Antiviral 1 - Hepatitis Flashcards
Differences between HBV and HCV?
Hep B: DNA virus, does integrate into host genome, vaccination is available
Hep C: RNA virus, cannot integrate into host genome, leading indication for liver transplantation/kills more than Hep B, and no vaccine available (heterogeneity hinders the development of vaccines)
Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Indications?
Hepatitis B, papillomavirus
Hep C no longer a recommended treatment
Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: How do they work?
They are antiproliferative and have immune modulating actions, increase phagocytes
Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Dosing?
Given SubQ 3 times a week for 48 weeks
Cray
Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Adverse effects?
Fever, chills, flu-like syndrome
Hypotension, chest pain, arrhythmias
GI disturbances
Leukopenia, thrombocytopenia
Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Cautions?
Caution in pulmonary disease, diabetes, coagulation disorders
Causes mood disorders - do not use in untreated or severe depression
Contraindicated in pregnancy
Which Hep B treatment is contraindicated in pregnancy?
Interferon 2 Alphas
Lamivudine: What is it?
Cytosine nucleoside
Inhibits DNA polymerase/reverse transcriptase in HBV
Lamivudine: Indications
Used in HBV in adults and children, usually treat for 1 year (doesn’t cure HBV!!)
Lamivudine: Clinical effects
Normalizes liver enzymes ~40%
Reduces hepatic inflammation ~50%
Renal elimination
Risk of lactic acidosis
Telbivudine: What is it?
Thymidine analog
Inhibits DNA polymerase/reverse transcriptase in HBV
Telbivudine: Cautions
Renal elimination
Increased risk of lactic acidosis
Telbivudine: Adverse effects
Myopathy
Peripheral neuropathy
Tenofovir, Adefovir: What are they
Adenosine analogs
Inhibit viral DNA polymerase and reverse transcriptase
Tenofovir, Adefovir: Indications
Hep B and Lamivudine resistant HBV
Also effective in HIV
Tenofovir, Adefovir: Duration
Long term treatment, doesn’t cure infection
Tenofovir, Adefovir: Adverse effects
Both cause nephrotoxicity
Tenofovir can also cause decreases in bone density
Headache, abdominal discomfort, and diarrhea at low doses
Entecavir: What is it
Guanosine nucleoside analog inhibits viral DNA polymerase and reverse transcriptase
REQUIRES INTRACELLULAR PHOSPHORYLATION
Entecavir: Counseling points
Take on empty stomach
Entecavir: Cautions
Renal elimination
Entecavir: Compared to other drugs
It is superior to lamivudine in reducing viral load
Also has limited resistance development
Describe the Hep C virus
Small, enveloped, single-stranded, positive sense RNA virus
Blood to blood contact (sharing needles, etc)
Seven major genotypes known as 1-7, divided into several subtypes with the number of subtypes depending on the genotype
Hep C virus genotypes
70% in US caused by Genotype 1
20% type 2
1% by each of the other ones
Genotype 1 is also the most common in South America and Europe
How many Hep C viruses are produced each day in an infected person?
1x10^12
Recommended therapies for Hep C 1a?
Lepidasivir and Sofosbuvir:
Paritavir/Ritonavir/Ombitasivir PLUS Dasabuvir and Ribaviron
Sofosbuvir and Simeprevir
Recommended therapies for Hep C 1b?
Lepipasivir and Sofosbuvir:
Paritavir/Ritonavir/Ombitasvir plus Dasabuvir and Ribaviron
Sofosbuvir and Simeprevir
Recommended therapies for Hep C 2?
Sofosbuvir and Ribaviron
Recommended therapies for Hep C 3?
Sofosbuvir and Ribaviron
Recommended therapies for Hep C 4?
Ledipasivir and Sofosbuvir:
Paritavir/Ritonavir/Ombitasvir plus Dasabuvir and Ribaviron
Sofosbuvir and Simeprevir
Recommended therapies for Hep C 5?
Sofosbuvir and Ribaviron
Recommended therapies for Hep C 6?
Ledipasivir and Sofosbuvir
Ledipasvir: What is it
NS5A inhibitor, alters posttranslational processing of HVC proteins
Sofosbuvir: What is it
NS5B polymerase inhibitor, mimics uridine, blocks RNA elongation
Ledipasvir, Sofosbuvir: How supplied
Fixed dose combination Harvoni
Ledipasvir, Sofosbuvir: Adverse effects
Fatigue, headache
Ledipasvir, Sofosbuvir: Drug interactions
Drug interactions with P-glycoprotein inducers (St johns wart, rifampin)
Avoid concomitant use
Ledipasvir, Sofosbuvir: Cost
12 week treatment is 95,000
24 week treatment is 189,000 (with cirrhosis)
Which drug should not be taken with Amiodarone?
Sofosbuvir - March 2015 FDA warning about severe bradycardia caused when given these drugs to patients taking amiodarone
(also worry about beta blockers)
Ledipasvir, Sofosbuvir: Monitoring
Monitor pt in hospital first 48 hours CV function, monitor at home daily for 2 weeks
Paritaprevir: What is it?
HCV NS3/4a protease inhibitor necessary for mature virus
Ombitasvir: What is it?
HCV NS5A inhibitor, used for viral replication and virus assembly
Dasabuvir: What is it?
Non-nucleoside inhibitor of RNA NS5B polymerase
Ritonavir: What is it?
Potent CYP3A4 inhibitor, prevents metabolism of Paritaprevir
Adverse effects of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir combo?
Fatigue, insomnia, pruritus
Avoid in pregnancy and breast feeding!
Simepravir: What is it?
2nd generation NS4/4A protease inhibitor, used in genotype 1, 2, 4 Hep C
Inhibits posttranslational processing of HVC proteins
Simepravir: How administered?
As combo with Ribavirin and Sofosbuvir
Simepravir: Cautions?
CYP3A4 interactions, less drug interactions and none with birth control yay
Avoid in pregnancy
Increased liver enzymes
Simepravir: Adverse effects?
Rash, photosensitivity, elevated bilirubin, myalgia, dyspnea, increased liver enzymes
