Varicella-zoster virus acyclovir

Pharmacology Valacyclovir is the hydrochloride salt of L-valyl ester of the antiviral drug acyclovir. Valacyclovir is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against herpes simplex virus types I (HSV-1) and II (HSV-2), and varicella-zoster virus (VZV). In cell culture, acyclovir has the highest antiviral activity against HSV-1, followed by (in decreasing order of potency) HSV-2 and VZV. In vitro, acyclovir triphosphate stops replication of herpes viral DMA in 3 ways 1) Competitive inhibition of viral DMA polymerase 2) incorporation and termination of... 

Unlabeled Uses Treatment of acyclovir-resistant herpes simplex virus, adenovirus, foscarnet-resistant CMV, ganciclovir-resistant CMV, varicella-zoster virus... 

Mechanism of Action Avirustatic antiviral that is converted to acyclovir triphosphate, becoming part of the viral DNA chain. Therapeutic Effect Interferes with DNA synthesis and replication of herpes simplex virus and varicella-zoster virus. Pharmacokinetics Rapidly absorbed after PO administration. Protein binding 13%-18%. Rapidly converted by hydrolysis to the active compound acyclovir. Widely distributed to tissues and body fluids (including cerebrospinal fluid CSF ). Primarily eliminated in urine. Removed by hemodialysis. Half-life 2.5-3.3 hr (increased in impaired renal function). 

Acyclovir (ACV) is not a true nucleoside, because the guanine residue is attached to an open-chain structure, but it mimics deoxyribose well enough for the compound to be accepted as a substrate by a thymidine kinase specified by certain herpes-type viruses. The normal thymidine kinase in mammalian cells does not recognize ACV as a substrate, however, so only virus-infected cells convert ACV to its monophosphate. Once the first phosphate has been added, the second phosphate is added by cellular guanylate kinase several other cellular kinases can add the third phosphate. The triphosphate is a more potent inhibitor of the viral DNA polymerases than of cellular DNA polymerases and also inactivates the former but not the latter. The net result is that ACV has been an effective treatment of, and prophylaxis for, genital herpes. Also it can result in dramatic relief of pain associated with shingles caused by reactivation of latent varicella-zoster virus, and has been successful in many patients with herpes encephalitis. 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Penciclovir [pen SIK lo veer] is an acyclic guanosine nucleoside derivative that is active against herpes simplex virus Types I and II, and against varicella-zoster virus. Penciclovir is only administered topically (Figure 37.8). Penciclovir is monophosphorylated by viral thymidine kinase, and cellular enzymes form the nucleoside triphosphate, which inhibits herpes DNA polymerase. Penciclovir triphosphate has an intracellular half-life 20 to 30 times longer than does acyclovir triphosphate (see p. 365). Penciclovir is negligibly absorbed from topical application, and is well tolerated. Both healing and pain are shortened approximately one-half day in duration, compared to placebo-treated subjects. 

Keywords Encephalitis Heipes simplex virus type 1 Varicella zoster virus Cytomegalovirus West Nile virus Acyclovir Valacyclovir Ganciclovir Cidofovir Famciclovir Foscamet Latencyneurological disorders Lifecycle... 

Varicella-zoster virus Skin, disseminated disease Acyclovir 10 mg/kg every 8 h foscarnet 60 mg/kg every 8 h... 

Jacobson M, Berger T, Fikrig S, et al. Acyclovir-resistant varicella-zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1990 112 187-191. 

Cidofovir is an acyclic nucleotide analogue of the monophosphate of cytosine. When phosphorylated by host cellular enzymes, the active compound cidofovir diphosphate has broad activity against the herpes viruses, including CMV, herpes simplex viruses 1 and 2, varicella zoster virus and Epstein-Barr virus. Cidofovir is used primarily in treatment of CMV retinitis in patients who have failed treatment with ganciclovir or foscamet and in acyclovir-resistant herpes simplex infections. 

Famciclovir, the oral formulation of penciclovir, is a new antiherpes agent that is well absorbed following oral administration with little intersubject variability, and is rapidly converted to penciclovir with a bioavailability of 77%. Furthermore, although the activities of penciclovir and acyclovir against varicella-zoster virus (VZV) in infected cell lines appear to be comparable, penciclovir-triphosphate persists in virus-infected cells far longer than acyclovir-triphosphate, resulting in more prolonged antiviral activity. The intracellular half-life of penciclovir-triphosphate in VZV-infected cells is reported to be 9 hours, whereas that of... 

Foscamet is an antiviral agent that inhibits replication of all known herpes viruses, including cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Epstein-Barr virus (EBV) and varicella-zoster virus (VZV). It is indicated in the treatment of CMV retinitis in patients with AIDS treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients and as combination therapy with ganciclovir for patients who have relapsed after monotherapy with either drug. 

The first systemically administered antiherpesvirus agent, vidarabine, was approved by the Food and Drug Administration (FDA) in 1977. However, its toxicities restricted its use to life-threatening infections of HSV and varicella-zoster virus (VZV). The discovery and development of acyclovir, approved in 1982, provided the first effective treatment for less severe HSV and VZV infections in ambulatory patients. Intravenous acyclovir is superior to vidarabine in terms of efficacy and toxicity in HSV encephalitis and in VZV infections of immunocompromised patients. Acyclovir is the prototype of a group of antiviral agents that are phosphorylated intraceUularly by a viral... 

Vidarabine Vidarabine is an adenine analog and has activity against HSV, VZV, and CMV. Its use for systemic infections is limited by rapid metabolic inactivation and by marked toxic potential. However, it has been used intravenously for severe HSV infections, including those resistant to acyclovir, and it also prevents the dissemination of varicella-zoster virus in immunocompromised patients. Vidarabine is used topically for herpes keratitis, but it has no effect on genital lesions. Toxic effects with systemic use include gastrointestinal irritation, paresthesias, tremor, convulsions, and hepatic dysfunction. Vidarabine is teratogenic in animals. 

Acyclovir (Zovirax) Metabolized by thymidine kinase and other enzymes to triphosphate analog which inhibits DNA polymerase and incorporates into viral DNA. Binds to viral thymidine kinase with higher affinity than it binds to mammalian thymidine kinase. Herpes simplex 1 and II and varicella zoster virus. 

Shepp DH, Dandliker PS, Meyers ID. Treatment of varicella-zoster virus infection in severefy immunocompromised patients arandomizedcompaiisonof acyclovir and vidarabine. NEr l JMed 9 314,208-12. 

Acyclovir is widely used to inhibit several herpes viruses, particularly HSV-1 and HSV-2 [32-34], It is also used to treat varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The inhibitory activity of acyclovir is highly selective. Thus, acyclovir is a first line antivirial drug. 

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