Antivirals

Question 1

MOA:
Monophosphorylated by viral thymidine kinase (TK), then further
bioactivated by host-cell kinases to the triphosphate
– Acyclovir-triphosphate is both a substrate for and inhibitor of viral
DNA polymerase
– When incorporated into the DNA molecule, acts as a chain termina-
tor because it lacks the equivalent of a ribosyl 3′ hydroxyl group

Answer 1

Acyclovir

Question 2

Tx for HSV, VZV

Answer 2

Acyclovir

Question 3

MOA:
Similar to that of acyclovir
– First phosphorylation step is viral-specific; involves thymidine kinase in HSV and a phosphotransferase (UL97) in cytomegalovirus (CMV)
– Triphosphate form inhibits viral DNA polymerase and causes chain termination

Answer 3

Ganciclovir

Question 4

Tx for HSV, VZV, and CMV

S/E:
dose-limiting hematotoxicity (leukopenia, thrombo- cytopenia), mucositis, fever, rash, crystalluria (maintain hydration); seizures in overdose

Answer 4

Ganciclovir

Question 5

MOA:
Not an antimetabolite, but still inhibits viral DNA and RNA polymerases
– Uses identical to ganciclovir, plus > activity versus acyclovir- resistant strains of HSV

Answer 5

Foscarnet

Question 6

MOA:
Phosphorylated nonspecifically to a triphosphate that can inhibit reverse transcriptase (RT) by competing with natural nucleotides and can also be incorporated into viral DNA to cause chain termination.
– Resistance occurs by mutations (multiple) in the gene that codes for RT.

Answer 6

Zidovudine (Azidothymidine, ZDV, AZT)

Question 7

– Are components of most combination drug regimens used in
HIV infection
– Are used together with a protease inhibitor (PI)
– Highly active antiretroviral therapy (HAART) has often resulted in ↓ viral RNA, reversal of the decline in CD4 cells, and ↓ opportunistic infections

Answer 7

Nucleoside reverse transcriptase inhibitors (NRTIs):

Question 8

MOA:
– RTIs that do not require metabolic activation: nevirapine, efavirenz
– Are not myelosuppressant
– Inhibit reverse transcriptase at a site different from the one NRTIs bind to
– Additive or synergistic if used in combination with NRTIs and/or PIs

Answer 8

Nonnucleoside reverse transcriptase inhibitors (NNRTIs):

Question 9

NtRTI that has a single phosphate on its sugar residue and must be further phosphorylated to the triphosphate form.

Answer 9

Tenofovir