MI: Antivirals Pt.1

Question 1

Describe two approaches to antiviral treatment.

Answer 1

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

Question 2

How are viral infections normally detected by the immune system?

Answer 2

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)

Question 3

List some limiting factors for antiviral therapy.

Answer 3

• Impaired host immune response
• Adherence to treatment
• Antiviral drug resistance
• Drug toxicity

Question 4

What is a possible complication of shingles?

Answer 4

Post-herpetic neuralgia

Question 5

How might shingles present differently in immunocompromised patients?

Answer 5

Multi-dermatomal distribution or invasive disease

Question 6

What is the main treatment option for VZV infection?

Answer 6

Aciclovir (PO or IV)

Question 7

Outline the mechanism of action of aciclovir.

Answer 7

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

Question 8

In which 2 ways is aciclovir specific in targeting viruses?

Answer 8

• 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

Question 9

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

Answer 9

Valaciclovir - can only be adminstered orally

Question 10

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

Answer 10

• Foscarnet - viral DNA polymerase inhibitor
• Cidofovir - cytidine analogue

Question 11

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

Answer 11

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

Question 12

What are symptoms of HSV encephalitis

Answer 12

Fever + confusion, seizures, altered consciousness

Question 13

What is HSV meningitis and how should it be treated?

Answer 13

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

Question 14

List some indications for treatment of VZV.

Answer 14

• 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)

Question 15

What is CMV?

Answer 15

Beta-herpesvirus that causes opportunistic infection in immunocompromised patients

Question 16

In which cells does CMV lie dormant?

Answer 16

Monocyte and dendritic cells

Question 17

List some consequences of CMV infection in immunocompromised patients.

Answer 17

• Bone marrow suppression
• Retinitis
• Pneumonitis
• Hepatitis
• Colitis
• Encephalitis

Question 18

What is a characteristic histological feature of CMV infection?

Answer 18

Owl’s eye inclusion

Question 19

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

Answer 19

Ganciclovir (IV) and reduce immunosuppression

Question 20

Which patient group is given ganciclovir as prophylaxis?

Answer 20

Solid-organ transplant patients