Nursing Pharmacology:  Antiviral Drugs

• Antiviral Drugs

  • Drugs Used in treating Herpes Viral Infections and related agents

    • Docosanol (Abreva)

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

        • This agent appears to inhibit replication of DNA viruses including herpes viruses 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

References

Acosta EP Flexner C Antiviral Agents (Nonretroviral) Chapter 58 in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition (Brunton LL Chabner BA Knollmann BC, eds; Brunton LL, ed; Blumenthal DK  Murri N Hilal-Dandan R, assoc eds, Knollmann BC, consulting ed, on-line edition) The McGraw-Hill Companies, 2011. Baden LR Dolin R, Chapter 178, Antiviral Chemotherapy, Excluding Antiretroviral Drugs, in Harrison's Online   (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.),  Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Safrin S Antiviral Agents, Chapter 49 in Basic & Clinical Pharmacology, 12 e (Katzung BG Masters SB Trevor AJ) The McGraw-Hill Companies, 2012 (on-line edition) Drug Monograph:  Docosanol (Abreva) ClinicalKey (Drug information provided by Gold Standard. Flach AJ Fraunfelder FW Chapter 22.  Opthalmic Therapeutics (in Vaughan & Asbury's General Ophthalmology, 18e, Riordan-Eva P Cunningham Jr ET, eds)  The McGraw-Hill Companies, 2011, on-line edition. McCulley JP Binder PS Kaufman HE O'Day DM Poirier RH A double-blind, multicenter clinical trial of acyclovir vs idoxuridine for treatment of epithelial herpex simplex keratitis Ophthalmology 89(10):  1195-1200, October 1982.

 

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