Review Question - QID 217021

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Hepatitis C Drugs Introduction QID: 217021 (M1.OMB.1)

QID 217021 (Type "217021" in App Search)

A 38-year-old man presents to his primary care physician for a 6-month history of worsening abdominal pain and "yellowing" of the skin. He says that he originally thought these symptoms were a result of food poisoning but became concerned when he noticed his stools were gray and his urine was black. He was fully vaccinated as a child but has not seen a medical provider since the age of 25. He endorses heroin use for the last 15 years but has been clean for several months since starting a rehabilitation program. On physical exam, he has scleral icterus and tenderness to palpation in the right upper quadrant. He is prescribed a combination of medications and informed that the major side effects are headache, fatigue, and nausea. Which of the following is the most likely mechanism of action for the medications described?

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Inosine monophosphate dehydrogenase inhibitor

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Neutralizing immunoglobulin

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Protease inhibitor

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Reverse transcriptase inhibitor

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RNA polymerase inhibitor

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This patient who presents with signs of hepatic failure (jaundice, abdominal pain, pale stools, and dark urine) most likely has chronic hepatitis C infection given his high-risk behaviors (heroin use) and fully vaccinated status. The first-line treatment is sofosbuvir-ledipasvir of which the former is an RNA-dependent RNA polymerase inhibitor.

There are 4 medications that are currently used in the treatment of hepatitis C virus (HCV) infection. Sofosbuvir inhibits HCV RNA-dependent RNA polymerase (nonstructural protein 5B or NS5B), which is essential for viral replication. Adverse effects of this drug include headache, fatigue, and nausea. Ledipasvir inhibits the HCV nonstructural 5A (NS5A) protein, which normally functions as a viral phosphoprotein that is also necessary for viral replication. Adverse effects of this medication include headache, weakness, and fatigue. Simeprevir inhibits HCV protease (nonstructural protein 3/4A or NS3/4A), which disrupts the ability to create new viral particles. Adverse effects of this medication include rash and photosensitivity reactions. Finally, ribavirin is an older medication that inhibits inosine monophosphate dehydrogenase but has a serious side effect profile including hemolytic anemia and severe teratogenesis.

Ouzan et al. present data regarding hepatitis C treatment in the era of sofosbuvir-based treatments. They find that combination therapy had a response rate exceeding 97%.

Incorrect Answers:
Answer 1: Inosine monophosphate dehydrogenase inhibitor is the mechanism of action for ribavirin, which is also used in the treatment of chronic hepatitis C infection; however, the side effects caused by this drug are hemolytic anemia and severe teratogenesis.

Answer 2: Neutralizing immunoglobulin is used in the treatment of hepatitis A infection; however, this disease would present with acute hepatitis rather than chronic hepatic failure.

Answer 3: Protease inhibitor is the mechanism of action for simeprevir, which is also used in the treatment of chronic hepatitis C infection; however, the side effects caused by this drug are rash and photosensitivity reactions.

Answer 4: Reverse transcriptase inhibitor is the mechanism of action for tenofovir, which is used in the treatment of chronic hepatitis B infection; however, this infection is less likely in a patient who was fully vaccinated as a child.

Bullet Summary:
The mechanism of action for sofosbuvir in treating chronic hepatitis C virus infection is inhibition of the RNA-dependent RNA polymerase known as nonstructural protein 5B (NS5B).