Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Year 5 - Pathology > MICRO: Antivirals > Flashcards

MICRO: Antivirals Flashcards

1
Q

What are the main pathways targeted by antivirals?

A
  • Reverse transcription
  • Transcription and translation
  • Release (cell lysis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a virus?

A
  • Obligate intracellular parasites
  • Metabolically inert
  • Rely on host cell for replication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are some virally encoded proteins that can be targeted with DAAs?

A
  • nucleic acid polymerases,
  • proteases,
  • integrase,
  • CCR5,
  • terminase

Viruses encode specific proteins required for cell entry, genomic replication or transcription, assembly and release of progeny virions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are small molecule inhibitors AKA? What is their MOA?

A

Small molecule inhibitors - directly-acting antivirals (DAAs)

Interfere with the function viral proteins and inhibit viral replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does immunomodulation depend on? Give 3 examples of immunomodulation.

A

Boosting the innate immune response e.g. by increasing the production of type 1 interferons (IFNs)

Examples:

  • Interferon for HBV and HCV,
  • IVIG for viral pneumonitis,
  • Imiquimod for HPV,
  • Steroids for HSE (?)
  • IL-6 receptor antagonist for COVID
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

List the herpesviruses and their clinical syndromes. Which ones are rapid vs slow growing?

A

HSV1, HSV2 and VZV are rapid growing

CMV, HHV-6 and HHV-7 are slow growing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Name a complication of chickenpox and zoster in adults.

A

Chickenpox - Pneumonitis

Zoster - Post-herpetic neuralgia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Define prodrug.

A

A prodrug is an inactive precursor of a drug, that is metabolized into the active form within the body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which antivirals are used for HSV and VZV? What do they interfere with?

A

Interfere with viral DNA synthesis

1st line:

  • Aciclovir (po or iv)
  • Valaciclovir (prodrug of aciclovir, po, high bioavailability)
  • Famciclovir

2nd line:

  • Foscarnet or cidofovir for ACV-resistant virus
  • Ganciclovir
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What type of drug is aciclovir? What is its MOA?

A

Guanosine analogue

MOA - Analogue of guanosine but further elongation of the chain by the virus is impossible because acyclovir lacks the 3’ hydroxyl group necessary for the insertion of an additional nucleotide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What herpesviruses are guanosine analogues most selective for?

A

Susceptibility: HSV-1 > HSV-2 >> VZV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why does aciclovir not incorporate into the host DNA?

A

Its affinity for herpesvirus DNA polymerase is 10- to 30- fold higher than for cellular (host) DNA polymerase for ACV-PPP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which enzyme converts aciclovir into the active form?

A
  1. First monophosphorylated by viral thymidine kinase (TK)
  2. Then further phosphorylated by cellular kinases to teh active form (ACV-PPP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q
A

IV aciclovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the treatment for HSV encephalitis?

A

Immediate IV aciclovir 10mg/kg TDS (do not wait for test results)

Treat for 14-21days until PCR negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Give 4 indications for treating VZV.

A
  1. Chickenpox in an adult (risk: pneumonitis)
  2. Zoster in >50yo (risk: post-herpetic neuralgia)
  3. Primary infection or reactivation in immunocompromised
  4. Neonatal chickenpox
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The following statements concern the antiviral drugs oseltamivir and zanamivir. Choose the best answer

  1. Oseltamivir directly inhibits the influenza neuraminidase
  2. Zanamivir blocks binding of viral haemagglutinin to host cell sialic acid
  3. Oseltamivir inhibits influenza virus uncoating
  4. Zanamivir is usually given intravenously
  5. Zanamivir is usually given by nebuliser
A

1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

The following statements concern resistance to antiviral drugs. Choose the best answer.

  1. Resistance of HSV to aciclovir is common in the immunocompetent
  2. Phenotypic resistance testing is routinely used to detect resistance of CMV to ganciclovir
  3. Aciclovir resistance in HSV is most commonly mediated by mutations in the viral thymidine kinase
  4. Aciclovir resistance in HSV is most commonly mediated by mutations in the viral DNA polymerase
  5. Antiviral drug resistance is most commonly associated with good adherence to treatment
A

3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which cells does CMV lie latent in?

A

Monocytes

Dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the symptoms of CMV infection in the immunocompromised?

A

e.g. post transplant:

  • BM suppression,
  • retinitis,
  • pneumonitis,
  • hepatitis,
  • colitis,
  • encephalitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What antivirals are first line for CMV? What can be given alongside these in transplant patients with CMV pneumonitis?

A

1st line

  • Ganciclovir GCV iv
  • OR Valganciclovir (VGC) po – prodrug of ganciclovir

2nd line: Foscarnet IV/intravitreal (for retinitis)

3rd line: Cidofovir IV

Letermovir can also be used.

Transplant patients with CMV pneumonitis = add IVIG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the use of Letermovir in CMV?

A

Can be used as prophylaxis in CMV IgG+ HSCT recipients

GCV/cGCV can also be used prophylactically to prevent CMV especially in solid organ transplant patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which antiviral is only CMV specific (i.e. has no activity against other HHVs)? What is its MOA?

A

Letermovir

MOA: CMV DNA terminase* inhibitor

(* Cleavage and packaging of viral progeny DNA into capsids)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the side effects of Letermovir?

A
  • Mainly safe
  • GI disturbance
  • Drug interactions e.g. with cyclosporine, tacrolimus, sirolimus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the management of SCT patients to prevent CMV?
Pre-emptive therapy used i.e. monitoring eg weekly blood CMV PCR and giving vGCV/GCV or foscarnet Rx when PCR +ve
26
What is the MOA of ganciclovir? What enzyme converts ganciclovir into its active form?
MOA: Guanosine analogue which inhibits viral DNA synthesis Viral UL97 kinase
27
What are the side effects of GCV? How does it compare to ACV?
*Less easily tolerated than ACV* * **BM toxicity** (leukopenia, thrombocytopenia, anaemia, pancytopenia) - contraindicated in those with BM suppression * **Renal and hepatic toxicity (**renally excreted)
28
What antiviral would you give to a BM suppressed patient with CMV?
Foscarnet e.g. pre-engraftment post-BMT Also indicated in: GCV resistance, and CMV retinitis (because intravitreal available)
29
What is the MOA of foscarnet?
_MOA_: Non-competitive inhibitor of viral DNA polymerase; does NOT require activation by phosphorylation
30
What is the main SE of foscarnet?
Nephrotoxic - keep well hydrated and monitor electrolytes
31
What is the MOA of cidofovir? What is its main SE? How is this avoided?
_MOA:_ **Nucleotide (cytidine) analogue**; competitive inhibitor of viral DNA synthesis; does NOT require activation by phosphorylation _SE_: nephrotoxic, requires hydration AND **probenicid** (which prevents its excretion)
32
Which experimental drug has a MOA which inhibits the viral kinase UL97?
Maribavir
33
What is the clinical course of EBV infection?
Salivary transmission Asymptomatic infection (in childhood) OR infectious mononucleosis **Lifelong infection by low grade viral replication in B lymphocytes controlled by immunosurveillance** PTLD/lymphoproliferative disease in the immunosuppresed
34
Define PTLD.
**Post-Transplant Lymphoproliferative Disease** - EBV infection resulting in the breakdown of immunosurveillance, polyclonal expansion of infected B cells and predisposition to lymphoma. Diagnosed by EBV viral load in blood (\> 105 c/ml) or biopsy
35
What is the managament of PTLD?
**Reduce immunosuppression** (regression in \< 50%) **Rituximab** –anti-CD20 mAb
36
Which influenza virus enzyme is involved in releasing new virus into the airway?
Neuraminidase - releases new virus and propagates the infection
37
Name 2 neuraminidase inhibitors. What is first line for influenza treatment?
Effective for both influenza A and B and indicated for all patients in hospital due to influenza related respiratory disease. * 1st line: **Oseltamivir** (Tamiflu PO) * 2nd line: **Zanamivir** (Relenza powder INH or IV) * Also:* * **Peramivir** - Flu A only NB: resistance: H275Y mutation confers reduced susceptibility; not licensed in UK
38
Name the community criteria for neuraminidase inhibitor treatment.
All of the following must apply for community treatment: 1. National surveillance indicates influenza is circulating 2. Patient is in a ‘risk-group’ \* 3. Within 48 hours of symptom onset (36 hours for zanamivir) \*Risks: * Aged ≥ 65 years * Immunosuppressed * Chronic respiratory disease * Chronic heart disease * Chronic liver disease * Chronic neurological disease * Diabetes mellitus * Pregnant women * Morbid obesity (BMI ≥ 40) * Children \< 6 months
39
What is the MAO of Baloxavir (use for influenza)?
_MOA_: Inhibitor of **endonuclease activity of the RNA polymerase** complex required for viral gene transcription _SE_: diarrhoea, bronchitis *Only used in Japan and USA*
40
What dual therapy can be used for synergistic action in influenza?
Favipravir + Oseltamivir _NB: Favipravir MOA_: a viral **RNA polymerase inhibitor** prodrug.
41
True or false? RSV bronchiolitis is associated with subsequent wheeze and asthma diagnosis in later life
True
42
What is the MOA of Ribavirin? What are the adverse effects?
_MOA_: **Guanosine analogue;** Inhibits viral RNA synthesis (exact mechanism unclear). Broad activity in vitro. Oral only _SE:_ anaemia + teratogenicity
43
What is an effective treatment for RSV? When is it indicated?
**_Palivizumab_** - mAb against RSV **_Use_: RSV prevention** in infants at high risk e.g. preterm, underlying cardiac/lung disease, SCID, ventilation Also: **_Nirsevimab_** - has an extended half life and only requires one IM injection for whole winter *NB: ribavirin has unknown clinical efficacy against RSV*
44
Lust 3 types of treatment for SARS-CoV-2.
1. Antiviral drugs 2. Neutralising monoclonal antibodies(nMabs) 3. Immunomodulators
45
Name an antiviral drug used for SARS-CoV2 and its MOA.
**Remdesevir**: Broad spectrum **adenosine nucleotide analogue** pro-drug. iv. _Other_: **Molnupiravir**: Broad spectrum. induces viral RNA mutagenesis **Paxlovid**: Protease inhibitor nirmatrelvir (administered together with low dose ritonavir to increase drug t1/2).
46
Name a nMabs treatment for SARS-CoV2. What is the aim of nMabs use? What is the MOA?
**Ronapreve:** (combination casirivimab + imdevimab), 2.4g iv once only **Sotrovimab**: 500mg iv once only _Aim_: to treat patients who have mild to moderate disease, but **who are at high risk of severe disease.**Administer as early in the disease process. _MOA_: target the S protein to stoDp the virus interacting with ACE2 and entering.
47
Name 2 immunomodulator treatments (incl. to treat CRS) used in SARS-CoV2 and their MOA.
* **Steroids** (eg dexamethasone) _Cytokine Release Syndrome (CRS):_ * **Tocilizumab**: IL-6 receptor antagonist * Sarilumab: IL-6 receptor antagonist * Anakinra: IL-1 receptor antagonist
48
Within how many days of symptom onset can remdesivir be given in SARS-CoV-2? Name a criterion for IL-6 inhibitor use.
**_Remdesivir_** - _\<_10 days - given to all patients **_IL-6 inhibitor -_** CRP \>75mg/L AND sats of \<92% or requiring supplemental oxygen
49
The following statements concern the antiviral drugs oseltamivir and zanamivir. Choose the best answer. * a)Oseltamivir directly inhibits the influenza neuraminidase * b)Zanamivir blocks binding of viral haemagglutinin to host cell sialic acid * c)Oseltamivir inhibits influenza virus uncoating * d)Zanamivir is usually given intravenously * e)Zanamivir is usually given by nebuliser
A - both oseltamivir and zanamivir are NA inhibitors
50
What family does BK virus belong to? What is its clinical course?
Polyomavirus family + related to JC virus ## Footnote Primary infection in childhood with minimal symptoms, but subsequent **lifelong carriage in kidneys and urinary tract**
51
What are the complications of BK virus in the immunocompromised?
BM transplant --\> **haemorrhagic cystitis** Renal transplant --\> **BK nephritis and ureteric stenosis**
52
What is the management of BK haemorrhagic cystitis? What is the first line antiviral?
* Bladder washout * Reduce immunosuppression _1st line:_ **Cidofovir** iv (+ probenicid) _2nd line:_ **Intravesical\* cidofovir** (5mg/kg/wk) in nephrotoxicity
53
What i sthe management of BK nephropathy?
* Reduce immunosuppression if possible * IVIG
54
What is the treatment for adenovirus infection in paeds transplant recipients?
**Adenovirus** --\> severe multi-organ involvement * _1st line:_ **Cidofovir** iv * **IVIG** – sometimes used; limited evidence
55
What is the benefit of using the oral prodrug form of cidofovir?
**Brincidofovir** = lipid-cojugated oral prodrug form of cidofovir **Benefits**: milder toxicity (mainly diarrhoea and mild transaminitis) *BUT not licensed for used in UK. Potential use for adenovirus and BK virus.*
56
What are the uses of cellular immunotherapy?
Cellular immunotherapy = * adoptive * virus-specific cytotoxic T cells * infused from donors Beneficial for: * CMV * Adenovirus * BK virus * EBV in transplants
57
Name and describe two drug resistance mechanisms to antvirals.
_Diversity_ – e.g. presence of quasispecies, mutation / recombination _Selection_ - replication eg in the presence of suboptimal drug concentrations
58
Define quasispecies.
Quasispecies – when viruses are heterogenous rather than monoclonal
59
What is the problem with many second line antiviral treatments when resistance is found?
* Less effective * More toxic * Cross resistance\* may be found e.g. Foscarnet or cidofovir are required for GCV-resistant CMV, but nephrotoxicity can be a problem. **\*Cross-resistance** = when a resistant virus emerging under the selective pressure of one therapy but is also cross-resistant to a second antiviral agent.
60
What are two strategies to prevent drug resistance?
Combination treatment e.g. HAART Improved adherence e.g. OD regimens, patient education
61
When should you test for viral drug resistance? How is this done?
_When:_ * HIV - done at baseline on diagnosis * Other - when treatment fails How: drug resistance assays * **Genotypic** - e.g. for HIV drug resistance * **Phenotypic** - i.e. cell culture or plaque reduction assays e.g. for HSC drug resistance testing
62
What are the two main HSV ACV resistance mechanisms? How is this managed?
Mutations; 1. Viral thymidine kinase (95%) --\> GCV resistance too 2. Viral DNA polymerase (5%) Management: * Foscarnet or cidofovir
63
What are the most common CMV GCV resistance mechanisms? What is the management?
Resistance mechanisms: 1. **Protein kinase gene (UL97) - most common** 2. DNA polymerase gene (UL54) – rare 3. UL56 terminase gene (letermovir) Management: * Foscarnet or cidofovir
64
What is a clinically important mutation conferring reistance to neuraminidase inhibitors?
In H1N1 = H275Y mutation
65
Name a prophylactic IVIG preparation and its use.
Prophylactic: palivizumab (RSV)
66
Name 3 post-exposure prophylaxis IVIG preparations and their uses.
**Varicella zoster immunoglobulin** - for immunocompromised / pregnant / neonates **Hepatitis B immunoglobulin-** unvaccinated recipient exposed to HBV; non-responder to vaccine exposed to source of positive or unknown status **Human Rabies Immunoglobulin (HRIG)**
67
Name 2 therapeutic IVIG preparations and their uses.
**Human normal immunoglobulin (IVIG)** = adjunctive treatment for viral pneumonitis (eg CMV) **Rituximab (anti-CD20) =** for EBV-driven PTLD **Sotrovimab & ronapreve** = neutralising mAbs for COVID Rx
68
The following statements concern resistance to antiviral drugs. Choose the best answer. * a)Resistance of HSV to aciclovir is common in the immunocompetent * b)Phenotypic resistance testing is routinely used to detect resistance of CMV to ganciclovir * c)Aciclovir resistance in HSV is most commonly mediated by mutations in the viral thymidine kinase * d)Aciclovir resistance in HSV is most commonly mediated by mutations in the viral DNA polymerase * e)Antiviral drug resistance is most commonly associated with good adherence to treatment
a) Aciclovir resistance in HSV is most commonly mediated by mutations in the viral thymidine kinase

Year 5 - Pathology (89 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions