Antiviral Agents

Acyclovir is a nucleoside analogue that is effective against HSV and VZV infections. It inhibits viral DNA replication. One phosphorylation step of acyclovir is catalyzed by the enzyme thymidine kinase. The virus-induced thymidine kinase is far more active than the host cell thymidine kinase. Therefore, acyclovir is very active against viruses within infected host cells and yet is generally well tolerated.

Table 14-3 Antifungal Agents^a

Acyclovir has proved effective in treating a variety of herpetic infections. Oral acyclovir effectively treats acute severe genital herpes and can be used for long-term suppression in immunocompetent patients with frequently recurring genital herpes. Intravenous acyclovir is effective against herpes simplex encephalitis. Acyclovir in doses of 500 mg/M² every 8 hours has been used successfully in treating herpes zoster infections in immunocompromised patients.

Oral acyclovir may be used to treat herpes zoster ophthalmicus. Doses of 800 mg 5 times daily are usually effective in reducing the incidence of ocular complications of herpes zoster ophthalmicus. However, postherpetic neuralgia is not affected by this therapy. A randomized controlled study of acyclovir and oral corticosteroids demonstrated that the latter did not help to reduce the incidence of postherpetic neuralgia when added to oral acyclovir.

Famciclovir and valacyclovir are approved in the United States for the treatment of herpes zoster and herpes simplex infections, and studies have shown that they are effective against the latter. Both of these newer drugs allow less frequent dosing intervals (every 8–12 hours, depending on the indication). Valganciclovir is used for the prevention and treatment of CMV infections in patients who have undergone organ transplantation or who have AIDS, and it has also been found to be effective for treating acute retinal necrosis caused by VZV.

Adefovir is a nucleoside analogue and a potent inhibitor of many viruses, such as HIV, HSV, hepatitis B, HPV, and EBV. The nucleoside analogue brivudine appears to have a stronger antiviral effect against VZV than does acyclovir or penciclovir. The efficacy of brivudine has been documented in several clinical trials in patients with herpesvirus-related infections, particularly herpes zoster and herpes simplex infections.

Ganciclovir, foscarnet, and cidofovir are additional antiviral agents used for treating CMV infections, including retinitis. M2 protein inhibitors amantadine and rimantadine were used previously to treat influenza but are no longer recommended due to widespread resistance. Oseltamivir, peramivir, and zanamivir are oral neuraminidase inhibitors that are used to treat and prevent influenza.

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Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.