Kays Antiviral agents Flashcards
Acyclovir potpurri
- 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
Acyclovir MOA
- inhibits viral DNA polymerase and stops replication
- incorporated into viral DNA and causes chain termination
Acyclovir Resistance
- seen in HSV and VZV
- absence of partial or altered production of viral thymidine kinase
- altered viral DNA polymerase
Acyclovir Spectrum of Activity
- Herpes Simplex Virus 1&2
- Varicella Zoster Virus
- Order of activity: HSV-1>HSV-2>VZV>EBV»CMV
Acyclovir PK
- 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)
Clinical Indications for Acyclovir
- 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
Acyclovir Adverse Effects
- Nephrotoxicity (if given quick bolus, also consider current renal status)
- Neurotoxicity (reversible and seen in patients with renal insufficiency)
Valacyclovir potpurri
- Pro drug of acyclovir
- Same MOA of acyclovir
- same spectrum of activity of acyclovir
- same adverse affects as acyclovir
Valacylclovir PK
- higher bioavailability than acyclovir
- removed after hemodialysis
Acyclovir Clinical indications
- cold sores
- varicella zoster virus infections
- primary, recurrent and prevention of genital herpes
- adjust for renal dysfunction
famicyclovir potpurri
- 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
Famicyclovir SOA
- HSV-1, HSV-2, VZV
Famicyclovir PK
- orally available
- long intracellular half-life, 2 hour plasma.
- can be given with food
- dose reduction in renal dysfunction
Famicyclovir Clinical indications
- cold sores labia
- primary genital HSV, suppression as well
- VZV infections
HIV patients for recurrent orolabial or genital herpes
Famicyclovir Adverse Effects
- Headache and Nausea
- acute renal failure
Ganiciclovir SOA
- Cytomegalovirus (consider primarily this)
- HSV-1, HSV-2, VZV, EBV
Ganiciclovir MOA
- same thymidine kinase MOA as above for HSV and VZV
- In CMV, the triphosphate form inhibits viral DNA polymerase.
Ganiciclovir Resistance
- mutations in ht UL97 gene or mutations in polymerase
Ganicyclovir PK
- low cal bioavailability
- reaches CSF and brain tissue
- plasma half-life 3.5 (long intracellular half-life)
- adjust dose for renal dysfunction
- hemodialysis removes
Ganicyclovir Clinical Indications
- CMV retinitis induction or maintenance
- prevention of CMV in bone marrow in bone marrow and organ transplant recipients
Ganicyclovir adverse effects
- bone marrow suppression
- phlebitis, headache, confusion
- be careful when using with other cytotoxic drugs, probenecid and acyclovir impair GCV excretion
Valganciclovir potpurri
- prodrug of ganicyclovir
- same MOA as gancyclovir
- same SOA as gancyclovir
Valganciclovir PK
- well absorbed good bioavailability
- adjust renal dysfunction
Valganciclovir Indications
- Treatment of CMV retinitis in patients with AIDS. induction and maintenance
- Prevention of CMV in transplant patients at high risk
Valganciclovir Adverse effects
- same as ganciclovir
- hematologic toxicity, severe neutropenia
- inhibition of hematologic toxicity
- potential for birth defects
Letermovir MOA
- inhibits pUL56 subunit of CMV
- inhibits CMV replication and prevention of CMV infections
