Antiviral Medications

Question 1

Acyclovir MOA (3):

Answer 1

• Acyclovir is phosphorylated to the inactive monophosphate form by a virus specific thymidine kinase and to the activated triphosphate form by cellular enzymes.
• Inhibits viral DNA polymerases and competes with deoxyguanosine triphosphate.
• Acts as a chain terminator.

Question 2

Acyclovir pharmacokinetics (4):

Answer 2

• Renal adjustment required.
• Bioavailability 10 - 30%.
• Good CSF penetration (drug of choice for viral meningitis).
• Placenta and umbilical cord penetration.

Question 3

Acyclovir ADRs (4):

Answer 3

• IV can cause phlebitis.
• Reversible renal toxicity due to crystalline nephropathy.
• GI: N/V/D.
• Hepatic.

Question 4

Acyclovir clinical uses (5):

Answer 4

• Therapy started 48-72 hours of symptoms.
• Primary HSV-2: 10 days.
• Recurrent HSV-2: 5 days.
• IV for encephalitis (drug of choice).
• NOT for CMV.

Question 5

Valacyclovir:

Answer 5

Prodrug of acyclovir.

Question 6

Valacyclovir pharmacokinetics (2):

Answer 6

• 70% bioavailability.

- Converted to acyclovir by first pass metabolism and hydrolysis.

Question 7

Valacyclovir ADRs (3):

Answer 7

High doses:

• Confusion, hallucinations.
• Nephrotoxicity.
• Thrombocytopenic syndromes.

Question 8

Valacyclovir clinical uses (3):

Answer 8

• Herpes Zoster.
• Herpes Simplex.
• Recurrent HSV in HIV infected patients.

Question 9

Valacyclovir advantage over acyclovir:

Answer 9

Less frequent dosing (BID vs TID-5x day).

Question 10

Ganciclovir:

Answer 10

Acyclic nucleoside analogues of guanine similar to acyclovir.

Question 11

Ganciclovir MOA:

Answer 11

Metabolized by thymidine kinase and other enzymes into triphosphate analog which inhibits DNA polymerase and incorporates into viral DNA.

Question 12

Ganciclovir pharmacokinetics (4):

Answer 12

• Inhibition of CMV and EBV.
• HSV.
• VZV.
• Oral bioavailability 6-9%.

Question 13

Ganciclovir ADRs (3):

Answer 13

• Bone marrow suppression.
  
  • Neutropenia, thrombocytopenia and anemia.
• CNS.
• GI (N/V).

Question 14

Ganciclovir clinical uses (4):

Answer 14

• CMV retinitis.
• CMV prophylaxis in transplant pts.
• IV: esophagitis, gastritis and colitis.
• Surgically implanted device for CMV retinitis in AIDS.

Question 15

Valganciclovir:

Answer 15

Prodrug of ganciclovir.

Question 16

Valganciclovir pharmacokinetics (2):

Answer 16

• Bioavailability ~ 60%.

- Renally excreted (adjustment required).

Question 17

Valganciclovir clinical uses (2):

Answer 17

• CMV retinitis.

- CMV prophylaxis.

Question 18

Penciclovir (3):

Answer 18

• Acyclic guanine nucleoside analog.
• Topical cream only.
• HSV-1 (cold sores).

Question 19

Famciclovir (7):

Answer 19

• Prodrug of penciclovir.
• Bioavailability 65-77%.
• Renally excreted (adjustment required).
  ADRs:
• CNS.
• GI.
  Uses:
• Herpes zoster.
• HSV.

Question 20

Cidofovir ADRs (4):

Answer 20

• Nephrotoxic (avoid SCr > 1.5 mg/dl).
• Neutropenia.
• Ocular hypotony.
• Metabolic acidosis.

Question 21

Cidofovir clinical uses

Answer 21

• Administer with probenecid and normal saline (nephrotoxicity).
• Reserved for CMV retinitis in AIDS pts.

Question 22

Foscarnet MOA:

Answer 22

Competes for pyrophosphate site in viral but not human DNA polymerase and reverse transcriptase.

Question 23

Foscarnet ADRs (6):

Answer 23

• Nephrotoxic.
• Electrolyte disturbances.
• CNS (seizures, fever).
• Anemia/neutropenia.
• GI (N/V/D).
• EKG changes.

Question 24

Foscarnet clinical uses (3):

Answer 24

• Second line agent.
• CMV retinitis in pts with AIDS.
• Acyclovir resistant mucocutaneous HSV in immunosuppressed.

Question 25

Lamivudine MOA:

Answer 25

Metabolized to ddATP which inhibits reverse transcriptase and incorporates into viral DNA.

Question 26

Lamivudine pharmacokinetics (2):

Answer 26

• Bioavailability 80-90%.

- Renally eliminated (adjustment required).

Question 27

Lamivudine ADRs (6):

Answer 27

• GI (diarrhea).
• CNS.
• Musculoskeletal (arthralgias).
• Rash
  BLACK BOX:
• Lactic acidosis.
• Severe hepatomegaly (fatty liver-steatosis).

Question 28

Lamivudine clinical uses (2):

Answer 28

• Hepatitis B virus (with interferon).

- HIV.

Question 29

Ribavirin pharmacokinetics (4):

Answer 29

• Bioavailability 50%.
• Food increases absorption.
• Half life 200-300 hours at steady state.
• Renally eliminated (caution CrCl < 50 ml/min).

Question 30

Ribavirin ADRs (5):

Answer 30

- Anemia.
With interferon:
- Fatigue.
- Rash.
- Pruritus.
- Depression.

Question 31

Ribavirin clinical uses (2):

Answer 31

• RSV bronchiolitis and pneumonia in children.

- Hepatitis C (with interferon alpha).

Question 32

Imiquimod (3):

Answer 32

• Topical tx of condylomata acuminate.
• Induces local INF-alpha, beta, gamma and TNF gamma.
• Reduced viral load/wart size.

Question 33

Amantadine/rimantidine (5):

Answer 33

• Prevents virus from entering susceptible cells.
• Prophylaxis of influenza A.
  Amantadine:
• CNS adverse effects are worse.
• Requires renal adjustment.
• Tx parkinsonism.

Question 34

Osteltamivir/zanamivir:

Answer 34

• Inhibitor of influenza virus neuroaminidase (release of virus from cell).
• Influenza A and B.