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YEAR 5: Microbiology and Infection > MI: Antivirals > Flashcards

MI: Antivirals Flashcards

1
Q

Describe two approaches to antiviral treatment.

A
  • Viral-encoded proteins are a major target (e.g. protease inhibitors) - these are directly-acting antivirals (DAAs)
  • Helping the immune system to clear the virus with the use of immunomodulators (e.g. interferon)
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2
Q

How are viral infections normally detected by the immune system?

A

Viral replication is detected by pattern-recognition receptors which trigger an innate immune response leading to the production of factors (e.g. IFN)

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3
Q

List some limiting factors for antiviral therapy.

A
  • Host immune response
  • Adherene to treatment
  • Antiviral drug resistance
  • Drug toxicity
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4
Q

What is a possible complication of shingles?

A

Post-herpetic neuralgia

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5
Q

How might shingles present differently in immunocompromised patients?

A

Multi-dermatomal distribution or invasive disease

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6
Q

What is the main treatment option for VZV infection?

A

Aciclovir (PO or IV)

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7
Q

Outline the mechnism of action of aciclovir.

A
  • Nucleoside analogue that is incorporated into growing viral DNA and blocks further elongation
  • Requires activation by viral thymidine kinase (which is only present in host cells that are infected by the virus)
  • Aciclovir has a higher affinity for viral DNA polymerase than host DNA polymerase
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8
Q

What is the prodrug of aciclovir?

A

Valaciclovir (PO)

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9
Q

What are two 2nd line treatment options for aciclovir-resistant VZV infection?

A
  • Foscarnet
  • Cidofovir

NOTE: they inhibit viral DNA synthesis

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10
Q

HSV encephalitis is a medical emergency. How should it be treated?

A
  • IMMEDIATE treatment with IV aciclovir 10 mg/kg TDS without waiting for test results
  • If confirmed, treat for 21 days
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11
Q

What is HSV meningitis and how should it be treated?

A
  • Usually self-limiting
  • Immunocompromised patients and those who are unwell enough to require hospital admission require treatment
  • IV aciclovir for 2-3 days followed by oral aciclovir for 10 days
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12
Q

List some indications for treatment of VZV.

A
  • Chickenpox in adults (high risk of pneumonitis)
  • Shingles in adults > 50 years (risk of post-herpetic neuralgia)
  • Infection in immunocompromised patients
  • Neonatal chickenpox
  • If increased risk of complications (e.g. underlying lung disease)
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13
Q

What is CMV?

A

Opportunistic virus that causes severe disease in immunocompromised patients

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14
Q

In which cells does CMV lie dormant?

A

Monocyte and dendritic cells

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15
Q

List some consequences of CMV infection in immunocompromised patients.

A
  • Bone marrow suppression
  • Retinitis
  • Pneumonitis
  • Hepatitis
  • Colitis
  • Encephalitis
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16
Q

What is a characteristic histological feature of CMV infection?

A

Owl’s eye inclusion

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17
Q

What is the 1st line treatment option for CMV infection?

A

Ganciclovir (IV)

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18
Q

How is ganciclovir activated?

A

Requires activation by viral UL97 kinase enzyme

NOTE: ganciclovir is used in conjunction with IVIG in patients with CMV pneumonitis

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19
Q

What is a major side-effect of ganciclovir?

A

Bone marrow toxicity

NOTE: therefore, its use is limited in bone marrow transplant patients

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20
Q

What is the pro-drug of ganciclovir?

A

Valganciclovir (PO)

21
Q

What is the mechanism of action of foscarnet?

A
  • Non-competitive inhibitors of viral DNA polymerase
  • NOTE: foscarnet does NOT require activation
  • Tends to be used in CMV infections if ganciclovir is contraindicated
22
Q

What is a major side-effect of foscarnet?

A

Nephrotoxicity

23
Q

What is the mechanism of action of cidofovir?

A

Competitive inhibitors of viral DNA synthesis (nucleotide analogue)

NOTE: does not require activation

24
Q

What is a major side-effect of cidofovir?

A

Nephrotoxicity (requires hydration and probenecid)

25
Q

What are three strategies for the treatment of CMV in transplant patients?

A
  1. TREAT established disease
  2. PROPHYLAXIS with ganciclovir or valganciclovir (mainly in solid organ transplant patients)
  3. PRE-EMPTIVE THERAPY for bone marrow transplant patients (monitoring for the appearance of CMV in PCR of the blood and starting antiviral therapy when the viral load reaches a threshold)
26
Q

What is the mechanism of action of maribavir?

A

Inhibits viral kinase

Effective in vitro, currently undergoing clinical trials

27
Q

What is the mechanism of action of letermovir?

A

CMV DNA terminase inhibitor

Approved in the USA for CMV prophylaxis in bone marrow transplant patients

28
Q

In which cells does EBV cause continuous low-grade viral replication?

A

B cells

29
Q

What is post-transplant lymphoproliferative disease?

A
  • Polyclonal expansion of B cells associated with immunosuppression used in organ transplant (due to breakdown of immunosurveillance keeping the B cells and EBV in check)
  • This predisposes to lymphoma
30
Q

How is post-transplant lymphoproliferative disease treated?

A
  • Reduce immunosuppression
  • Rituximab (anti-CD20)
31
Q

What are the roles of haemagglutinin and neuraminidase in the influenza virus?

A
  • Haemagglutinin - mediates viral binding and entry into target cell
  • Neuraminidase - allows release of progeny virus particles from the host cell
32
Q

Name two examples of neuraminidase inhibitors.

A
  • Oseltamivir (Tamiflu) - oral
  • Zanamivir (Relenza) - dry powder
33
Q

What are the 3 indications for use of neuraminidase inhibitors in the community according to NICE?

A
  • National surveillance indicates that influenza is circulating
  • Patient is in a risk group
  • Within 48 hours of onset of symptoms
34
Q

What is the most common cause of bronchiolitis?

A

RSV

35
Q

List three treatments for bronchiolitis.

A
  • Ribavirin - nucleoside analogue
  • IVIG - often used as adjunct to treatment of viral pneumonitis in immunocompromised patients
  • Palivizumab - monoclonal antibody against RSV used prophylactically in winter months in high-risk infants (e.g. preterm)
36
Q

What is BK virus?

A

A virus that causes minimal symptoms on primary inection but leads to lifelong carriage in the kidneys and urinary tract (causes problems in immunocompromised patients)

37
Q

What disease states does BK virus cause?

A
  • Bone marrow transplant → haemorrhagic cystitis
  • Renal transplants → BK nephritis and ureteric stenosis
38
Q

Outline the treatment of BK haemorrhagic cystitis.

A
  • Bladder washouts
  • Reduce immunosuppression
  • Cidofovir IV (may consider intravesical)
39
Q

Outline the treatment of BK nephropathy.

A
  • Reduce immunosuppression
  • IVIG

NOTE: cidofovir cannot be used because it is nephrotoxic

40
Q

In which subgroup of patients is adenovirus a major issue?

A

Paediatric transplant patients

41
Q

Outline the treatment of adenovirus infection in transplant patients.

A
  • Cidofovir IV
  • IVIG
  • Brincidofovir (prodrug of cidofovir currently undergoing clinical trials)
42
Q

What is the main cause of antiviral drug resistance?

A

Inadequate drug levels

43
Q

How can antiviral drug resistance be prevented?

A
  • Combination drug therapy
  • Increase adherence (lower pill burden etc.)
  • Sequencing to identify baseline drug resistance
44
Q

Describe two types of drug resistance assays.

A
  • Genotypic assay - identify drug resistance mutations
  • Phenotypic assay - grow the virus in monolayers in the presence of increasing concentrations of antiviral drugs (plaque reduction assay)
45
Q

What are most cases of HSV drug resistance caused by?

A

Mutations in viral thymidine kinase

46
Q

What are most cases of CMV drug resistance caused by?

A

Mutations in protein kinase gene UL97

47
Q

In which patient population is HSV and CMV drug resistance most prevalent?

A

Immunocompromised patients

48
Q

What are the main treatment ooptions for drug resistant HSV and CMV infection?

A

Foscarnet and cidofovir

YEAR 5: Microbiology and Infection (24 decks)

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