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AT-A-GLANCE

AT-A-GLANCE

  • Antivirals are approved for treatment of a variety of viral infections.

  • Antiviral resistance is a growing concern, especially in the treatment of HIV 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 HIV (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.

DRUGS FOR THE TREATMENT OF HERPESVIRUS INFECTIONS

See Chaps. 164 and 165.

ACYCLOVIR

MECHANISM OF ACTION

See Fig. 191-1. Acyclovir, 9-[(2-hydroxyethoxy)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

Although acyclovir is available in oral, IV, and topical formulations, the oral bioavailability is only in the range of 15% to 30%, with the topical even less. Excretion is almost entirely renal, with approximately 62% of the drug remaining unmetabolized. Because of its 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 distributes widely throughout the body, including into the contents of vesicles, cerebrospinal fluid (1:2 ratio from serum concentration), and vaginal secretions. Its half-life is 4 hours in neonates, 2 to 3 hours in children 1 to 12 years old, 2 to 3.5 hours in adults, and approximately 5 hours in hemodialysis patients.

INDICATIONS

  • Symptomatic primary or recurrent HSV1/2 infections

  • Chronic suppression of HSV1/2 infections

  • HSV encephalitis

  • Primary VZV infection, including HIV associated acute retinal necrosis

  • Herpes zoster (shingles)

  • Prevention of perinatal and ...

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