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Part 2 Revision > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What viruses does tecovirimat have activity against and what is the target?

A

All orthopoxvirus - it target and inhibits orthopox VP37, inhibiting viral egress

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2
Q

Which antivirals can be used against smallpox?

A

Tecovirimat and brincidofovir (or cidofovir)

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3
Q

What is trifluradine used for?

A

Eye drops for HSV and vaccinia keratitis. It is a nucleoside analogue.

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4
Q

What is brivudine?

A

Nucleoside analogue license ld to treat shingles, but not in UK

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5
Q

Is cidofovir virostatic or virocidal?

A

Virostatic - immune response required to blest infection

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6
Q

Is cidofovir virostatic or virocidal?

A

Virostatic - immune response required to clear infection

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7
Q

What is the main amantadine resistance mutation in influenza A?

A

S31N

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8
Q

What antivirals are available for influenza? Name 8 antivirals

A

M2 ion channels

Amantadine
Rimantidine

Neuraminidase inhibitors

  Oseltamivir 
  Zanamavir
  Peramivir
  Laninamivir

Polymerase inhibitors

 Balixavir
 Favipirivir
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9
Q

What is the mechanism of action of adamantanes?

What virus is this active against?

A

Blocks hydrogen ion influx through M2 ion channel, preventing viral uncoating

Active against flu A but not flu B

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10
Q

What is the mechanism of action of the neuraminidase inhibitors?

A

Analogs of sialic acid, bind the cleavage site of NA so it can’t cleave HA from sialic acid and therefore virus can not be released

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11
Q

Name two influenza polymerase inhibitors and their targets

A

Baloxivir - PA - inhibits cap-dependent endonuclease

Favipirivir - PB1

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12
Q

What are the most common resistance mutations to oseltamivir and zanamavir?

A

Oseltamivir

H1N1 - H275Y
H3N2 - E119V and R292K

Zanamivir

H1N1/H3N2 - Q136K
H3N2 - R292K

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13
Q

What administration routes are 1) oseltamivir, 2) zanamivir, 3) peramivir, 4) baloxivir

A

1) oral
2) inhaled and IV
3) IV infusion
4) oral

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14
Q

What is the administrative route, dose regime and most common resistance mutation for baloxivir?

A

Oral
Single dose
I38T/M/F (more common in H3N2)

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15
Q

Nucleos(t)ide analogues with activity against HSV?

A

Nucleoside
-Acivlovir
-Ganciclovir (less activity but still some)
-Famciclovir (acetylated
penciclovir)

Nucelotide
- Cidofovir
- Adefovir

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16
Q

Non nucleos(t)ide inhibitors with activity against HSV?

A

Foscarnet - pyrophosphate analogue

Pritelivir - Helicase/Primase inhibitor

Amenamevir - (not in use in the UK - approved in Japan)

17
Q

HSV gene mutations conferring resistance to aciclovir and result of mutation?

A

UL23 - TK (95%)
UL30 - DNA pol (5%)

18
Q

Relevant gene mutations in HSV

A

UL 23 - TK - confers ACV resistance
UL30 - DNA pol - Multi class resistance possible - ACV, FOS, CID
UL5/UL52/UL8 - DNA helicase/primase - possible pritelivir resistance

19
Q

Name two helicase-primase inhibitors with activity against HSV

A

Pritelivir

Amenamevir

20
Q

Can tecovirimat be used in pregnancy?

A

Not licensed, should only be used if severe disease, breastfeeding contraindicated.

Vertical transmission is possible (highest risk in first trimester) baby to be tested at birth (throat, urine, blood) if negative vaccinate baby

21
Q

Mechanism of action of pocapavir and limitation of treatment

A

Enterovirus specific capsid inhibitor - blocks viral uncoating and RNA release

Difficult to procure and can only be used for 2 weeks in total

22
Q

Name two IL-6 receptor antagonists for use in COVID infection. When would you initiate these? What should you be cautious of?

A

Toculizumab and Sarilumab

When patients are on oxygen and corticosteroids

Sarilumab is not licensed but can be used if Toculizumab unavailable

Potent immunosuppressors so patients are risk of opportunistic infection. Use in immunosuppressed patients requires caution.

23
Q

Name the JAK-inhibitor used for treating COVID. When would you use this and what are the contraindications?

A

Baricitinib

Age 2+ for patients on oxygen and corticosteroids AND with no evidence of another infection that might be made worse

Can be added to toculizumab or used instead if toculizumab if it can not be tolerated

24
Q

When would you use nirmatrelvir and ritonavir (paxlovid)?

A

In patients presenting within 5 days
Not requiring oxygen but are high risk of severe disease

25
Q

What window do you need with treat flu within for the following:

  1. Oseltamivir
  2. Zanamavir in adults
  3. Zanamavir in children
  4. IV Zanamavir
A
  1. Within 48 h (up to 5 days off-label)
  2. Within 48 h
  3. Within 36 h
  4. Within 6 days
26
Q

In which situations would you consider using IV zanamivir to treat influenza?

A

Severely immunosuppressed patients with complicated flu (in H1 season) who are unable to use diskhaler

Severely immunosuppressed patients with severe complications such as multi organ failure (in H1 season)

27
Q

In what age is zanamivir licensed? Dose and duration of treatment?

A

Over 5 years

10 mg BD 5 days

28
Q

Do zanamivir and oseltamivir require dose adjustment for

1) renal dysfunction
2) hepatic dysfunction

A

1) Oseltamivir = yes, inhaled zanamavir = no, IV zanamavir = yes

2) Oseltamivir = no, inhaled zanamavir = no, IV zanamavir = yes

29
Q

What class of drug is nirmatrelvir? What drug is added to this to treat COVID? And who would you treat with this regimen?

A

Protease inhibitor

Ritonavir

COVID patients without oxygen requirements, who are at high risk of severe disease

30
Q

What class of drug is remdesivir? When would you use it for COVID treatment? What is administration route?

A

RNA polymerase inhibitors (adenosine nucleotide prodrug)

Patients at high risk of severe disease

IV

31
Q

What is the mechanism of action of molnupiravir? When would you use it in COVID treatment? What is administration route?

A

Nucleoside analogue which causes mutagenesis in the viral RNA

Adults at high risk of disease, within 5 days of symptoms, who do not require O2 (can be used interchangeably with paxlovid)

Oral

32
Q

What class of drug is toculizumab? What other drug is the same class can be used instead? What specifically are patients at risk of?

A

IL6 receptor antagonist

Sarilumab

Potent immunosuppressant so patients are at risk of opportunistic infection

33
Q

What class of drug is Baricitinib? When specifically should this not be used?

A

Janus Kinase (JAK) inhibitors

Cannot be used if patients have evidence of any other infection that could be made worse with treatment

34
Q

What is Tabelecleucel?

A

Off the shelf EBV specific cytotoxic T cells for use in relapsing and refractory EBV+ PTLD

35
Q

What type of drug is ribavirin?

A

Nucleoside (guanosine) analogue

36
Q

What is rituximab? How long does the induced B cell suppression last for? What are the implications of this?

A

Anti- CD20 MAb

2-6 months

At risk of opportunistic infections and unable to have vaccination during this time due to likely poorer responses

37
Q

What is CAR-T therapy and what implications does it have in virology?

A

Chimeric antigen receptor T cell therapy

Patients T cells are modified to include a receptor to recognise and kill cancer cells

Can be used in refractory B cell ALL, DLBCL, B cell and mantel cell lymphoma

Patients are severely immunosuppressed and can be at risk of viral reactivation and opportunistic infection

Part 2 Revision (37 decks)

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