Antivirals

Question 1

Valacyclovir
Brand name
Type
Use
Mechanism
Adverse rxns

Answer 1

• Valtrex
• Prodrug. Guanosine analogue.
• Use – HSV1 / 2 (mainly), VZV, and EBV. May be used for prophylaxis as well.
• Mechanism – Specific to infected cells due to viral thymidine kinase (TK) converting drug to acyclovir triphosphate (active form; guanosine analogue), which inhibits viral DNA synthesis via competitive inhibition of viral DNA polymerase → chain termination.
• Adverse rxns – elevated LFTs and nephrotixicity due to drug crystallization.

Question 2

Ganciclovir
Type
Use
Mechanism
Adverse rxns

Answer 2

• Guanosine analogue
• Use – CMV / CMV retinitis.
• Mechanism – CMV kinase in CMV-infected cells converts ganciclovir to monophosphate → → triphosphate which inhibits viral DNA polymerase → chain termination.
• Adverse rxns – anemia, neutropenia, thrombocytopenia

Question 3

Cidofovir
Type
Use
Mechanism
Adverse rxns
Precautions

Answer 3

• Cytosine analogue
• Use – CMV (mainly; retinitis), HSV, adenovirus, papillomavirus
• Mechanism – Inhibits viral DNA polymerase but does not require activation
• Adverse rxns – nephrotoxicity, neutropenia, anemia, uveitis / iritis
• Precautions – must prehydrate w/ 1L normal saline

Question 4

Telbivudine
Type
Use
Mechanism

Answer 4

• Thymidine analogue
• Use – Hep B
• Mechanism – Drug phosphorylated → triphosphate. Competitively inhibits HBV DNA polymerase

Question 5

Interferons
Natural function
Use
Mechanism
Adverse rxns

Answer 5

• IFN is an immunostimulant normally made by leukocytes and fibroblasts
• Use – Hep B / C (mainly), HIV, suppress tumor growth
• Mechanism – activate killing ability of NK cells and macrophages. Antiproliferative effect on tumor cells. PEG (polyethylene glycol) increases duration of action.
• Adverse rxns – flu-like rxns, IFN-a causes CNS probs (depression, confusion, anxiety, psychosis)

Question 6

Ribavirin
Type
Use
Mechanism
Adverse rxns
Precaution

Answer 6

• Purine analogue
• Use – Many DNA / RNA dependent viruses: Hep C (mainly), HSV, VSV, RSV (respiratory syncytial virus), influenza, parainfluenza, paramyxovirus, HIV1
• Mechanism – Phosphorylated → triphosphate. Inhibits GTP synthesis by inhibiting inositol monophosphate dehydrogenase (IMPDH). Inhibits viral RNA polymerase. Increases mutation rate of viral RNA so virions aren’t produced. Give for 24-48 weeks.
• Adverse rxns – anemia / neutropenia, rash / itching
• Precaution – pregnancy risk X. Use 2 forms of contraception and women should not conceive for 6 months afterwards.

Question 7

Boceprevir
Use
Mechanism
Adverse rxns

Answer 7

• Use – Hep C (never used alone; use in combo w/ ribavirin)
• Mechanism – NS3/4 Hep C serine protease inhibitor → inability to cleave HCV polyprotein
• Adverse rxns – dysgeusia (altered sense of taste). Anemia.

Question 8

What does hemagglutinin do?

Answer 8

Hemagglutinin on influenza virus binds to sialic acid-containing surface receptor → endocytosis. Protons enter capsid via M2 ion channel in endosome → aid in uncoating of virus.

Question 9

What does neuranimidase do?

Answer 9

Neuranimidase is required for release. Cleaves the complex that hemagglutinin binds to, allowing the virus to float away.

Question 10

Amantadine
Use
Mechanism
Adverse rxns

Answer 10

• Use – tx or prophylaxis for influenza A, especially immunosuppressed pxs, nursing home pxs, and healthcare workers. Must be used w/in 1-2 days of sx onset. Also potentiates DA for Parkinson’s tx.
• Mechanism – Blocks M2 proton channels in viral membrane, preventing uncoating and release of RNA.
• Adverse rxns – Anticholinergic effects may cause mydriasis, urinary retention, etc.

Question 11

Oseltamivir
Brand Name
Use
Mechanism

Answer 11

• Tamiflu
• Use – Tx and prophylaxis for influenza A / B
• Mechanism – Prodrug. Mimics / competes with sialic acid, blocking ability of neuraminidase to cleave sialic acid-containing receptors to which hemagglutinin binds → inability to release virions.