Antiviral Chemotherapy Prophylaxis

Purine, pyrimidine anaiogs reverse transcriptase inhibitors 

Pharmacokinetics Acyclovir can be administered by the topical, oral, and intravenous routes. Renal excretion is the major route of elimination of acyclovir and dosage should be reduced in patients with renal impairment. 

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Mechanisms Foscarnet is a phosphonoformate derivative that does not require phosphorylation for antiviral activity. Though it is not an anti metabolite, foscarnet inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase. A known mechanism of resistance involves point mutations in the DNA polymerase gene. 

Pharmacokinetics Foscarnet is given intravenously and penetrates well into tissues, including the CNS. Up to one-third of a dose may be deposited in bone. The drug undergoes renal elimination in direct proportion to creatinine clearance. 

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Other Bacterial vaccines and toxoids 1 Viral vaccines J Rickettsial vaccines Antisera Antiviral protein (interferon) Prophylaxis Therapy Chemotherapy Subunit vaccines sometimes available... 

The origins of antiviral therapies can be traced to the early 1950s, when sulfonamide antibiotics were tested for activity against poxviruses using mice infected with vaccinia (1). A decade of work at the Wellcome laboratories culminated in the development of methisazone, which was introduced in 1960 for the prophylaxis of smallpox (see Scheme 1). Notable success in the smallpox epidemic in Madras in 1963 demonstrated the value of this compound, but vaccines introduced soon after led to eradication of the disease and made the compound redundant. However, the principle that chemotherapy was effective for treating antiviral diseases had been demonstrated. 

Immunocompromised patients are at greatest risk for severe and recurrent HSV infections. Acyclovir, valacyclovir, and famciclovir have been used to prevent reactivation of infection in patients seropositive for HSV who undergo transplantation procedures or induction chemotherapy for acute leukemia. Immunocompromised individuals, such as patients with AIDS, who fail treatment or prophylaxis with recommended antiviral doses frequently demonstrate improved response with higher doses. If resistance is suspected or confirmed with recommended first-line antivirals, foscarnet is usually effective. However, its use is associated with a greater risk of serious... 

The use of trimethoprim-sulfamethoxazole in cancer patients at risk for P. jiwveci pneumonia has reduced the incidence of this protozoal infection substantially. Antiviral prophylaxis with acyclovir or newer agents (valacyclovir and famciclovir) is employed in most centers to reduce the risk of HSV reactivation in patients with acute leukemia undergoing intensive chemotherapy. Varicella vaccine provides good protection (90%) in leukemic children and also may be useful in seronegative adults, although the vaccine has been less well studied in this population. 

The Antiviral Activity of Ascorbic Acid. Some cancers are thought to be initiated by oncogenic viruses [see discussion by Oulbecco (106)], and this whole area is the focus of much current research interest, with proposals that antiviral agents be used in cancer prophylaxis and chemotherapy (208). Against this background the antiviral activity of ascorbic acid assumes fresh importance. 

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