Antivirals Flashcards
What are viruses?
Obligate intracellular parasites
What do viruses require to replicate?
The utilisation of host cell enzymes
What is an example of an adverse effect of an antiviral?
Mitochondrial toxicity
What are most antivirals?
Nucleoside analogues –> Inhibit nucleic acid synthesis
Which antivirals target receptor binding?
Docosonal (Herpes)
Which antivirals target cell entry?
Chemokine-receptor blocking agents-(HIV)
Which antivirals target uncoating?
- Amantidine
- Rimantidine
For Influenza A
Which antivirals target nucleic acid synthesis?
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)
Which antivirals target Reverse transcriptase?
1) Non-nucleoside reverse transcriptase inhibitors (HIV):
- Delaviridine
- Efavirenz
- Nevirapine
2) Nucleotide reverse transcriptase inhibitors
Which antivirals target DNA integration?
Integrase inhibitors (HIV):
- Dolutegravir
- Elvitegravir
- Raltegravir
“…egravir”
Which antivirals target the release of progeny virus (Influenza A and B)?
Neuraminidase inhibitors:
- Osteltamivir
- Zanamivir
Which antivirals target proteolytic processing?
Protease inhibitors (HIV):
- Atazanavir
- Darunavir
- Indinavir
”..navir”
When may we use antivirals?
- Prophylaxis
- Pre-emptive therapy
- Overt disease
- Suppressive therapy
Why is Prophylaxis used?
To prevent infection
Why is Pre-emptive therapy used in viral infection?
When evidence of infection is detected, but before symptoms apparent
Why is suppressive therapy used in viral infection?
To keep viral replication below the rate that causes tissue damage in asymptomatic infected patient
Examples of Antivirals used in overt disease?
Nucleoside analogues:
- Aciclovir
- HSV and VSV
- “…clovir”
Neuraminidase inhibitors:
- Oseltamivir
- Influenza A and B
- “…amivir”
Examples of Antivirals used in pre-emptve viral infection?
Protein synthesis:
- Interferon-a = HBV and HCV
Nucleotide analogue:
- Ribavirin = RSV and HCV
Examples of Antivirals used in suppressive viral infection?
Antiretroviral (HIV) therapy:
- Attachment inhibitor (Maraviroc)
- Penetration inhibitors (Enfuvirtide)
- NRTI
- NNRTIs
- Integrase inhibitors
- Protease inhibitors
Examples of Antivirals used in prophylaxis?
Acyclovir a nucleoside analogue for herpes (HSV)
What are antivirals role in latently infected cells e.g. herpes virus?
1) They can treat over infection
2) They do not eradicate virus
3) Suppression is then used to reduce risk overt infection
Antivirals for herpes viruses, HSV 1 and 2?
HSV:
- Nucleoside analogues e.g. acyclovir “…clovir”
- Viral DNA polymerase inhibitors e.g. Cidofovir or Foscarnet
Antivirals for herpes viruses, VZV?
Nucleoside analogues e.g. acyclovir “…clovir”
Antivirals for herpes viruses, CMV?
- Nucleoside analogues e.g. Ganciclovir “…clovir”
- Viral DNA polymerase inhibitors e.g. Cidofovir or Foscarnet
Antivirals for Hepatits B and C?
- Nucleotide reverse transcriptase inhibitors, e.g. Tenofovir
- Protein synthesis inhibitor, e.g. Interferon-a
Nucleotide analogues, HCV:
Ribavirin
Antivirals in influenza?
Neuraminidase inhibitors:
- Oseltamivir
- Zanamivir
Antivirals in respiratory syncytial virus, RSV?
Nucleotide analogue:
- Ribavirin
When are antivirals used in herpes simplex HSV, e.g. Acyclovir, cidofovir or foscarnet?
- Mucocutaneous: Oral, genital, eye, skin
- Encephalitis
- Immunocompromised, any site
When are antivirals used in chicken pox, VZV?
In this at increased risk of complications:
- Neonate
- Immunocomprimised
- Pregnant
When are antivirals used in shingles, VZV?
Immunocompetent host but only if begun within 72 hours of onset of symptoms
How is the nucleoside analogue, acyclovir, administered (HSV, VZV)?
- Oral
- Intravenous
- Eye ointment
- Topical cream
How is the nucleoside analogue, valaciclovir, administered (HSV, VZV)?
Oral
How is the nucleoside analogue, famciclovir, administered (HSV, VZV)?
Oral
How is the viral DNA polymerase inhibitor, foscarnet, administered (HSV, VZV)?
Intravenous
What is the mode of action of nucleoside analogues (HSV, VZV, CMV)?
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
Why does acyclovir few adverse effect, low cellular toxicity?
1) Initial phosphorylation only takes place in viral infected cells
2) Acyclovir triphosphate inhibits viral, not cellular, DNA polymerase
Antivirals used in CMV?
Nucleoside analogues:
- Ganciclovir
- Valganciclovir
Viral DNA polymerase inhibitors:
- Cidofovir
- Foscaret
How is ganciclovir administered in CMV?
Ganciclovir, a nucleoside analogue is administered by:
- Intravenous
- Ocular implant
How is valganciclovir administered in CMV?
Valganciclovir, a nucleoside analogue is administered by:
- Oral route
How is cidofovir administered in CMV?
Cidofovir, a viral DNA polymerase inhibitor, is administered:
- Intravenously
How is foscarnet administered in CMV?
Foscarnet, a viral DNA polymerase inhibitor, is administered:
- Intravenously
When are antivirals used in CMV?
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
What is the therapy protocol called in HIV therapy?
Combination anti-retroviral therapy, cART
Also known as,
Highly active antiretroviral therapy, HAART
Antivirals for chronic hepatitis B?
Nucleoside/tide analogues:
- Tenofovir
- Adefovir
- Entecavir
- Lamivudine
- Emtricitabine
- Telbivudine
Interferon-a
Antivirals for chronic hepatits C?
Often 12-48 weeks
Current:
- Interferon-a
- Guanine nucleotide analogue, Ribavirin (Oral)
- Protease inhibitors, telaprevir or boceprevir
New:
- Daclatasvir
- Sofosbuvir
- Simeprevir
How can you test antiviral resistance?
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
When would you suspect antiviral resistance in herpes in immunocompromised?
If there is no response to appropriate antiviral within 7 days
Examples - Acyclovir, cidofovir, foscarnet
If HSV or CMV is resistant to acyclovir what is the next therapeutic option usually?
Foscarnet, a viral DNA polymerase inhibitor
When would trough and peaks need to be monitored in acyclovir therapy?
For patients with renal impairment
