34 Attacking the enemy: antivirals Flashcards
Antiviral drugs do not kill viruses, but stop viral replication. Monitor progress with therapeutic drug level monitoring, and viral loads.
Replication pathways if DNA viruses, RNA viruses and retroviruses differ upon entering host cell, so different antivirals attack different targets.
Antivirals difficult to classify, so often classified by disease they treat e.g anti-HIV
Where do different viruses replicate?
DNA viruses - nucleus e.g CMV, HBV, HPB, HSV, VSV
Retro viruses - nucleus e.g HIV, HTLV
RNA virus - cytoplasm. e.g HCV, RSV, influenza
How do these classes of anti-virals work?
1 5-substituted 2’-deoxyuridines
2 Nucleoside analogues
3 pyrophosphate analogues
1 5-substituted 2’-deoxyuridines - inhibit viral DNA synthesis in nucleus
2 Nucleoside analogues - inhibit viral DNA synthesis in nucleus, inhibit viral reverse transcriptase
3 pyrophosphate analogues - inhibit viral DNA synthesis in nucleus
How do these classes of anti-virals work?
4 NRTIs
5 NNRTIs
6 Protease inhibitor
4 NRTIs - inhibit reverse transcriptase in cytoplasm
5 NNRTIs - inhibit reverse transcriptase in cytoplasm
6 Protease inhibitor - inhibits viral protease, preventing protein formation, and viral maturation
How do these classes of anti-virals work?
7 Integrase inhibitor
8 entry inhibitor
9 acyclic guanosine analogues
7 Integrase inhibitor - inhibit viral integration of DNA in host DNA
8 entry inhibitor - prevent entry of virion (endocytosis)
9 acyclic guanosine analogues - inhibit viral DNA synthesis in nucleus
How do these classes of anti-virals work?
10 acyclic nuceloside phosphonate analogues (2)
11 HCV NS5A/ NS5G polymerase inhibitor
12 influenza virus inhibitors
10 acyclic nuceloside phosphonate analogues - inhibit viral DNA synthesis in nucleus, - inhibit reverse transcriptase in cytoplasm
11 HCV NS5A/ NS5G polymerase inhibitor - inhibit viral polymerase
12 influenza virus inhibitors - prevent viral uncoating, prevent exocytosis, inhibit viral polymerase
What are examples of drugs that target DNA viruses?
CMV -
Ganciclovir
Valganciclovir
Foscarnet
HSV/ VZV -
Aciclovir
Ganciclovir
Foscarnet
HBV - Emtrictabine Lamivudine Tenofovir INF alpha
What are examples of drugs which target RNA viruses?
Influenza A + B
Influenza A
RSV
Influenza A + B - oseltamivir, zanamavir
Influenza A - amantadine, rimantadine
RSV - ribavirin
Which broad classes target HIV?
NRTIs NNRTIs Fusion inhibitor CCR5 inhibitor Integrase inhibitors Protease inhibitor
HIV treatment. What are examples which belong to these classes?
NRTIs
Abacivir Emtricitabine Lamivudine (3TC) Stavudine (d4T) Tenofovir Zidovudine (AZT)
HIV treatment. What are examples which belong to these classes?
NNRTIs
Efavirenz
Nevirapine
Rilpivirine
HIV treatment. What are examples which belong to these classes?
Fusion inhibitor
CCR5 inhibitor
Fusion inhibitor -
Enfuvirtide (T20)
CCR5 inhibitor -
MAraviroc
HIV treatment. What are examples which belong to these classes?
Integrase inhibitors
Dolutegravir
Raltegravir
HIV treatment. What are examples which belong to these classes?
Protease inhibitors
Atazanavir
Indinavir
Lopinavir + ritonavir (kaletra)
HCV is RNA virus. Treatment with NS3 protease inhibitor, and NS5 polymerase inhibitors.
What are examples of NS3 protease inhibitor?
Simeprivir
Telaprivir
HCV is RNA virus. Treatment with NS3 protease inhibitor, and NS5 polymerase inhibitors.
What are examples of NS5 polymerase inhibitor?
Sofosbuvir
Ribavirin
IFN alpha
What are examples of drugs that target viral DNA polymerase?
Aciclovir Valaciclovir Famciclovir Ganciclovir Valganciclovir
What is mechanism of action of aciclovir?
Enters as prodrug - inactive
Phosphorylated by enzyme thymidine kinase carried only by HSV/ VZV, and the monophosphate is converted by cellular kinases to the triphosphate.
This acts as false substrate causing chain termination. It has higher affinity for viral polymerase than host polymerase.
Thymidine kinase only present in infected cells, so aciclovir only targets infected cells
Oral bioavailability aciclovir is 20%, so often given IV
What are sides effects of aciclovir
Excreted renally
Can crystallise in renal tract, and cause acute tubular necrosis
Ganciclovir has similar mechanism of aciclovir
What are benefits?
What are draw backs?
Wider range of action - also effective CMV DNA polymerase
Selective toxicity not seen, so can cause myelosuppression