDA approved
vosevi
sofosbuvir/velpatasvir/voxilaprevir
-NS5B polymerase inhibitor, NS5A inhibitor, NS3/4A protease inhibitor
elbasvir and grazoprevir
NS5A inhibitor and protease inhibitor
glecapreveir and pibrentasvir
NS5/4A protease inhibitor and NS5A inhibitor
ledipasvir and sofosbuvir
NS5A inhibitor and nucleotide polymerase inhibitor
sofosbuvir and velpatasvir
nucleotide polymerase inhibitor & NS5A inhibitor
HAV and HBV an be protected with
vaccine and immunoglobulin
is there a vaccine for HCV
not yet
HCV infected subjects can be cured with
cocktail of anti HCV drugs
which Hepatitis virus can cause chronic liver infection and lead to cancer
HBV
HCV
