Page 877 - Basic _ Clinical Pharmacology ( PDFDrive )

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C H A P T E R

Antiviral Agents

Sharon Safrin, MD

C ASE STUD Y

A 35-year-old white woman who recently tested normal vital signs and no abnormalities. White blood
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seropositive for both HIV and hepatitis B virus surface cell count is 5800 cells/mm with a normal differential,
antigen is referred for evaluation. She is feeling well hemoglobin is 11.8 g/dL, all liver tests are within normal
3
overall but reports a 25-pack-year smoking history. She limits, CD4 cell count is 278 cells/mm , and viral load
drinks 3–4 beers per week and has no known medication (HIV RNA) is 110,000 copies/mL. What other laboratory
allergies. She has a history of heroin use and is currently tests should be ordered? Which antiretroviral medica-
receiving methadone. Physical examination reveals tions would you begin?

Viruses are obligate intracellular parasites; their replication potential targets for antiviral therapy. Recent research has focused
depends primarily on synthetic processes of the host cell. There- on identifying agents with greater selectivity, higher potency, in
fore, to be effective, antiviral agents must either block viral entry vivo stability, and reduced toxicity. Antiviral therapy is now avail-
into or exit from the cell or be active inside the host cell. As a able for herpes simplex virus (HSV), cytomegalovirus (CMV),
corollary, nonselective inhibitors of virus replication may interfere varicella zoster virus (VZV), hepatitis C virus (HCV), hepatitis B
with host cell function and result in toxicity. virus (HBV), influenza, human immunodeficiency virus (HIV),
Progress in antiviral chemotherapy began in the early 1950s, and respiratory syncytial virus (RSV). Antiviral drugs share the
when the search for anti-cancer drugs generated several new common property of being virustatic; they are active only against
compounds capable of inhibiting viral DNA synthesis. The replicating viruses and do not affect latent virus. Whereas some
two first-generation antiviral agents, 5-iododeoxyuridine and infections require monotherapy for brief periods of time (eg, HSV,
trifluorothymidine, had poor specificity (ie, they inhibited host influenza), others require multiple drug therapy for indefinite
cell DNA as well as viral DNA) that rendered them too toxic periods (HIV). In chronic illnesses such as viral hepatitis and HIV
for systemic use. However, both agents are effective when used infection, potent inhibition of viral replication is crucial in limit-
topically for the treatment of herpes keratitis. ing the extent of systemic damage.
Knowledge of the mechanisms of viral replication has provided Viral replication requires several steps (see Figure 49–1). Anti-
insights into critical steps in the viral life cycle that can serve as viral agents can potentially target any of these steps.

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