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Antiviral Drugs at a Glance
  • Antivirals are now approved for treatment of a variety of viral infections.
  • Antiviral resistance is a growing concern, especially in the treatment of human immunodeficiency virus infection.
  • Antivirals work in a number of different ways, and their spectra of activity can be very specific (amantadine) or quite broad (ribavirin).
  • The use of prodrugs of acyclovir and ganciclovir has greatly increased the oral bioavailability of these agents, which allows outpatient treatment of many herpesvirus infections.

The pace of development of new antiviral drugs has been accelerated by the human immunodeficiency virus (HIV) epidemic. Progress in our understanding of the molecular biology and pathogenesis of viral diseases has been remarkable. This chapter focuses on the antiviral drugs most likely to be used by dermatologists, as well as those that cause cutaneous side effects. The age of effective antiviral therapy is here, and they are used throughout all disciplines of medicine. We need to be prepared to evaluate patients on a wide variety of antiviral drugs, especially those currently used to treat HIV.

(See Chapters 193 and 194)

Acyclovir

Mechanism of Action

Acyclovir, 9-[(2-hydr-oxyethoxy) methyl] guanine, was the first orally available drug to be widely used for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The triphosphate form of the drug is the active form, which has a potent inhibitory effect on herpesvirus-induced DNA polymerases but relatively little effect on host cell DNA polymerase. As such, it has a tremendous margin of safety when used to treat herpetic infections. Acyclovir triphosphate causes premature termination of the nascent viral DNA chain. HSV- and VZV-induced thymidine kinases result in efficient phosphorylation of acyclovir to acyclovir monophosphate, the first step in drug metabolism. This step is not accomplished efficiently by normal cellular kinases, resulting in greater concentrations of active drug in infected cells.

Pharmacokinetics

While acyclovir is available in oral, intravenous, and topical formulations, the oral bioavailability is only in the range of 15%–30%. Excretion is almost entirely renal, with approximately 85% of renally excreted drug being unmetabolized. Because of this reliance on renal excretion, the dose must be reduced for patients with a creatinine clearance of less than 50 mL/min. Acyclovir is water soluble and achieves good levels in a variety of body fluids, including the contents of vesicles, cerebrospinal fluid, and vaginal secretions. Acyclovir has been marketed as a 5% ointment, but the efficacy is limited compared with systemic administration.

Indications

  • Treatment of symptomatic primary or recurrent mucocutaneous HSV-1 or HSV-2 infection
  • Suppression of recurrent HSV-1 and HSV-2 infections
  • Treatment of mucocutaneous HSV infections in immunocompromised patients
  • Prevention of perinatal HSV-1 and HSV-2 infection and treatment of neonatal HSV infection
  • Treatment of primary VZV infection in adults and immunocompromised children
  • Treatment of VZV infection to reduce ...

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