W29 - Antivirals Flashcards
Herpesviruses 3 subfamilies?
- Alpha
- Beta
- Gamma
Members of herpesviruses subfamilies:
- Alpha?
- Beta?
- Gamma?
Members of herpesviruses subfamilies:
- Alpha = HSV-1, HSV-2, VZV
- Beta = CMV, HHV-6, HHV-7
- Gamma = EBV, HHV-8 (KSHV)
Which herpesvirus subfamily has latency in sensory ganglia?
Alpha (HSV-1, HSV2, VZV)
1 complication of chickenpox in adults? who is it more common in?
Varicella pneumonia (chickenpox pneumonitis)
- more common in those with lymphom or severely immunocompromised
Describe zoster in
A) immunocompetent
B) immunocompromised
Describe zoster in
A) immunocompetent = dermatomal distribution, complicated by post-herpetic neuralgia
B) immunocompromised = multidermatomal or disseminated infection (looks a bit like chickenpox)
4 typical advatnages of a prodrug
Generally:
- reduced toxicity
- increased efficacy
- longer half lives
- better bioavailability
First line antiviral drugs for HSV and VZV?
- Aciclovir (oral or IV)
- Valaciclovir (prodrug of aciclovir; oral)
acyclovir drug class & MOA
guanosine analogue => becomes incorporated into growing chain of DNA => blocks chain elongation b/c it lacks 3’OH
How is acyclovir specific for virally infected cells vs all human cells?
Initially, requires monophosphorylation by viral enzyme called thymidine kinase so this is found predominantly in cells affected by virus = only activated in virally infected cells = reduced drug toxicity
HSV encephalitis:
- treatment?
On clinical suspicion, start empirical treatment immediately with IV ACV 10mg/kg TDS (WITHOUT waiting for test result)
- if confirmed => continue for 14-21 d => recheck LP to ensure HSV -
In which groups of individuals (4) is VZV infections treated with aciclovir?
- Chickenpox in adults (due to risk of pneumonitis)
- Zoster in adults
- Immunocompromised - primary infection or re-activation
- Neonatal chickenpox
CMV latency in which cells?
Some monocyte and dentritic cell precursors
When does CMV become problematic?
In immunocompromised people, (HIV-AIDS), it can lead to opportunistic infections (interstitial CMV pneumonitis, CMV retinitis [owl’s eye retinitis])
Name 1st line, 2nd line, and 3rd line drugs for CMV infection
- Ganciclovir
1b. Valganciclovir (prodrug of GCV) - Foscarnet
- Cidofovir
How do ganciclovir (GCV) and valganciclovir (vGCV) exert their antiviral effects?
Mostly active against CMV.
guanosine analogue => phosphorylated by CMV viral UL97 kinase => inhibits viral DNA synthesis
Indications for use of Ganciclovir (GCV) and valganciclovir (vGCV)?
- CMV disease in immunocompromised (retinitis, pneumonitis)
- Neonates with congenital CMV
S/E (3) of (val/)Ganciclovir
Less tolerated than ACV
- Bone marrow toxicity (leukopenia, thrombocytopenia, anaemia, pancytopenia)
- Renal toxicity
- Hepatic toxicity
Foscarnet:
- MOA
- indications (3)
- S/E (1)
Foscarnet:
- MOA: non-compeitive inhibitor of viral DNA polymerase
- indications:
- CMV treatment in pre-engrftment post-BMT
- GCV-resistant CMV
- CMV retinitis
- S/E: nephrotoxic
Describe the following strategies for management of CMV in transplant patients:
- Treat
- Prophylaxis
- Pre-emptive therapy
Strategies for management of CMV in transplant patients:
- Treat = established disease then start ganciclovir and reduce immunosuppression => but this has HIGH mortlity rates!
- Prophylaxis = give GCV/vGCV - generally effective and mains trategy in solid organ transplants (i.e. renal).
- Pre-emptive therapy = minitoring, i.e. weekly or twice weekly for presence of ++ blood CMV PCR => treat if [viral] meets threshold. mostly used for stem cell transplant
Antiviral drug now licensed in the UK only for CMV prophylaxis in CMV IgG+ HSCT recipient patients is…
Letermovir
