Antivirals

Question 1

What are viruses?

Answer 1

Obligate intracellular parasites

Question 2

What do viruses require to replicate?

Answer 2

The utilisation of host cell enzymes

Question 3

What is an example of an adverse effect of an antiviral?

Answer 3

Mitochondrial toxicity

Question 4

What are most antivirals?

Answer 4

Nucleoside analogues –> Inhibit nucleic acid synthesis

Question 5

Which antivirals target receptor binding?

Answer 5

Docosonal (Herpes)

Question 6

Which antivirals target cell entry?

Answer 6

Chemokine-receptor blocking agents-(HIV)

Question 7

Which antivirals target uncoating?

Answer 7

• Amantidine
• Rimantidine

For Influenza A

Question 8

Which antivirals target nucleic acid synthesis?

Answer 8

1) Nucleoside analogues
- Acyclovir (HSV, VSV)
- Ganciclovir (CMV)

2) Viral DNA polymerase inhibitors:
- Cidofovir (HSV, CMV)
- Foscarnet (HSV, CMV)

3) Guanine nucleotide synthesis:
- Ribvirin (RSV, HCV)

Question 9

Which antivirals target Reverse transcriptase?

Answer 9

1) Non-nucleoside reverse transcriptase inhibitors (HIV):
- Delaviridine
- Efavirenz
- Nevirapine

2) Nucleotide reverse transcriptase inhibitors

Question 10

Which antivirals target DNA integration?

Answer 10

Integrase inhibitors (HIV):

• Dolutegravir
• Elvitegravir
• Raltegravir

“…egravir”

Question 11

Which antivirals target the release of progeny virus (Influenza A and B)?

Answer 11

Neuraminidase inhibitors:

• Osteltamivir
• Zanamivir

Question 12

Which antivirals target proteolytic processing?

Answer 12

Protease inhibitors (HIV):

• Atazanavir
• Darunavir
• Indinavir

”..navir”

Question 13

When may we use antivirals?

Answer 13

• Prophylaxis
• Pre-emptive therapy
• Overt disease
• Suppressive therapy

Question 14

Why is Prophylaxis used?

Answer 14

To prevent infection

Question 15

Why is Pre-emptive therapy used in viral infection?

Answer 15

When evidence of infection is detected, but before symptoms apparent

Question 16

Why is suppressive therapy used in viral infection?

Answer 16

To keep viral replication below the rate that causes tissue damage in asymptomatic infected patient

Question 17

Examples of Antivirals used in overt disease?

Answer 17

Nucleoside analogues:

• Aciclovir
• HSV and VSV
• “…clovir”

Neuraminidase inhibitors:

• Oseltamivir
• Influenza A and B
• “…amivir”

Question 18

Examples of Antivirals used in pre-emptve viral infection?

Answer 18

Protein synthesis:
- Interferon-a = HBV and HCV

Nucleotide analogue:
- Ribavirin = RSV and HCV

Question 19

Examples of Antivirals used in suppressive viral infection?

Answer 19

Antiretroviral (HIV) therapy:

• Attachment inhibitor (Maraviroc)
• Penetration inhibitors (Enfuvirtide)
• NRTI
• NNRTIs
• Integrase inhibitors
• Protease inhibitors

Question 20

Examples of Antivirals used in prophylaxis?

Answer 20

Acyclovir a nucleoside analogue for herpes (HSV)

Question 21

What are antivirals role in latently infected cells e.g. herpes virus?

Answer 21

1) They can treat over infection
2) They do not eradicate virus
3) Suppression is then used to reduce risk overt infection

Question 22

Antivirals for herpes viruses, HSV 1 and 2?

Answer 22

HSV:
- Nucleoside analogues e.g. acyclovir “…clovir”

• Viral DNA polymerase inhibitors e.g. Cidofovir or Foscarnet

Question 23

Antivirals for herpes viruses, VZV?

Answer 23

Nucleoside analogues e.g. acyclovir “…clovir”

Question 24

Antivirals for herpes viruses, CMV?

Answer 24

• Nucleoside analogues e.g. Ganciclovir “…clovir”

- Viral DNA polymerase inhibitors e.g. Cidofovir or Foscarnet

Question 25

Antivirals for Hepatits B and C?

Answer 25

- Nucleotide reverse transcriptase inhibitors, e.g. Tenofovir - Protein synthesis inhibitor, e.g. Interferon-a Nucleotide analogues, HCV: Ribavirin

Question 26

Antivirals in influenza?

Answer 26

Neuraminidase inhibitors: - Oseltamivir - Zanamivir

Question 27

Antivirals in respiratory syncytial virus, RSV?

Answer 27

Nucleotide analogue: | - Ribavirin

Question 28

When are antivirals used in herpes simplex HSV, e.g. Acyclovir, cidofovir or foscarnet?

Answer 28

- Mucocutaneous: Oral, genital, eye, skin - Encephalitis - Immunocompromised, any site

Question 29

When are antivirals used in chicken pox, VZV?

Answer 29

In this at increased risk of complications: - Neonate - Immunocomprimised - Pregnant

Question 30

When are antivirals used in shingles, VZV?

Answer 30

Immunocompetent host but only if begun within 72 hours of onset of symptoms

Question 31

How is the nucleoside analogue, acyclovir, administered (HSV, VZV)?

Answer 31

- Oral - Intravenous - Eye ointment - Topical cream

Question 32

How is the nucleoside analogue, valaciclovir, administered (HSV, VZV)?

Answer 32

Oral

Question 33

How is the nucleoside analogue, famciclovir, administered (HSV, VZV)?

Answer 33

Oral

Question 34

How is the viral DNA polymerase inhibitor, foscarnet, administered (HSV, VZV)?

Answer 34

Intravenous

Question 35

What is the mode of action of nucleoside analogues (HSV, VZV, CMV)?

Answer 35

1) Acyclovir is monophosphorylated by HSV/VZV thymidine kinase to Acyclovir monophosphate, ACVMP 2) ACVMP is further phosphorylate by hosts kinase enzymes in infected cells to acyclovir triphosphate, ACVTP 3) ACVTP, competitively inhibits and inactivates HSV-specific DNA polymerase 4) Viral DNA synthesis inhibited

Question 36

Why does acyclovir few adverse effect, low cellular toxicity?

Answer 36

1) Initial phosphorylation only takes place in viral infected cells 2) Acyclovir triphosphate inhibits viral, not cellular, DNA polymerase

Question 37

Antivirals used in CMV?

Answer 37

Nucleoside analogues: - Ganciclovir - Valganciclovir Viral DNA polymerase inhibitors: - Cidofovir - Foscaret

Question 38

How is ganciclovir administered in CMV?

Answer 38

Ganciclovir, a nucleoside analogue is administered by: - Intravenous - Ocular implant

Question 39

How is valganciclovir administered in CMV?

Answer 39

Valganciclovir, a nucleoside analogue is administered by: | - Oral route

Question 40

How is cidofovir administered in CMV?

Answer 40

Cidofovir, a viral DNA polymerase inhibitor, is administered: - Intravenously

Question 41

How is foscarnet administered in CMV?

Answer 41

Foscarnet, a viral DNA polymerase inhibitor, is administered: - Intravenously

Question 42

When are antivirals used in CMV?

Answer 42

1) In life or sight-threatening CMV infections: - HIV patients within CMV retinitis or colitis - Transplant recipients = pneumonitis 2) Neonates with symptomatic congenital CMV infection

Question 43

What is the therapy protocol called in HIV therapy?

Answer 43

Combination anti-retroviral therapy, cART Also known as, Highly active antiretroviral therapy, HAART

Question 44

Antivirals for chronic hepatitis B?

Answer 44

Nucleoside/tide analogues: - Tenofovir - Adefovir - Entecavir - Lamivudine - Emtricitabine - Telbivudine Interferon-a

Question 45

Antivirals for chronic hepatits C?

Answer 45

Often 12-48 weeks Current: - Interferon-a - Guanine nucleotide analogue, Ribavirin (Oral) - Protease inhibitors, telaprevir or boceprevir New: - Daclatasvir - Sofosbuvir - Simeprevir

Question 46

How can you test antiviral resistance?

Answer 46

1) Phenotypic - Can virus from in presence of the compound e.g. HSV 2) Genotypic - Sequence genome and identify resistance associated mutation e.g. HIV

Question 47

When would you suspect antiviral resistance in herpes in immunocompromised?

Answer 47

If there is no response to appropriate antiviral within 7 days Examples - Acyclovir, cidofovir, foscarnet

Question 48

If HSV or CMV is resistant to acyclovir what is the next therapeutic option usually?

Answer 48

Foscarnet, a viral DNA polymerase inhibitor

Question 49

When would trough and peaks need to be monitored in acyclovir therapy?

Answer 49

For patients with renal impairment