Category: 10. Chemotherapeutic Agents

Zalcitabine (ddC) is a pyrimidine nucleoside that inhibits the replication of HIV-1. Like zidovudine, intracellular activation by triphosphorylation is catalyzed by cellular enzymes; competitive inhibition of the reverse transcriptase and chain termination result. The drug is effective as treatment for patients with HIV infection. It is available in oral formulation only and is typically prescribed…

Lamivudine (3TC) is a nucleoside analog with in vitro activity against HIV-1, including zidovudine resistant strains, and HBV. Lamivudine inhibits the reverse transcriptase of HIV-1 and is synergistic with zidovudine against HIV-1. As with zidovudine, lamivudine requires intracellular triphosphorylation for activation. Lamivudine, administered in combination with zidovudine or another nucleoside analog to retard the emergence…

Didanosine (ddI) is a synthetic analog of deoxyadenosine. It is metabolized intracellularly by a series of cellular enzymes; its active moiety, 2,3-dideoxyadenosine-5-triphosphate, inhibits viral replication by competitive inhibition of HIV reverse transcriptase and by chain termination. Pharmacokinetics: Absorption is decreased by food. Cerebrospinal fluid concentrations of the drug are approximately 20% of serum concentrations. The…

Zidovudine (AZT) is a deoxythymidine analog that requires anabolic phosphorylation for activation to the 5′-triphosphate form. After entering the cell by passive diffusion, zidovudine is phosphorylated via three cellular kinases; the triphosphate is a competitive inhibitor of deoxythymidine triphosphate for the reverse transcriptase. Additionally, it acts as a chain terminator in the synthesis of proviral…

Antiretroviral drugs are synthetic agents that have antiviral activity against HIV and are used in the management of HIV infection. There are four different classes of antiretroviral agents commercially available currently: Nucleoside reverse transcriptase inhibitors (NRTI), Protease inhibitors, Nonnucleoside reverse transcriptase inhibitors (NNRTI), and Fusion inhibitors.

Vidarabine as a 3% ointment is effective treatment for acute keratoconjunctivitis, superficial keratitis, and recurrent epithelial keratitis due to HSV. Intravenous vidarabine (10-15 mg/kg daily) is effective for treatment of HSV encephalitis, neonatal herpes, and VZV infection in immunocompromised patients. The drug is eliminated primarily by renal mechanisms as the hypoxanthine metabolite. Potential toxicities include…

Idoxuridine (IDU, IUDR) is a substituted pyrimidine analog that was the first antiviral agent to be approved. It is used topically in the treatment of herpes keratitis (0.1% solution), but because of its lack of selectivity it is too toxic for systemic administration.

Foscarnet is an inorganic pyrophosphate compound that inhibits viral DNA polymerase, RNA polymerase, or HIV reverse transcriptase directly. It has in vitro activity against HSV, VZV, CMV, EBV, HHV-6, HBV, and HIV. The drug is available in an intravenous formulation only. Cerebrospinal fluid concentrations are approximately two-thirds of steady state serum concentrations. Clearance of foscarnet…

The activated compound competitively inhibits viral DNA polymerase, causing an unstable complex, but does not result in chain termination. Ganciclovir has activity against CMV, HSV, VZV, and EBV; its activity against CMV is up to 100 times greater than that of acyclovir. Clinical Uses: Intravenous ganciclovir is indicated for the treatment of CMV retinitis in…

Acyclovir triphosphate inhibits viral DNA synthesis by two mechanisms: competitive inhibition of the viral DNA polymerase and by binding to the DNA template as an irreversible complex.. Acyclovir is available in oral, intravenous, and topical formulations. Acyclovir diffuses into most tissues and body fluids to produce concentrations that are 50-100% of those in serum. Cerebrospinal…