Kays Antiviral agents

Question 1

Acyclovir potpurri

Answer 1

• needs to be converted to active form acyclovir triphosphate
• Viral thymidine kinase is in Herpes Simplex Virus and Varicella Zoster Virus
• these viruses initially phosphorylate the drug and then host cells do the next 2 phosphorylations

Question 2

Acyclovir MOA

Answer 2

• inhibits viral DNA polymerase and stops replication

- incorporated into viral DNA and causes chain termination

Question 3

Acyclovir Resistance

Answer 3

• seen in HSV and VZV
• absence of partial or altered production of viral thymidine kinase
• altered viral DNA polymerase

Question 4

Acyclovir Spectrum of Activity

Answer 4

• Herpes Simplex Virus 1&2
• Varicella Zoster Virus
• Order of activity: HSV-1>HSV-2>VZV>EBV»CMV

Question 5

Acyclovir PK

Answer 5

• oral bioavailability 10-20% (dose-dependent oral absorption)
• widely distributed in all tissues and body
• renally eliminated (adjust for renal dysfunction) half-life 2.5-3.5 hours)

Question 6

Clinical Indications for Acyclovir

Answer 6

• Herpes Simplex Virus Infections, and suppression (primary/recurrent genital HSV)
• Herpes Simplex Virus encephalitis
• VZV shingles in immunocompromised hosts, adult with chicken pox
• prevention of HSV and CMV in transplant patients

Question 7

Acyclovir Adverse Effects

Answer 7

• Nephrotoxicity (if given quick bolus, also consider current renal status)
• Neurotoxicity (reversible and seen in patients with renal insufficiency)

Question 8

Valacyclovir potpurri

Answer 8

• Pro drug of acyclovir
• Same MOA of acyclovir
• same spectrum of activity of acyclovir
• same adverse affects as acyclovir

Question 9

Valacylclovir PK

Answer 9

• higher bioavailability than acyclovir

- removed after hemodialysis

Question 10

Acyclovir Clinical indications

Answer 10

• cold sores
• varicella zoster virus infections
• primary, recurrent and prevention of genital herpes
• adjust for renal dysfunction

Question 11

famicyclovir potpurri

Answer 11

• prodrug of peniciclovir that is a nucleoside analogue that is similar to acyclovir
• gets phosphorylated by viral thymidine kinase and further phosphorylated by hosts cells subsequently
• less potent than acyclovir by 100 fold

Question 12

Famicyclovir SOA

Answer 12

• HSV-1, HSV-2, VZV

Question 13

Famicyclovir PK

Answer 13

• orally available
• long intracellular half-life, 2 hour plasma.
• can be given with food
• dose reduction in renal dysfunction

Question 14

Famicyclovir Clinical indications

Answer 14

• cold sores labia
• primary genital HSV, suppression as well
• VZV infections
  HIV patients for recurrent orolabial or genital herpes

Question 15

Famicyclovir Adverse Effects

Answer 15

• Headache and Nausea

- acute renal failure

Question 16

Ganiciclovir SOA

Answer 16

• Cytomegalovirus (consider primarily this)

- HSV-1, HSV-2, VZV, EBV

Question 17

Ganiciclovir MOA

Answer 17

• same thymidine kinase MOA as above for HSV and VZV

- In CMV, the triphosphate form inhibits viral DNA polymerase.

Question 18

Ganiciclovir Resistance

Answer 18

• mutations in ht UL97 gene or mutations in polymerase

Question 19

Ganicyclovir PK

Answer 19

• low cal bioavailability
• reaches CSF and brain tissue
• plasma half-life 3.5 (long intracellular half-life)
• adjust dose for renal dysfunction
• hemodialysis removes

Question 20

Ganicyclovir Clinical Indications

Answer 20

• CMV retinitis induction or maintenance

- prevention of CMV in bone marrow in bone marrow and organ transplant recipients

Question 21

Ganicyclovir adverse effects

Answer 21

• bone marrow suppression
• phlebitis, headache, confusion
• be careful when using with other cytotoxic drugs, probenecid and acyclovir impair GCV excretion

Question 22

Valganciclovir potpurri

Answer 22

• prodrug of ganicyclovir
• same MOA as gancyclovir
• same SOA as gancyclovir

Question 23

Valganciclovir PK

Answer 23

• well absorbed good bioavailability

- adjust renal dysfunction

Question 24

Valganciclovir Indications

Answer 24

• Treatment of CMV retinitis in patients with AIDS. induction and maintenance
• Prevention of CMV in transplant patients at high risk

Question 25

Valganciclovir Adverse effects

Answer 25

• same as ganciclovir
• hematologic toxicity, severe neutropenia
• inhibition of hematologic toxicity
• potential for birth defects

Question 26

Letermovir MOA

Answer 26

• inhibits pUL56 subunit of CMV

- inhibits CMV replication and prevention of CMV infections