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Arjun's PM copy-Microbiology and Infection > MI: Antivirals > Flashcards

MI: Antivirals Flashcards

1
Q

Describe two approaches to antiviral treatment.

A
  • Drugs targetting viral proteins
  • Drugs that modulate host immune response (e.g. interferon)
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2
Q

How are viral infections normally detected by the immune system?

A

Viral genetic material and proteins are detected by pattern-recognition receptors which trigger an innate immune response leading production of anti-viral cytokines (e.g. interferon)

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3
Q

List some limiting factors for antiviral therapy.

A
  • Impaired host immune response
  • Adherence 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 mechanism of action of aciclovir.

A

It is a nucleoside (guanosine) analogue inhibits viral DNA polymerase and also blocks strand elongation (lacks 3’ OH group)

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8
Q

In which 2 ways is aciclovir specific in targeting viruses?

A
  • Requires activation by viral thymidine kinase (which is only present in host cells that are infected by the virus)
  • Has a higher affinity for viral DNA polymerase than host DNA polymerase
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9
Q

What is the prodrug of aciclovir? How does it differ from aciclovir?

A

Valaciclovir - can only be adminstered orally

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10
Q

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

A
  • Foscarnet - viral DNA polymerase inhibitor
  • Cidofovir - cytidine analogue
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11
Q

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

A
  • IMMEDIATE treatment with IV aciclovir 10 mg/kg TDS on clinical suspicion without waiting for test results
  • If confirmed, treat for 14-21 days
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12
Q

What are symptoms of HSV encephalitis

A

Fever + confusion, seizures, altered consciousness

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13
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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14
Q

List some indications for treatment of VZV.

A
  • Infection in adults (high risk of pneumonitis)
  • Shingles in > 50 years (risk of post-herpetic neuralgia)
  • Infection in immunocompromised patients
  • Neonatal infection
  • If increased risk of complications (e.g. underlying lung disease)
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15
Q

What is CMV?

A

Beta-herpesvirus that causes opportunistic infection in immunocompromised patients

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16
Q

In which cells does CMV lie dormant?

A

Monocyte and dendritic cells

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17
Q

List some consequences of CMV infection in immunocompromised patients.

A
  • Bone marrow suppression
  • Retinitis
  • Pneumonitis
  • Hepatitis
  • Colitis
  • Encephalitis
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18
Q

What is a characteristic histological feature of CMV infection?

A

Owl’s eye inclusion

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19
Q

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

A

Ganciclovir (IV) and reduce immunosuppression

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20
Q

Which patient group is given ganciclovir as prophylaxis?

A

Solid-organ transplant patients

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21
Q

Describe pre-emptive therapy for CMV

A

Used for HSCT transplant patients

  • Monitoring with weekly blood CMV PCR
  • Gancicolvir/valganciclovir initiated when viral load reaches certain threshold e.g. 1000 c/ml
  • This threshold is a reached a week before the onset of disease
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22
Q

What is the mechanims of action of ganciclovir? How is it activated?

A
  • Nucleoside analogue that inhibits viral DNA polymerase and also halts chain elongation
  • Activated by viral UL97 kinase
23
Q

What is the pro-drug of ganciclovir?

A

Valganciclovir (given PO)

24
Q

What are 2nd line treatments for CMV?

A
  1. Foscarnet (IV/intravitreal)
  2. Cidofovir
  3. Maribavir
25
Q

What is the mechanism of action of foscarnet?

A
  • Non-competitive inhibitor of viral DNA polymerase

NOTE: does not require activation

26
Q

What is a major side-effect of foscarnet?

A

Nephrotoxicity

27
Q

What is the mechanism of action of cidofovir?

A

Cytidine analogue that competitively inhibits viral DNA synthesis

NOTE: does not require activation

28
Q

What is a major side-effect of cidofovir?

A

Nephrotoxicity (requires hydration and probenecid)

29
Q

How is CMV pneumonitis treated?

A

Ganciclovir with IVIG

30
Q

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

A
  1. TREAT established disease
  2. PROPHYLAXIS (mainly in solid organ transplant patients)
  3. PRE-EMPTIVE THERAPY (for bone marrow transplant patients)
31
Q

What is the mechanism of action of maribavir?

A

Inhibits viral kinase UL97

Effective in vitro, currently undergoing clinical trials

32
Q

What is the mechanism of action of letermovir? What is it used for?

A
  • CMV DNA terminase inhibitor
  • Used for CMV prophylaxis in IgG-positive HSCT patients
33
Q

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

A

B cells

34
Q

What is post-transplant lymphoproliferative disease (PTLD)?

A
  • Polyclonal expansion of B cells associated with immunosuppression used in organ transplant
  • This is due to breakdown of immunosurveillance keeping the B cells and EBV in check
  • This predisposes to lymphoma
35
Q

How is post-transplant lymphoproliferative disease diagnosed and treated?

A

Diagnosis: EBV viral load >10^5 c/ml in blood + positive biopsy

Treatment

  • Reduce immunosuppression
  • Rituximab (anti-CD20)
36
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 to infect neighbouring cells
37
Q

Name two examples of neuraminidase inhibitors.

A
  • Oseltamivir (Tamiflu) - oral
  • Zanamivir (Relenza) - dry powder
38
Q

What is the most common cause of bronchiolitis?

A

RSV

39
Q

List three treatments for bronchiolitis and their mechanism of action

A
  • Ribavirin - guanosine analogue
  • IVIG - often used as adjunct to treatment of viral pneumonitis in immunocompromised patients
  • Palivizumab - monoclonal antibody against RSV F (fusion) protein. Used for prophylaxis against serious infection in high-risk infants (e.g. BPD)

No real drug against active RSV.

40
Q

What drug is used to treat monkeypox? When is it used?

A

Tecoviromat

  • Severe disease - >100 lesions, encephalitis, sepsis
  • Anatomical concern - eye lesions, dysphagia, urinary retention
  • High-risk patient - immunocompromised, pregnant, paediatric
41
Q

What is BK virus? What diseases can it cause and in which groups of patients?

A

A ubiquitous virus that is asymptomatic

  • Can cause haemorrhagic cystitis in HSCT patients
  • Can cause BK nephritis and ureteric stenosis in renal transplant patients
42
Q

Outline the treatment of BK haemorrhagic cystitis.

A
  • Bladder washouts
  • Reduce immunosuppression
  • Cidofovir IV (may consider intravesical)
43
Q

Outline the treatment of BK nephropathy.

A
  • Reduce immunosuppression
  • IVIG

NOTE: cidofovir cannot be used because it is nephrotoxic

44
Q

In which subgroup of patients is adenovirus a major issue?

A

Paediatric transplant patients - can cause disseminated disease

Adenovirus is very common and usually causes self-limiting respiratory, GI, and conjunctival infection

45
Q

Outline the treatment of adenovirus infection in transplant patients.

A
  • Cidofovir IV
  • IVIG
46
Q

Describe how cellular immunotherapy may be used to treat viral infection

A

Patient CD8 T cells are isolated then exposed to specific viral antigens, and then reinfused

Now increasingly used as second line therapy for a range of viral infections in transplant recipients.

47
Q

What is the main cause of antiviral drug resistance?

A

Inadequate drug levels

48
Q

How can antiviral drug resistance be prevented?

A
  • Combination drug therapy
  • Increasing adherence (e.g. therapies with lower pill burden)
  • Sequencing to identify baseline drug resistance
49
Q

Describe two types of drug resistance assays.

A
  • Genotypic assay - identify drug resistance mutations - used in HIV
  • Phenotypic assay - grow the virus in monolayers in the presence of increasing concentrations of antiviral drugs (plaque reduction assay) - routinely used for HSV
50
Q

What are most cases of HSV drug resistance caused by?

A

Mutations in viral thymidine kinase

51
Q

What are most cases of CMV drug resistance caused by?

A

Mutations in UL97 protein kinase gene

52
Q

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

A

Foscarnet and cidofovir

53
Q

How does oseltamivir resistance occur?

A

Neuraminidase mutation

54
Q

Name some pre- and post-exposure uses of antibodies?

A

Pre-exposure

  • Palivizumab - RSV bronchiolitis

Post-exposure

  • HBV Ig - neonate
  • Rabies Ig - risky bite in unvaccinated
  • VZIG - pregancy

Arjun's PM copy-Microbiology and Infection (26 decks)

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