Antivirals Flashcards
Which viruses does acyclovir treat?
HSV, VZV, EBV
How does acyclovir work?
Activated by viral thymidine kinase. Once activated, can block viral DNA extension by competitively inhibiting viral DNA polymerases
What is acyclovir an analogue for?
Guanosine
Why is acyclovir not an effective treatment for CMV?
CMV lacks the thymidine kinase enzyme
Which viruses does gangciclovir treat?
CMV, EBV, HHV-6
What is a side effect of ganciclovir?
Bone marrow suppression
Who requires treatment for CMV?
Neonates (congenital)
Immunocompromised
Pregnancy
HIV
RCHEP is a mnemonic for the effects of CMV. What does it stand for?
Retinitis Colitis Hepatitis Encephalitis Pneumonitis
What do cells infected with CMV show on microscopy?
Owl’s eye inclusions
If resistant/allergic/sever side effects to ganciclovir, which 2 antivirals can be used instead?
Foscarnet
Cidofovir
What is foscarnet an analogue of?
Pyrophosphonate
How does foscarnet work?
Inhibits nucleic acid synthesis without requiring activation
Also used as prophylaxis post organ transplant
What are the main uses of cidofovir?
Treating CMV retinitis (esp in HIV pts)
Treatment of non-herpes viral infections in opportunistic post-transplant setting (eg BK virus, adenovirus, JC virus)
How does cidofovir work?
Inhibits viral replication by selectively inhibiting viral DNA polymerases
Also incorporates itself into viral DNA hence inhibiting viral DNA synthesis during reproduction
Which organ do foscarnet and cidofovir cause toxicity to, and how is this side effect mitigated?
Nephrotoxic
Maintain hydration and co-administer probenecid
The mnemonic for HSV (genital, oral, encephalitis, disseminated) treatment is Act Very Fast, what does this stand for?
Acyclovir
Valaciclovir
Famciclovir
In a serious HSV infection what should be stared as early as possible?
IV acyclovir
What is the treatment for a serious HSV infection + ganciclovir resistance?
Foscarnet/cidofovir
In which pts does VZV require treatment?
Immunocompromised
Pregnant
Adults with pneumonitis
What is the preemptive therapy for CMV in bone marrow transplants?
Monitor CMV viral load in the blood during high risk period
What is the acute therapy for CMV in bone marrow transplants?
1st line: ganciclovir (but has marrow toxicity!)
2nd line: foscarnet (nephrotoxic) / ganciclovir+foscarnet combo
3rd line: cidofovir (nephrotoxic)
What are the 3 criteria for deciding when to treat hep B (HBV)?
1) Serum HBV DNA levels (>2000IU/ml)
2) Serum aminotransferase (ALT, AST) levels (>normal upper limit)
3) Liver biopsy histological grade + stage: moderate-severe active necroinflammation and/or fibrosis
What are the treatment goals when treating Hep B?
- Prevent progression to cirrhosis and hepatocellular carcinoma (HCC)
- Maintain serum HBV DNA level as low as possible
- Attain histology improvement
- ALT normalisation
- Loss of HBVeAg and seroconversion to HBVeAb
One treatment option for HBV is pegylated interferon (INF) alpha 2a. How is this administered?
Subcut
What are the 2 modes of action of pegylated interferon (INF) alpha 2a?
Direct antiviral effect
Upregulates expression of MHC on cell surfaces
HBV can also be treated with nucleoside and nucleotide analogues. What are the 2 groups of these drugs?
Inhibitors of viral polymerase
Inhibitors of reverse transcriptase
List 4 inhibitors of viral polymerase, used in the treatment of HBV
Lamivudine
Adefovir dipivoxil
Entecavir (no resistance)
Telbivudine
Name an inhibitor of reverse transcriptase used in the treatment of HBV
Tenofovir
What is the preferred 1st line treatment combination for HBV?
Entecavir AND PegINF alpha 2a AND Tenofovir
What are the treatment goals when treating Hep C (HCV)?
- Sustained virologic response (SVR): persistant absence of HCV RNA in serum >6/12 after completing antiviral treatment
- Prevent progression to cirrhosis / HCC / decompensated liver disease requiring liver transplantation
What is the treatment for HCV?
Combination of:
- PegINF alpha 2a/2b
- Ribavirin (RNA nucleoside analogue)
What is the major side effect of ribivirin?
Haemolytic anaemia
How many distinct genotypes of HCV are there and why is this clinically significant?
6 - genotype predicts response to treatment
In which HCV genotypes is treatment more successful?
2 and 3 (~50% of UK burden)
In which HCV genotypes is treatment less successful?
1, 4, 5 and 6 (~50% of UK burden)
How are respiratory viruses diagnosed?
PCR-BAL
Throat swab
Nasopharyngeal aspirate (NPA)
Which treatments are used for influenza and what is their route of administration?
Zanamivir (inhaled)
Oseltamivir (PO)
Amantadine (PO)
What is the treatment for respiratory syncitial virus (RSV) /parainfluenza?
Ribavirin (guanosine analogue)
