W29 - Antivirals Flashcards

1
Q

Herpesviruses 3 subfamilies?

A
  1. Alpha
  2. Beta
  3. Gamma
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2
Q

Members of herpesviruses subfamilies:

  • Alpha?
  • Beta?
  • Gamma?
A

Members of herpesviruses subfamilies:

  • Alpha = HSV-1, HSV-2, VZV
  • Beta = CMV, HHV-6, HHV-7
  • Gamma = EBV, HHV-8 (KSHV)
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3
Q

Which herpesvirus subfamily has latency in sensory ganglia?

A

Alpha (HSV-1, HSV2, VZV)

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4
Q

1 complication of chickenpox in adults? who is it more common in?

A

Varicella pneumonia (chickenpox pneumonitis)

  • more common in those with lymphom or severely immunocompromised
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5
Q

Describe zoster in

A) immunocompetent

B) immunocompromised

A

Describe zoster in

A) immunocompetent = dermatomal distribution, complicated by post-herpetic neuralgia

B) immunocompromised = multidermatomal or disseminated infection (looks a bit like chickenpox)

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6
Q

4 typical advatnages of a prodrug

A

Generally:

  1. reduced toxicity
  2. increased efficacy
  3. longer half lives
  4. better bioavailability
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7
Q

First line antiviral drugs for HSV and VZV?

A
  1. Aciclovir (oral or IV)
  2. Valaciclovir (prodrug of aciclovir; oral)
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8
Q

acyclovir drug class & MOA

A

guanosine analogue => becomes incorporated into growing chain of DNA => blocks chain elongation b/c it lacks 3’OH

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9
Q

How is acyclovir specific for virally infected cells vs all human cells?

A

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

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10
Q

HSV encephalitis:

  • treatment?
A

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 -
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11
Q

In which groups of individuals (4) is VZV infections treated with aciclovir?

A
  1. Chickenpox in adults (due to risk of pneumonitis)
  2. Zoster in adults
  3. Immunocompromised - primary infection or re-activation
  4. Neonatal chickenpox
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12
Q

CMV latency in which cells?

A

Some monocyte and dentritic cell precursors

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13
Q

When does CMV become problematic?

A

In immunocompromised people, (HIV-AIDS), it can lead to opportunistic infections (interstitial CMV pneumonitis, CMV retinitis [owl’s eye retinitis])

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14
Q

Name 1st line, 2nd line, and 3rd line drugs for CMV infection

A
  1. Ganciclovir
    1b. Valganciclovir (prodrug of GCV)
  2. Foscarnet
  3. Cidofovir
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15
Q

How do ganciclovir (GCV) and valganciclovir (vGCV) exert their antiviral effects?

A

Mostly active against CMV.

guanosine analogue => phosphorylated by CMV viral UL97 kinase => inhibits viral DNA synthesis

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16
Q

Indications for use of Ganciclovir (GCV) and valganciclovir (vGCV)?

A
  1. CMV disease in immunocompromised (retinitis, pneumonitis)
  2. Neonates with congenital CMV
17
Q

S/E (3) of (val/)Ganciclovir

A

Less tolerated than ACV

  1. Bone marrow toxicity (leukopenia, thrombocytopenia, anaemia, pancytopenia)
  2. Renal toxicity
  3. Hepatic toxicity
18
Q

Foscarnet:

  • MOA
  • indications (3)
  • S/E (1)
A

Foscarnet:

- MOA: non-compeitive inhibitor of viral DNA polymerase

- indications:

  1. CMV treatment in pre-engrftment post-BMT
  2. GCV-resistant CMV
  3. CMV retinitis

- S/E: nephrotoxic

19
Q

Describe the following strategies for management of CMV in transplant patients:

  1. Treat
  2. Prophylaxis
  3. Pre-emptive therapy
A

Strategies for management of CMV in transplant patients:

  1. Treat = established disease then start ganciclovir and reduce immunosuppression => but this has HIGH mortlity rates!
  2. Prophylaxis = give GCV/vGCV - generally effective and mains trategy in solid organ transplants (i.e. renal).
  3. 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
20
Q

Antiviral drug now licensed in the UK only for CMV prophylaxis in CMV IgG+ HSCT recipient patients is…

A

Letermovir