Herpes simplex virus infection topical

Bourne N, Stanberry LR, Kem ER, Holan G, Matthews B, Bernstein DI. Dendrimers, a new class of candidate topical miciobicides with activity against herpes simplex virus infection. Antimicrob Agents Chemother 2000 44 2471-2474. 

Aciclovir is phosphorylated preferentially by herpes simplex virus-coded thymidine kinase and following further phosphorylation aciclovir triphosphate interferes with herpes virus DNA polymerase and viral DNA replication. Aciclovir topical cream is indicated in the management of initial genital herpes and in limited non-life threatening mucocutaneous herpes simplex virus infections in immunocompromised patients. 

Foscarnet is an inorganic pyrophosphate analogue which causes selective inhibition of viral DNA polymerase and reverse transcriptase. Topical foscarnet cream has appeared to be a safe and effective treatment for aciclovir-unresponsive mucocutaneous herpes simplex virus infection in AIDS patients. 

Trifluoromethyl-2 -deoxyuridine, trifluridine (Viroptic ), is an anti-viral drug acting on TS via another mechanism. It is a mechanism-based inactivator of thy-midylate synthase (Figs. 27 and 28). Trifluridine is marketed for the topical treatment of Herpes simplex virus infection in eyes. 

Trifluridine (5-trifluoromethyl-2 -deoxyuridine) (Viroptic ) is marketed for the topical treatment of herpes simplex virus infection in the eyes. This antiviral drug is a mechanism-based inactivator of thymidylate synthase. The mechanism of inhibition and synthesis of trifluoridine are reported in Chapter 7. 

Topical acyclovir (Zovirax) is available as a 5% ointment topical penciclovir (Denavir), as a 1% cream for the treatment of recurrent orolabial herpes simplex virus infection in immunocompetent adults. Adverse local reactions to acyclovir and penciclovir may include pruritus and mild pain with transient stinging or burning. 

Topical acyclovir (Zovirax) is available as a 5% ointment for application to primary cutaneous herpes simplex infections and to limited mucocutaneous herpes simplex virus infections in immunocompromised patients. In primary infections, the use of topical acyclovir shortens the duration of viral shedding and may decrease healing time. In localized, limited mucocutaneous infections in immunocompromised patients, its use may be associated with a decrease in the duration of viral shedding. 

Vidarabine, an antiviral agent (10 to 15 mg/kg/day for 5 to 10 days), is indicated in the treatment of herpes simplex virus encephalitis, neonatal herpes simplex virus infections, and herpes zoster in immunosuppressed patients. In addition, vidarabine (ophthalmic ointment 3% vidarabine monohydrate [equivalent to 2.8% vidarabine]) is indicated in the treatment of acute keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus types 1 and 2, or superficial keratitis caused by herpes simplex virus that has not responded to topical idoxuridine or when toxic or hypersensitivity reactions to idoxuridine have occurred. 

Oral acyclovir is effective in primary herpetic gingivostomatitis (600 mg/m four times daily for 10 days in children) but has only modest benefit in recurrent orolabial herpes. High-dose valacyclovir (2 g twice over one day) shortens the duration of recurrent orolabial herpes by 1 day. Topical acyclovir is modestly effective in recurrent labial and genital herpes simplex virus infections. Acyclovir prophylaxis (400 mg twice daily for one week) reduces the risk of recurrence by 73% in those with sun-induced recurrences of HSV infections. Acyclovir during the last month of pregnancy reduces the likelihood of viral shedding and frequency of cesarean section in women with primary or recurrent genital herpes. 

Acyclovir (Zovirax) and penciclovir (Denavir) are the only topical antiviral dragp currently available These dragp inhibit viral replication. Acyclovir is used in the treatment of initial episodes of genital herpes, as well as heqies simplex virus infections in immunocompromised patients (patients with an immune system incapable of fighting infection). Penciclovir is used for the treatment of recurrent herpes labialis (cold sores) in adults. 

Vidarabine (adenine arabinoside, ara-A) is phos-phorylated in the cell to the triphosphate derivative which blocks DNA synthesis by inhibiting DNA polymerase. It is indicated for infections with herpes simplex virus and varicella-zoster however its use has to a large extend been surpassed by aciclovir. It is administered topically or intravenously. It is inactivated rapidly by adenosine deaminase which for systemic use necessitates constant infusion of the drug. Vidarabine is the least toxic of the purine analogues. Nausea and vomiting are the most frequent adverse effects and neurotoxicity may occur. 

Pyles, R.B., D. Higgins, C. Chalk, A. Zalar, J. Eiden, C. Brown, G. VanNest, and L.R. Stanberry. 2002. Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection. J Virol 76 11387. 

Antiviral Efficacy and Clinical Use. Vidarabine (Vira-A) was the first systemic agent used to treat herpesvirus infections, including CMV, herpes simplex virus, and varicella-zoster virus.42 In the past, this drug was administered by continuous intravenous infusion to treat severe systemic infections caused by these viruses, but systemic use of vidarabine has been replaced by safer and less toxic agents. Vidarabine is currently used primarily to treat local viral infections of the eye (e.g., herpes simplex keratoconjunctivitis) it is applied topically by ophthalmic ointment to treat these infections. 

Application in gynecology might be relevant especially as art of a larger holistic approach to serious infections and in the prevention of recurrences. This essential oil could also be a good complement for preventive and curative treatments of HPV (Human papilloma vims) and HSV (herpes simplex virus). Saro essential oil uses could be effective for minor infections and especially to prevent them in topic application (27). 

Phosphonomycin,—Yet another synthesis of phosphonomycin (22) has appeared (Scheme 6). The phosphonoaldehyde (23) was treated with pentan-3-one and cyclohexylamine to give (24), which was then converted into its oxime. Tosylation of this oxime followed by treatment with bicarbonate caused the molecule to fragment, liberating the dimethyl ester of (22). Disodium phosphonoacetic acid when administered orally or topically to mice infected with Herpes simplex virus will reduce significantly the mortality of mice caused by this virus. JV-Phosphonomethyl-glycine is a promising herbicide. Recent work has shown that it exerts its effect by inhibiting the biosynthesis of aromatic amino-acids. ... 

Three of the drugs listed (acyclovir, foscamet. trifluridine) are active against strains of herpes simplex virus. Foscamet is not used in genital infections (HSV-2) because clinical efficacy has not been established and the drug causes many toxic effects. Trifluridine is used topically, but only for herpes keratoconjunctivitis (HSV-1). The answer is (A). 

Vidarabine is used mainly in human HSV-1 and HSV-2 encephalitis, decreasing the mortality rate from 70 to 30%. Whitley et al. (57) reported that early vidarabine therapy is helpful in controlling complications of localized or disseminated herpes zoster in immunocompromised patients. Vidarabine also is useful in neonatal herpes labialis or genitalis, vaccinia virus, adenovirus, RNA viruses, papovavirus, CMV, and smallpox virus infections. Given the efficacy of vidarabine in certain viral infections, the U.S. FDA approved a 3% ointment for the treatment of herpes simplex keratoconjunctivitis and recurrent epithelial keratitis, and a 2% IV injection for the treatment of herpes simplex encephalitis and herpes zoster infections (Table 43.3). A topical ophthalmic preparation of vidarabine is useful in herpes simplex keratitis but shows little promise in herpes simplex labialis or genitalis. The monophosphate esters of vidarabine are more water-soluble and can be used in smaller volumes and even intramuscularly. These esters are under clinical investigation for the treatment of hepatitis B, systemic and cutaneous herpes simplex, and herpes zoster virus infections in immunocompromised patients. 

Nucleosides - Laboratory data on 9-p-D-arabinofuranosyladenine (Ara-A) was extensively discussed in a series of reports30,31,32,33,34,35. Ara-A was effective against herpes simplex infections of mice by IP, SC, oral and topical treatment started either prior to or after infection. Topical treatment with Ara-A of scarified hamsters eyes infected with herpes simplex prevented death and healed the eyes. Although high doses of compound were necessary, the material had a low order of animal toxicity with no mortality in mice at 7,950 mg/kg orally and an IP LD q of 4,677 mg/kg. In tissue culture antiviral activity was reported against strains of adeno, cytomegalo, vaccinia, varicella and human and simian strains of herpes viruses. The topical activity and low toxicity of Ara-A Indicate it is a promising candidate for treatment of herpes infections. 

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