Medical Pharmacology Chapter 36:  Antiviral Drugs

• Antiviral Drugs

  • Drugs Used in treating Herpes Viral Infections and related agents

    • Docosanol (Abreva)

    •  

      Docosanol (Abreva)⁸

      Space-filling model of the docosanol molecule.8

    • Docosanol (Abreva) inhibits fusion between the cell plasma membrane and the herpes simplex viral envelope.³ 

      • As a result viral entry into cells and consequently viral replication is prevented.

      • This drug, a saturated 22-carbon aliphatic alcohol, is available for topical administration, as a 10% cream.

      • In treating recurrent oral labial herpes, healing time is reduced by about 18 hours.³

    • Docosanol is not a virucidal drug in is typically not viewed as a true antiviral.⁴ 

      • In the 10% cream formulation docosanol (Abreva) was the first herpes simplex virus treatment sold as an over-the-counter product.⁴  

      • Docosanol appears to exhibit preferential activity against lipid-enveloped viruses that use fusion mechanisms for entering target cells, compared to non-enveloped viruses.

        • Additionally, Docosanol does not influenced binding of herpes simplex virus to herpes simplex virus-specific target cell receptors.

          • Classical antiviral drugs inhibit viral DNA replication, a process allowing for HSV genomic mutations.

          • Since docosanol does not directly inhibit viral DNA replication, development of resistance to docosanol is unlikely.⁴  

      • Docosanol exhibits activity against enveloped viruses such as herpesviruses type 1 (HSV-1), herpesvirus type 2 (HSV-2) cytomegalovirus, influenzae virus, human herpesvirus-6, and respiratory syncytial virus (RSV).⁴ 

    • Idoxuridine (Dendrid)

      • Idoxuridine

      • Idoxuridine (Dendrid), a viricidal drug, is an iodinated thymidine analog.¹ 

        • This agent appears to inhibit replication of DNA viruses including herpesviruses and poxviruses.

        • Idoxuridine is not a selective agent since low concentrations inhibit the growth of both infected and uninfected cells.

          • Accordingly, the drug is incorporated into both viral and cellular DNA, inhibiting DNA synthesis.

            • DNA modified by incorporation of this analog appears more susceptible to breakage and more predisposed to transcription errors.¹  

        • Resistance to the effects of idoxuridine has been noted both in vitro and verified in viral isolates obtained from idoxuridine-managed HSV keratitis patients.¹  

      • In the United States, idoxuridine is approved solely for topical (ophthalmic) management of HSV keratitis.¹  

        • Outside the US idoxuridine as the dimethyl sulfoxide is used for topical treatment of:

          • Herpes labialis

          • Genitalis and

          • Varicella-zoster.

      • Topical idoxuridine, in treating ocular HSV infection, is more effective in epithelial infections than in stromal infections.

        • Epithelial infection typically improves within a few days.⁵

          • Treatment should extend about 3 or 4 days after apparent healing.

          • Often ophthalmologists still prefer to denude affected corneal epithelium and do not use idoxuridine.⁵

        • Adverse effects include itching, pain, inflammation and edema affecting the eye or lids.¹ 

      • A clinical study comparing acyclovir versus idoxuridine for treatment of epithelial herpes simplex keratitis was performed in the early 1980s.⁶ 

        • In that study 30 patients were randomized to the acyclovir group and 34 patients randomized to the idoxuridine group.⁶ 

          • These patients exhibited epithelial herpetic keratitis and the clinical trial evaluated these drugs for both efficacy and adverse reactions.⁶ 

            • Patients were treated either with 3% acyclovir ophthalmic ointment or 0.5% idoxuridine ophthalmic ointment five times a day for two weeks.

            • The trial results reported no difference between acyclovir and idoxuridine as antiviral agents for treating epithelial herpetic keratitis.

              • Factors considered included overall healing patterns, presenting conditions, duration of symptoms, prior ophthalmic steroid use and positive pretreatment herpes virus culture.

              • The only difference found was an increase likelihood with idoxuridine for development of an adverse reaction, superficial punctate epitheliopathy.⁶

                •  

                  "Punctate Epithelial Erosions"

                  Image Attribution:  The McGraw-Hill Companies, Inc, 2006