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Chapter 49: Antiviral Chemotherapy & Prophylaxis

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Which statement about the mechanisms of action of antiviral drugs is accurate?

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(A) Acyclovir has no requirement for activation by phosphorylation

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(B) Ganciclovir inhibits viral DNA polymerase but does not cause chain termination

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(C) Increased activity of host cell ribonucleases that degrade viral mRNA is one of the actions of interferon-α

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(D) The initial step in activation of foscarnet in HSV-infected cells is its phosphorylation by thymidine kinase

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(E) The reverse transcriptase of HIV is 30–50 times more sensitive to inhibition by fosamprenavir than host cell DNA polymerases

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Acyclovir is activated by host cell kinases. Like acyclovir, ganciclovir inhibits viral DNA polymerase and causes chain termination. However, foscarnet inhibits viral DNA polymerase without requiring bioactivation. Fosamprenavir is the prodrug of amprenavir, an inhibitor of HIV protease; it has no significant effect on reverse transcriptase. The answer is C.

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A 30-year-old male patient who is HIV-positive and symptomatic has a CD4 count of 250/μL and a viral RNA load of 15,000 copies/mL. His treatment involves a 3-drug antiviral regimen consisting of zidovudine, didanosine, and ritonavir. The patient is taking acyclovir for a herpes infection and ketoconazole for oral candidiasis. He now complains of anorexia, nausea and vomiting, and abdominal pain. His abdomen is tender in the epigastric area. Laboratory results reveal an amylase activity of 220 U/L, and a preliminary diagnosis is made of acute pancreatitis.

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If this patient has acute pancreatitis, the drug most likely to be responsible is

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(A) Acyclovir

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(B) Didanosine

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(C) Ketoconazole

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(D) Ritonavir

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(E) Zidovudine

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Gastrointestinal problems occur with most antiviral drugs used in HIV-positive patients, and acute pancreatitis has been reported for several reverse transcriptase inhibitors. However, didanosine’s most characteristic adverse effect is a dose-limiting acute pancreatitis. Other risk factors that are relative contraindications to didanosine are advanced AIDS, hypertriglyceridemia, and alcoholism. The answer is B.

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A 30-year-old male patient who is HIV-positive and symptomatic has a CD4 count of 250/μL and a viral RNA load of 15,000 copies/mL. His treatment involves a 3-drug antiviral regimen consisting of zidovudine, didanosine, and ritonavir. The patient is taking acyclovir for a herpes infection and ketoconazole for oral candidiasis. He now complains of anorexia, nausea and vomiting, and abdominal pain. His abdomen is tender in the epigastric area. Laboratory results reveal an amylase activity of 220 U/L, and a preliminary diagnosis is ...

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