Antibiotics: Antivirals

Question 1

Strategies to prevent/treat viral infections:

Answer 1

1. Withdrawal of immunosuppression (if present)
2. Protection from exposure
3. Prophylaxis for the at-risk individual
4. Immune globulin (IVIG)
5. Antiviral drugs

Question 2

Nucleoside/nucleotide analogues:

Answer 2

Targets: DNA replication
Used against: Herpes, HBV, HIV
Important drugs: Acyclovir (herpes), ganciclovir (CMV), ribavirin (HCV)

Question 3

M2 ion channel inhibitors:

Answer 3

Targets: Capsid uncoating

Used against: Influenza A

Question 4

Neuraminidase inhibitors:

Answer 4

Targets: Release of virions
Used against: Influenza
Important drugs: zanamivir, oseltamivir
These drugs are useful as prophylaxis, and may reduce duration of symptoms by 1-3 days when starting within 24 hours of illness onset. It reduces the risk of complications, including hospitalization and respiratory failure.

Question 5

Interferon alpha:

Answer 5

Targets: Immune response

Used against: HBV, HCV

Question 6

Protease inhibitors:

Answer 6

Targets: Viral capsid assembly

Used against: HCV

Question 7

Host-cell targets:

Answer 7

Targets: Receptors and proteases

Used against: Influenza

Question 8

Clinical use of acyclovir:

Answer 8

HSV: orolabial infections, herpes genitalis, HSV encephalitis (IV only), neonatal HSV.
VZV: varicella, herpes zoster

Question 9

Hepatitis B infection:

Answer 9

> 90% of acute infections resolve. Risk of chronic infection is increased in perinatal infection and immunocompromised patients. Persons with persistent HBV infection have 20-40% lifetime risk of cirrhosis or HCC.

Question 10

Treatment for chronic HBV infection:

Answer 10

Interferons (interferon alpha, pegylated interferon), nucleoside analogues (lamivudine, entecavir, telbivudine), nucleotide analogues (adefovir, tenofovir).
Interferons are IV only, toxicity may be limiting, but there is no resistance.
Nucleoside/nucleotide analogues are oral, generally well-tolerated, and resistance and cross-resistance occurs in most patients over time.

Question 11

Results of HBV treatment:

Answer 11

Reduction of serum HBV titer
Undetectable serum DNA in many patients
Normalization of ALT
Improvement in liver histology
HBeAg seroconversion
HBsAg seroconversion is less common

Question 12

Hepatitis C treatment:

Answer 12

Alpha interferon
Ribavirin (a guanosine analogue that interferes with the binding of viral RNA to ribosomes)
Protease inhibitors (telaprevir, toceprevir)
Treatment results in: a drop in HCV RNA load, normalization of LFTs, improvement in liver histology, and sustained (>6 month) improvement in 50-60%.