Lecture 5: Drugs for Hepatitis Flashcards
What indicates viral load?
HCV RNA in the blood
If the RNA is undetectable after 12 wks of treatment with hepatitis drugs what does that indicate?
SVR (Sustained Virologic Response) –> aka a cure
What type of drug is Ribavirin?
What other drug can it be used in combination with?
Guanosine analog –> mimics guanosine & tricks HCV into using it to replicate
used in combo w/interferons
MOA for Ribavirin?
Blocks the capping of viral RNA –> inhibits viral RNA-dependent polyermerase –> induces mutations in the viral RNA –> RNA becomes unfunctional
What is the major toxicity associated w/Ribavirin?
Hemolytic anemia
Other than HCV treatment what is Ribavirin also used for?
- influenza A & B
- parainfluenza
- RSV
- HIV-1
What type of drug are interferons?
Cytokines that bind to membrane receptors
Once the interferon alpha binds to the membrane receptor what does it cause?
It induces intracellular signals –> inhibit viral penetration, transcription, translation & protein processing, maturation, and release
What are the 3 major effects of interferons based on its MOA? Overall result?
Note: has a direct effect on the virus
- incr MHC antigens
- incr phagocytic activity of macrophages
- incr proliferation/survival of cytotoxic T cells
OVERALL: ramps up the immune system to stop the virus
What is the major toxicity associated with interferons?
BAD flu like symptoms –> non adherence
reason why these drugs hardly ever used
Other than HCV treatment what are interferons also used for?
HBC and tumors (anti-tumor activity)
b/c they exert antiviral, immunomodulatory & anti-proliferative actions
CIs to using interferons?
- Hepatic decompensation
- Autoimmune dz
- Hx of cardiac arrhythmia
- Severe depression
- Pregnancy
What type of drug is Simpreprevir?
HCV Protease inhibitor –> targets NS3/4A protease
What are the major toxicities/AEs associated w/Simpreprevir?
- Rash**
- Photosensitivity**
- incr bilirubin/uric acid
- CI in combo w/ interferons/ribavirin in pregnancy
- Drug-Drug interactions w/ statins**(rosuvastatin/atorvastatin)
Use for Simpreprevir?
HCV genotype 1
Note: better response than interferon/ribavirin alone
What drug is the prototype for HCV Polymerase/NS5B inhibitors? What type of drug is it?
Sofosbuvir
- uridine analog
What is the MOA for Sofosbuvir?
Targets RNA-dependent HCV RNA polymerase activity
(binds to NS5B protein) –> block RNA synthesis
What type of patients should not receive Sofosbuvir?
Pts w/severe renal dysfunction –> d/t increased exposure
Note: well tolerated, most toxicities are d/t peg/ribavirin combinations
What kind of drugs should not be combined w/ Sofosbuvir? Why?
P-gp inducers (rifampin)
- b/c Sofosbuvir is a P-glycoprotein transporter substrate
What types of HCV is Sofosbuvir used for?
ALL genotypes and those resistant to PIs
When is Sofosbuvir is 1st line tx?
Sofosbuvir is 1ST LINE TX IN COMBO w/ledipasivir, Ribavirin, or Peginterferons
How is Sofosbuvir given to kids > 12 y/o or 77+ lbs?
- Sofosbuvir given alone for genotypes 2/3
- Sofosbuvir + ledipasvir for genotypes 1, 4, 5, 6
What drug is the prototype for NS5A inhibitors?
Ledipasvir
What is the MOA for Ledipasvir?
Targets the NS5A protein
Thought to:
- block replication (interacts w/NS5B) by preventing RNA from binding to polymerase
- inhibit viral assembly andrelase
