W29 - Antivirals

Question 1

Herpesviruses 3 subfamilies?

Answer 1

1. Alpha
2. Beta
3. Gamma

Question 2

Members of herpesviruses subfamilies:

• Alpha?
• Beta?
• Gamma?

Answer 2

Members of herpesviruses subfamilies:

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

Question 3

Which herpesvirus subfamily has latency in sensory ganglia?

Answer 3

Alpha (HSV-1, HSV2, VZV)

Question 4

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

Answer 4

Varicella pneumonia (chickenpox pneumonitis)

• more common in those with lymphom or severely immunocompromised

Question 5

Describe zoster in

A) immunocompetent

B) immunocompromised

Answer 5

Describe zoster in

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

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

Question 6

4 typical advatnages of a prodrug

Answer 6

Generally:

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

Question 7

First line antiviral drugs for HSV and VZV?

Answer 7

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

Question 8

acyclovir drug class & MOA

Answer 8

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

Question 9

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

Answer 9

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

Question 10

HSV encephalitis:

• treatment?

Answer 10

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 -

Question 11

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

Answer 11

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

Question 12

CMV latency in which cells?

Answer 12

Some monocyte and dentritic cell precursors

Question 13

When does CMV become problematic?

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

Mostly active against CMV.

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

Question 16

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

Answer 16

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

Question 17

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

Answer 17

Less tolerated than ACV

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

Question 18

Foscarnet:

• MOA
• indications (3)
• S/E (1)

Answer 18

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

Question 19

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

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

Answer 19

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

Question 20

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

Answer 20

Letermovir