Antivirals

Question 1

DNA Nucleoside Analogues

Answer 1

Mech: Selectively toxic due to high phosphorylation rate of viral thymidine kinase. Thymidine kinase phosphorylates drug which activates it (changes nucleoside into nucleotide).

Acyclovir
Valacyclovir (prodrug, avoid in SSRI pts)
Famcyclovir (prodrug, avoid in SSRI pts)

Question 2

Viral Fusion Inhibitors

Answer 2

Mech: Inhibits fusion between human cell membrane and viral envelope.

n-docosanol (Abreva)

Question 3

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Answer 3

Mech: Nucleoside analogues are phosphorylated by host cell thymidine kinase to nucleotides which are then incorporated during the reverse transcription process. Their integration onto the growing strand(s) inhibits further strand growth.

2 NRTIs always taken together (Backbone of therapy)

Tenofovir
Emtricitabine
Abacavir
Lamivudine
Zidovudine

Question 4

Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Answer 4

Mech: Directly block the reverse transcriptase enzyme.

Highest incidence of resistance at 18%

Nevirapine
Efavirenz
Rilpivirine
Doravirine

Question 5

Protease Inhibitors (PIs)

Answer 5

Mech: Block protein production and HIV viral assembly.

Strong CYP 3A4 Inhibitors (Increase concentration of other PIs or NNRTIs)
Adverse lipid effects: Increase TG, Lipodystrophy, Hypergylcemia.

"-navirs"
Ritonavir
Cobisistat
Atazanavir
Duranavir

Question 6

Integrase Strand Transfer Inhibitors (ISTIs)

Answer 6

Mech: block viral DNA integration into host cell DNA.

Preferred for initial treatment. High efficacy, low side effect profile, and minimal drug interactions. Often combined with 2 NRTIs as combination therapy is very common in anti-retroviral therapy)

"-gravirs"
Raltegravir
Dolutegravir
Elvitegravir
Bictegravir

Question 7

Single Tablet Regimens (Antiretroviral Therapy)

Answer 7

Biktarvy QD- Bictegravir/tenofovir alafenamide/emtricitabine. (ISTI + 2 NRTIs)

Triumeq- dolutegravir, abacavir, lamivudine. (ISTI + 2 NRTIs)

Question 8

Neuraminidase Inhibitors (Influenza A and B)

Answer 8

Mech: Binds the surface antigen neuraminidase on influenza A and B viruses and prevents the release of new virus from the host cell.

“-amivirs”

Oseltamivir (Tamiflu)
Zanamivir (Relenza)
Peramivir (IV only for uncomplicated influenza)

Question 9

Endonuclease Inhibitors (Influenza A and B)

Answer 9

Mech: Inhibits/blocks endonuclease activity that normally “uncoats” viral RNA. This prevents replication and transcription of the viral RNA.

Baloxavir marboxil (Xofluza)

Causes mutations in influenza by a rate of 10-20%. Escape mutant creation prolongs and increases severity of symptoms.

Not recommended for pregnant women, breastfeeding mothers, outpatients with complicated or progressive illness, or hospitalized patients because there
is no information about use of baloxavir in these patients.