Antivirals ganciclovir

IMIPENEM WITH CILASTATIN ANTIVIRALS - GANCICLOVIR/ VALGANCICLOVIR t adverse effects (e.g. seizures) Additive side-effects these drugs can cause seizure activity Avoid combination if possible use only if benefit outweighs risk... 

In this context, it should be noted that the specific antiviral activity of ganciclovir against HSV (which is more potent than that of acyclovir) can be fully explained by the compound being specifically recognized as substrate by the HSV-encoded TK. For CMV, however, which does not encode a virus-specified TK, the activity of ganciclovir depends on the phosphorylation by a vims-encoded protein kinase, which... 

Golankiewicz B, Ostrowski T, Goslinski T, Januszczyk P, Zeidler J, Baranowski D, De Clercq E (2001) Fluorescent tricyclic analogues of acyclovir and ganciclovir. A structure-antiviral activity study, J Med Chem 44 4284 287... 

Stuyver LJ, McBrayer TR, Thamish PM, Qark J, HoUecker L, Lostia S, Nachman T, Grier J, Bennett MA, Xie M-Y, Schinazi RE, Morrey JD, Inlander JL, Eurman PA, Otto MJ (2006) Inhibition of hepatitis C repUcon RNA synthesis by P-D-2 -deoxy-2 -fluoro-2 -C-methylcytidine a specific inhibitor of hepatitis C virus replication. Antiviral Chem Chemother 17 79-87 Sullivan V, Talarico CL, Stanat SC, Davis M, Coen DM, Biron KK (1992) A protein kinase homo-logue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature 359 85... 

Acyclovir (acycloguanosine. Fig. 5.221) is a novel type of nucleoside analogue which becomes achvated only in herpes-infected host cells by a herpes-specific enzyme, thymidine kinase. This enzyme inihates conversion of acyclovir initially to a monophosphate and then to the antiviral triphosphate which inhibits viral DNA polymerase. The host cell polymerase is not inhibited to the same extent, and the antiviral triphosphate is not produced in uninfected cells. Ganciclovir (Fig. 5.22J) is up to 100... 

Pharmacology Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases and reverse transcriptases at concentrations that do not affect cellular DNA polymerases. CMV strains resistant to ganciclovir may be sensitive to foscarnet. Acyclovir- or ganciclovir-resistant mutants may be resistant to foscarnet. 

The topical ophthalmic antiviral preparations appear to interfere with viral reproduction by altering DNA synthesis. Trifluridine is effective treatment for herpes simplex infections of the conjunctiva and cornea. Ganciclovir is indicated for use in immunocompromised patients with cytomegalovirus (CMV) retinitis and for prevention of CMV retinitis in transplant patients. Foscarnet is indicated for use only in AIDS patients with CMV retinitis. 

The trifluridine monograph follows this introduction. Prescribing information for foscarnet and ganciclovir appear in the Antivirals section of the Anti-Infectives chapter. 

Class L-valyl ester prodrug of ganciclovir, synthetic analogue of 2 -deoxyguanine, with antiviral properties against herpes including human cytomegalovirus... 

Cheng, L., et al. 2000. Intravitreal toxicology and duration of efficacy of a novel antiviral lipid prodrug of ganciclovir in liposome formulation. Invest Ophthalmol Vis Sci 41 1523. 

Foscarnet and ganciclovir are two antiviral drugs, which are investigated as candidates for iontophoretic administration for local treatment of cytomegalovirus (CMV) retinitis, which is most common in AIDS patient. These two drugs were successfully delivered into the vitreous, where high therapeutic levels were maintained for up to 24 h in the case of ganciclovir [76] and for 60 h after foscarnet delivery [78]. 

Antiviral Efficacy and Clinical Use. Fomivirsen (Vitravene) is injected into the vitreous humour to treat CMV infection in the eye.42 This drug is often used to treat ocular CMV infections that are resistant to more traditional agents such as ganciclovir or fos-carnet. 

Mechanism of Action. Foscarnet works somewhat like acyclovir and ganciclovir that is, foscarnet inhibits the DNA polymerase enzyme necessary for viral DNA replication. Foscarnet differs from these other antiviral drugs, however, in that it does not require phosphorylation (activation) by enzymes such as viral thymidine kinase. Certain strains of viruses are thymidine-kinase deficient, meaning that these viruses lack the enzyme needed to activate antiviral agents... 

Antiviral actions of purine and pyrimidine analogs. Acyclovir and ganciclovir (top) are phosphorylated first by viral kinase to the monophosphate. This intermediate and the drugs shown on the left are then phosphorylated by host cell kinases to the nucleotide analogs that inhibit viral replication. (Modified and reproduced, with permission, from Trevor AT, Katzung BG, Masters SM Pharmacology Examination Board Review, 6th ed. McGraw-Hill, 2002.)... 

Antiviral spectrum Its activity in vitro is the same as that of acyclovir, but ganciclovir is approved only for treatment of cytomegalic retinitis. 

Famciclovir [fam SYE kloe ver], another acyclic analog of 2 -deoxyguanosine, is a prodrug that is metabolized to the active pen-ciclovir (pen SYE kloe ver). The antiviral spectrum is similar to that of ganciclovir but it is presently approved only for treatment of acute herpes zoster. The drug is effective orally. Adverse effects include headaches and nausea. Studies in experimental animals have shown an increased incidence in mammary adenocarcinomas and testicular toxicity. 

MYCOPHENOLATE ANTIVIRALS -ACICLOVIR, GANCICLOVIR t plasma concentrations of both drugs. Toxic effects of both drugs likely Attributed to competition for renal tubular excretion Monitor blood counts - For signs and symptoms of immunosuppression, see Oinical Features of Some Adverse Drug Interactions, Immunosuppression and blood dyscrasias... 

MYCOPHENOLATE ANTIVIRALS-ACICLOVIR, GANCICLOVIR Possible T efficacy Competition for renal excretion Monitor renal function, particularly if on >4g valacidovir. 1 dose of acidovir if there is a background of renal failure... 

PROBENECID ANTIVIRALS t levels of acidovir, valacidovir and ganciclovir Competitive inhibition of renal excretion Care with co-administering probenecid with /r/g/r-dose antivirals... 

DRUGS TO TREAT INFECTIONS ANTIVIRALS - OTHER Ganciclovir, valgancidovir... 

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