A 35-year-old woman that is currently being treated for chronic hepatitis C comes to the physician because of progressive fatigue for 10 days. Previous attempts to treat her hepatitis C infection have been unsuccessful. Examination shows pale conjunctivae. Her hemoglobin concentration is 10.1 g/dL, serum total bilirubin concentration is 1.9 mg/dL, and LDH is 259 U/L. A Coombs test is negative. Assuming her current condition is an adverse drug effect, which of the following mechanisms most likely contributes to the pharmacologic efficiency of this drug?

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Quizplus · Accepted Answer

Eductional Objective: Decreased synthesis of guanosine monophosphate (GMP), a guanine nucleotide, through the competitive inhibition of IMP dehydrogenase is one of the mechanisms of action of ribavirin. GMP is used to create viral RNA; therefore, decreased GMP synthesis leads to impaired replication of HCV. In addition, ribavirin also binds to the nucleotide-binding site of RNA polymerase, thereby further inhibiting viral replication. Ribavirin-induced hemolytic anemia results from the accumulation of phosphorylated forms of ribavirin within red blood cells; since RBCs lack dephosphorylating enzymes, ribavirin accumulates within cells, leading to hemolysis. Because of the advent of newer HCV medications, ribavirin is typically used as an adjunct in patients with refractory hepatitis C infection.

A 35-Year-Old Woman That Is Currently Being Treated for Chronic