Herpes

Question 1

Acyclovir

Answer 1

Competitive inhibitor of viral DNA polymerase and causes DNA chain termination when incorporated into primer strand

Low oral bioavailability (10-30%)

Resistance through changes in viral thymidine kinase (most common) or altered viral DNA poly.

Treatment of VZV and HSV-1 and -2.

Well tolerated

Question 2

Valacyclovir

Answer 2

Competitive inhibitor of viral DNA polymerase and causes DNA chain termination when incorporated into primer strand

High oral bioavailability (70%)

Resistance through changes in viral thymidine kinase (most common) or altered viral DNA poly.

Treatment of VZV and HSV-1 and -2.

Well tolerated

Question 3

Penciclovir

Answer 3

Low oral bioavailability (5%)

Competitive inhibition of viral DNA polymerase

Resistance through thymidine kinase deficient viruses

Well tolerated

Treatment of VZV and HSV-1 and -2.

Question 4

Famciclovir

Answer 4

High oral bioavailability (65-77%)

Competitive inhibition of viral DNA polymerase

Resistance through thymidine kinase deficient viruses

Well tolerated

Treatment of VZV and HSV-1 and -2, mostly HIV patients with HSV mucocutaneous infection.

Question 5

Ganciclovir

Answer 5

Guanine nucleoside analog, inhibits deoxyguanosine triphosphate incorporation into DNA and inhibits viral DNA polymerase

Resistance through mutant viral phosphotransferase or viral DNA polymerase

Low oral bioavailability (6-9%)

Especially effective against CMV, works for HSV as well

Neutropenia
Thrombocytopenia
Teratogenic in animals

Question 6

Valganciclovir

Answer 6

Guanine nucleoside analog, inhibits deoxyguanosine triphosphate incorporation into DNA and inhibits viral DNA polymerase

Resistance through mutant viral phosphotransferase or viral DNA polymerase

High oral bioavailability (61%)

Especially effective against CMV, works for HSV as well

Neutropenia
Thrombocytopenia
Teratogenic in animals

Question 7

Cidofovir

Answer 7

Inhibits viral DNA synthesis (false metabolite) – Does not rely on viral phosphorylation like other treatments

Resistance through mutations in viral DNA polymerase

Treatment of CMV infection, also active against HSV, papilloma, polyoma, pox, and adenoviruses

Nephrotoxicity
Neutropenia
Rat carcinogen

Question 8

Foscarnet

Answer 8

Mimics PPi, inhibits viral DNA polymerase at the PPi binding site

Resistance through mutations in viral DNA polymerase

Treatment of CMV retinitis (AIDS patients) and acyclovir-resistant HSV and VZV

Renal impairment - hypocalcemia (prevent with hydration)

Question 9

Idoxuridine

Answer 9

Incorporated in viral and cellular DNA, inhibiting synthesis

Topical treatment of HSV keratitis and poxviruses

Question 10

Trifluridine

Answer 10

Inhibition of viral DNA polymerase, intermediate product (monophosphate) inhibits thymidylate synthase

Treatment of primary keratoconjunctivitis and recurrent epithelial keratitis (HSV)

Systemic toxicity

Question 11

Vidarabine

Answer 11

Purine nucleoside analog, inhibition of viral DNA polymerase

Treatment of HSV, VZV, EBV

Question 12

Docosanol

Answer 12

OTC treatment of orolabial herpes

Inhibits in vitro replication of lipid-enveloped viruses

For HSV, inhibits viral entry into cell (ie. cannot spread to surrounding, healthy cells)

Question 13

Fomivirsen

Answer 13

Blocks translation of viral mRNA through sequence-specific mechanisms targeting the immediate-early transcriptional region of CMV