Gancyclovir is more effective than acyclovir against?
Correct Answer: CMV
Description: Ans. A. CMV. (Ref. H - 17th/pg. 2633; 847; 1092)Harrison's internal medicine 17th/pg. 1092.......GANCICLOVIR is an analogue of acyclovir, ganciclovir is active against HSV and VZV and is markedly more active than acyclovir against CMV.Harrison's internal medicine 17th/pg. 847 ......."With the development of highly effective oral antiviral agents, CMV immune globulin is no longer used. Ganciclovir (valganciclovir) is beneficial when prophylaxis is indicated and for the Rx of serious CMV disease. Acyclovir (Valacyclovir) is less efficacious but also less toxic than ganciclovir (Valganciclovir). The availability of Valganciclovir and Valacyclovir has allowed most centers to move to oral prophylaxis for transplant recipients. Additional oral prophylactic agents, such as maribavir, are in clinical study".# Ganciclovir, valganciclovir, foscamet, and cidofovir are approved for Rx of CMV retinitis in patients with AIDS. They are also used for colitis, pneumonia, or "wasting" syndrome associated with CMV and for prevention of CMV disease in transplant recipients.GANCICLOVIR AND VALGANCICLOVIR# An analogue of acyclovir. ganciclovir is active against HSV and VZV and is markedly more active than acyclovir against CMV.# Ganciclovir is a synthetic nucleoside analogue of 2?-deoxyguanosine. The drug is preferentially phosphorylated by virus-induced cellular kinases.# Ganciclovir triphosphate acts as a competitive inhibitor of the CMV DNA polymerase, and its incorporation into nascent viral DNA results in premature chain termination.# In HSV- and VZV-infected cells, ganciclovir is phosphorylated by virus-encoded thymidine kinases; in CMV-infected cells, it is phosphorylated by a viral kinase encoded by the UL97 gene.# Ganciclovir is approved for the Rx of CMV retinitis in immunosuppressed patients and for the prevention of CMV disease in transplant recipients. It is widely used for the Rx of other CMV-associated syndromes, including pneumonia, esophagoGI infections, hepatitis, and "wasting" illness.# Oral ganciclovir has largely been supplanted by valganciclovir, which is the L-valyl ester of ganciclovir & is frequently used in place of IV ganciclovir.- Intraocular ganciclovir, given by either intravitreal injection or intraocular implantation, has also been used to treat CMV retinitis.# Valganciclovir is well absorbed orally, with a bioavailability of 60%, and is rapidly hydrolyzed to ganciclovir in the intestine and liver. The area under the curve for a 900-mg dose of valganciclovir is equivalent to that for 5 mg/kg of ganciclovir given IV, although peak serum concentrations are -40% lower for valganciclovir. The serum half-life is 3.5 h after IV administration of ganciclovir and 4.0 h after PO administration of valganciclovir.# Valganciclovir is an orally bioavailability prodrug that can generate high serum levels of ganciclovir, although studies of its efficacy in treating CMV CNS infections are limited.Foscarnet# is a pyrophosphate analogue that inhibits viral DNA polymerases by binding to the pyrophosphate-binding site.# Foscarnet is poorly soluble and must be administered IV via an in- fusion pump in a dilute solution over 1-2 h.# Foscarnet is approved for the Rx of CMV retinitis in patients with AIDS and of acvclovir-resistant mucocutaneous HSV infections. Intraocular foscamet has been used to treat CMV retinitis.# Foscarnet has also been employed to treat acyclovir-resistant HSV and VZV infections as well as ganciclovir- resistant CMV infections, although resistance to foscarnet has been reported in CMV isolates obtained during therapy. Foscarnet has also been used to treat HHV-6 infections in immunosuppressed patients.# The major form of toxicity associated with foscamet is renal impairment. Thus renal function should be monitored closely, particularly during the initial phase of therapy.# Since foscarnet binds divalent metal ions, hypocalcemia, hypomagnesemia, hypokalemia, and hypo- or hyperphosphatemia can develop. Saline hydration and slow infusion appear to protect the patient against nephrotoxicity and electrolyte disturbances.# Foscarnet is not myelosuppressive and is active against acyclovir- and ganciclovir-resistant herpesviruses.Cidofovir# Cidofovir is a phosphonate nucleotide analogue of cytosine.# Its major use is in CMV infections. particularly retinitis. but it is active against a broad range of herpes viruses. including HSV. human herpesvirus (HHV) type 6. HHV-8. and certain other DNA viruses such as polyomaviruses. papillomaviruses. adenoviruses. and poxviruses. including variola (smallpox) and vaccinia.# Cidofovir is usually active against foscarnet-resistant CMV. although cross-resistance to foscarnet as well as to ganciclovir has been described.# Cidofovir has poor oral availability and is administered IV. It is excreted primarily by the kidney and has a plasma half- life of 2.6 h.# The major toxic effect of cidofovir is proximal renal tubular injury, as manifested by elevated se- rum creatinine levels and proteinuria. The risk of nephrotoxicity can be reduced by vigorous saline hydration and by concomitant oral probenecid. Neutropenia, rashes, and GI intolerance may also occur.# IV cidofovir has been approved for the Rx of CMV retinitis in AIDS patients who are intolerant of ganciclovir or foscarnet or in whom those drugs have failed.AMCICLOVIR AND PENCICLOVIR# Famciclovir is the diacetyl 6-deoxyester of the guanosine analogue penciclovir.# Famciclovir is well absorbed orally, has a bioavailability of 77%, and is rapidly converted to penciclovir by deacetylation and oxidation in the intestine and liver.# Penciclovir's spectrum of activity and mechanism of action are similar to those of acyclovir. Thus, penciclovir is usually not active against acyclovir-resistant viruses.# Famciclovir is effective as therapy for mucocutaneous HSV infections in HIV-infected patients.Ribavirin (Intravenous)# (15-25 mg/kg per day in divided doses given every 8 h) has been reported to be of benefit in isolated cases of severe encephalitis due to California encephalitis (LaCrosse) virus.# Ribavirin might be of benefit for the rare patients, typically infants or young children, with severe adenovirus or rotavirus encephalitis and in patients with encephalitis due to LCMV or other arenaviruses.# However, clinical trials are lacking. Hemolysis, with resulting anemia, has been the major side effect limiting therapy.TRIFLURIDINE# Trifluridine is a pyrimidine nucleoside active against HSV-1, HSV-2, and CMV.VIDARABINE# Vidarabine is a purine nucleoside analogue with activity against HSV- 1, HSV-2, VZV, and EBV.# Vidarabine inhibits viral DNA synthesis through its 5?-triphosphorylated metabolite.# IV-administered vidarabine has been shown to be effective in the Rx of herpes simplex encephalitis, mucocutaneous HSV infections, herpes zoster in immunocompromised patients, and neonatal HSV infections. Its use has been supplanted by that of IV acyclovir, which is more effective and easier to administer.
Category:
Pharmacology
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