Sketchy Micro: Ribavirin, Sofosbuvir, and Simeprevir

Question 1

It is important to ______________ before giving antivirals to a patient with HCV.

Answer 1

genotype their HCV strain and assess clinical stage

(Think of the word “Genotype?” written next to the yellow hippo in Dr. Liverstone’s book. Also, the microscope is looking at a liver-shaped stone.)

Question 2

What is the goal of HCV therapy?

Answer 2

Sustained virologic response (SVR): six months of tests showing no detectable HCV RNA in a patient’s blood

(Think of the calendar with six months crossed off.)

Question 3

Which patients should be considered for HCV therapy?

Answer 3

All patients with HCV detected in their blood

Question 4

The older HCV therapy included which two drugs?

Answer 4

• Weekly pegylated interferon alpha (like the radio with the alpha-shaped antenna playing once-weekly shows)
• Daily ribavirin (like the rack of ribs that the doctor eats for dinner daily)

Question 5

What is the mechanism of ribavirin?

Answer 5

It is a guanosine nucleoside analog (like the DNA strands dangling from the tent above the rib platter with the G-shaped key chain with nucleoside medallions).

Because it is a nucleoside, it needs to be phosphorylated three times before it can disrupt the growing RNA (like the three pepper shakers on the rib platter INSIDE the tent, just like how ribavirin gets phosphorylated INSIDE cells).

Question 6

What are some side effects of ribavirin?

Answer 6

• Dose-dependent hemolytic anemia (like the smashed tomatoes that fell off of the rib platter)
• Birth defects (like the teratogen tarantula)

Question 7

Ribavirin has largely been replaced by palivizumab in the treatment of _________.

Answer 7

RSV (like the RSV tombstone behind the doctor)

Question 8

What is the mechanism of sofosbuvir?

Answer 8

It is a nucleoside analog that inhibits NS5D, an RNA-dependent RNA polymerase.

(Think of the other dangling DNA strand above the SOFa in the tent.)

Question 9

Sofosbuvir’s side effects include ______________.

Answer 9

fatigue and nausea (like the guy sleeping on the sofa)

Question 10

Which drug is only effective against HCV genotype 1?

Answer 10

Simeprevir

Question 11

What is the mechanism of simeprevir?

Answer 11

It is a protease inhibitor (like the machete stuck in the tree above the guy SIMmering his soup).

Question 12

What are the side effects of simeprevir?

Answer 12

• Photosensitivity (like the old camera flashing into the woods)
• CYP inhibition (like the broken down car behind the guy simmering his soup)