Antiviral Agents

Question 1

Acyclovir

1) Mechanism of Action
2) Uses
3) Resistance

Answer 1

1) Nucleoside (Guanosine) Analog- inhibits viral synthesis by: binding to viral DNA polymerase causing polymerase inhibition and/or viral DNA chain termination after incorporation into viral DNA
* *Requires activation by viral Thymidine Kinase enzyme**
2) Long-term suppression of genital herpes (HSV-2), Varicella zoster virus (VZV) at higher doses
3) Usually only occurs in immunocompromised patients w/chronic use

Question 2

Valacyclovir

1) Mechanism of Action
2) Uses

Answer 2

1) Nucleoside (Guanosine) Analog- inhibits viral synthesis by: binding to viral DNA polymerase causing polymerase inhibition and/or viral DNA chain termination after incorporation into viral DNA
* *This is a Prodrug of acyclovir-requires activation by viral Thymidine Kinase enzyme**
2) Long-term suppression of genital herpes (HSV-2), Varicella zoster virus (VZV) at higher doses, Prevention of CMV w/organ transplantation

Question 3

Docosanol

1) Mechanism of Action
2) Use

Answer 3

1) Blocks fusion of viral and cellular membranes

2) Orolabial herpes ONLY (topical)

Question 4

Ganciclovir

1) Mechanism of Action
2) Uses
3) Resistance
4) Adverse Effect

Answer 4

1) Nucleoside Analog- inhibits viral synthesis by: binding to viral DNA polymerase causing polymerase inhibition and/or viral DNA chain termination after incorporation into viral DNA
* *Requires activation by CMV Kinase UL97**
2) CMV especially in advanced immunosuppression, CMV retinitis, along w/HSV, VZV, and EBV
3) Via mutation of CMV Kinase UL97 or viral DNA polymerase UL54(High level resistance!)
4) Myelosuppression

Question 5

Valganciclovir

1) Mechanism of Action
2) Uses

Answer 5

1) Nucleoside Analog- inhibits viral synthesis by: binding to viral DNA polymerase causing polymerase inhibition and/or viral DNA chain termination after incorporation into viral DNA
* *Prodrug of Ganciclovir-requires activation by CMV Kinase UL97**
2) CMV especially in advanced immunosuppression, CMV retinitis, along w/HSV, VZV, and EBV

Question 6

Abacavir

1) Mechanism of Action
2) Use
3) Resistance

Answer 6

1) Nucleoside/Nucleotide Reverse Transcriptase Inhibitor-inhibits viral Reverse Transcriptase (RT) causing chain termination/inhibition of viral DNA replication
2) HIV
* Combination therapy w/Lamivudine*
3) Multiple RT mutations required for resistance

Question 7

Lamivudine

1) Mechanism of Action
2) Use

Answer 7

1) Nucleoside/Nucleotide Reverse Transcriptase Inhibitor-inhibits viral Reverse Transcriptase (RT) causing chain termination/inhibition of viral DNA replication
2) HIV
* Combination therapy w/Abacavir*

Question 8

Efavirenz

1) Mechanism of Action
2) Use
3) Resistance
4) Adverse Effects

Answer 8

1) NON-nucleoside Reverse Transcriptase Inhibitors-allosteric inhibition of viral Reverse Transcriptase (RT)
* Does NOT complete w/nucleosides like NRTIs*
2) HIV
3) Resistance high Requires HIV genotyping
4) CNS Symptoms, Fetal abnormalities

Question 9

Nevirapine

1) Mechanism of Action
2) Use
3) Resistance
4) Adverse Effects

Answer 9

1) NON-nucleoside Reverse Transcriptase Inhibitors-allosteric inhibition of viral Reverse Transcriptase (RT)
* Does NOT complete w/nucleosides like NRTIs*
2) HIV, Prevention of HIV transmission from mother to newborn
3) Resistance high Requires HIV genotyping
4) CYP inducer-lowers methadone levels

Question 10

Ritonavir

1) Mechanism of Action
2) Use
3) Resistance

Answer 10

1) Antiretroviral Protease Inhibitor-inhibits viral Protease which inhibits cleavage of protein precursors leading to immature, noninfectious viral particles
2) HIV, PI “booster therapy”
* Enhancer of Saquinavir d/t CYP inhibitor effects*
3) Several mutations-requires genotyping

Question 11

Saquinavir

1) Mechanism of Action
2) Use
3) Resistance

Answer 11

1) Antiretroviral Protease Inhibitor-inhibits viral Protease which inhibits cleavage of protein precursors leading to immature, noninfectious viral particles
2) HIV, PI “booster therapy”
* Combination therapy w/Ritonavir*
3) Several mutations-requires genotyping

Question 12

Enfuvirtide

1) Mechanism of Action
2) Use

Answer 12

1) Antiretroviral Entry Inhibitor-inhibits the conformational change of virus by binding to the gp41 subunit of the viral envelope glycoprotein and INHIBITING FUSION of virus to host cell membrane
2) HIV
* Minimal adverse effects*

Question 13

Maraviroc

1) Mechanism of Action
2) Use

Answer 13

1) Antiretroviral Entry Inhibitor CCR5 Receptor Antagonist-binds to host cell protein CCR5 to inhibit binding of virus to host cell membrane
2) CCR5-tropic HIV-1 infection after virologic failure d/t resistance of other therapies

Question 14

Dolutegravir

1) Mechanism of Action
2) Use

Answer 14

1) Antiretroviral Integrase Inhibitor-inhibits viral Integrase enzyme blocking integration of proviral DNA into host genome
2) HIV