2 - Systemic Antiviral Agents Flashcards
Once viruses such as human herpes viruses and HIV are acquired, antiviral agents are essentially the sole method of treatment
True
The human herpes viruses family includes human herpes virus type 1/HSV-1 and human herpes virus type 2/HSV-2 which most commonly causes herpes labialis and genital herpes respectively, although both types of lesions can be caused by either virus
True
HSV-1 and HSV-2 have been shown to cause gingivostomatitis
True
HSV-1 and HSV-2 have been shown to cause ocular disease
True
HSV-1 and HSV-2 have been shown to cause herpes gladiatorum
True
HSV-1 and HSV-2 have been shown to cause eczema herpeticum
True
HSV-1 and HSV-2 have been shown to cause herpetic whitlow (paronychia)
True
HSV-1 and HSV-2 have been shown to cause neonatal herpes
True
HSV-1 and HSV-2 have been shown to cause lumbosacral herpes
True
HSV-1 and HSV-2 have been shown to cause herpetic keratoconjunctivitis
True
HSV-1 and HSV-2 have been shown to cause herpes encephalitis
True
HSV-1 and HSV-2 have been shown to cause cervicitis
True
HSV-1 and HSV-2 have been shown to cause erythema multiforme
True
Human herpes virus type 3 is also known as varicella-zoster virus (VZV), more commonly called chicken pox in its primary form and shingles/herpes zoster in its recurrent form
True
Human herpes type 4 is EBV which causes infectious mononucleosis and Burkitt’s lymphoma
True
Human herpes virus type 5 is CMV which causes CMV retinitis
True
Human herpes virus type 6 causes roseola infantum
True
Human herpes virus type 7 causes pityriasis rosea
True
Human herpes virus type 8 is Kaposi’s sarcoma herpes virus and causes Kaposi’s sarcoma
True
The 3 primary antiviral drugs with efficacy against HSV-1, HSV-2 and VZV are acyclovir, valacyclovir and famciclovir
True
Acyclovir is a guanosine analog
True (valacyclovir is the oral prodrug of acyclovir)
Valacyclovir is the oral prodrug of acyclovir
True
Activation of acyclovir requires phosphorylation by herpes-specific thymidine kinase prior to bi- and triphosphorylation by host cellular GMP kinase enzymes
True (the active triphosphorylated acyclovir inhibits viral DNA polymerase causing irreversible inhibition of further viral DNA synthesis)
Step 1 = viral thymidine kinase (phosphorylates acyclovir/penciclovir)
Step 2 = human cellular-GMP kinase and other cellular kinases (further phosphorylates acyclovir/penciclovir monophosphate)
Step 3 = acyclovir/penciclovir triphosphate competes with normal deoxyguanosine triphosphate for viral-DNA polymerase
Step 4 = incorporation of acyclovir/penciclovir triphosphate into viral DNA (leads to chain termination and reduced viral replication)
Acyclovir does not undergo any hepatic microsomal metabolism
True
Acyclovir and Valacyclovir has roughly equal urine and faecal excretion
True(Valacyclovir is the oral prodrug of Acyclovir)
Valacyclovir does not undergo any hepatic microsomal metabolism, but is converted to acyclovir
True (acyclovir also does not undergo any hepatic microsomal metabolism)
Famciclovir is the oral prodrug of penciclovir
True (just as Valacyclovir is the oral prodrug of acyclovir)
Viral thymidine kinase converts the active drug forms acyclovir and penciclovir to acyclovir monophosphate and penciclovir monophosphate which is then acted on by human cellular-GMP kinase and other cellular kinases
True (Valacyclovir is the oral prodrug of acyclovir and Famciclovir is the oral prodrug of penciclovir)
Step 1 = viral thymidine kinase (phosphorylates acyclovir/penciclovir)
Step 2 = human cellular-GMP kinase and other cellular kinases (further phosphorylates acyclovir/penciclovir monophosphate)
Step 3 = acyclovir/penciclovir triphosphate competes with normal deoxyguanosine triphosphate for viral-DNA polymerase
Step 4 = incorporation of acyclovir/penciclovir triphosphate into viral DNA (leads to chain termination and reduced viral replication)
Human Cellular-GMP kinases and other cellular kinases covert acyclovir monophosphate or penciclovir monophosphate to either acyclovir triphosphate or penciclovir triphosphate
True
Step 1 = viral thymidine kinase (phosphorylates acyclovir/penciclovir)
Step 2 = human cellular-GMP kinase and other cellular kinases (further phosphorylates acyclovir/penciclovir monophosphate)
Step 3 = acyclovir/penciclovir triphosphate competes with normal deoxyguanosine triphosphate for viral-DNA polymerase
Step 4 = incorporation of acyclovir/penciclovir triphosphate into viral DNA (leads to chain termination and reduced viral replication)
Acyclovir triphosphate or penciclovir triphosphate competes with normal deoxyguanosine triphosphate for viral-DNA polymerase
True
Step 1 = viral thymidine kinase (phosphorylates acyclovir/penciclovir)
Step 2 = human cellular-GMP kinase and other cellular kinases (further phosphorylates acyclovir/penciclovir monophosphate)
Step 3 = acyclovir/penciclovir triphosphate competes with normal deoxyguanosine triphosphate for viral-DNA polymerase
Step 4 = incorporation of acyclovir/penciclovir triphosphate into viral DNA (leads to chain termination and reduced viral replication)
Acyclovir triphosphate and penciclovir triphosphate are much less inhibitory of human DNA polymerase
True (competes for viral-DNA polymerase)
Step 1 = viral thymidine kinase (phosphorylates acyclovir/penciclovir)
Step 2 = human cellular-GMP kinase and other cellular kinases (further phosphorylates acyclovir/penciclovir monophosphate)
Step 3 = acyclovir/penciclovir triphosphate competes with normal deoxyguanosine triphosphate for viral-DNA polymerase
Step 4 = incorporation of acyclovir/penciclovir triphosphate into viral DNA (leads to chain termination and reduced viral replication)
The incorporation of acyclovir triphosphate or penciclovir triphosphate into viral DNAa leads to chain termination with resultant reduced viral replication
True
Step 1 = viral thymidine kinase (phosphorylates acyclovir/penciclovir)
Step 2 = human cellular-GMP kinase and other cellular kinases (further phosphorylates acyclovir/penciclovir monophosphate)
Step 3 = acyclovir/penciclovir triphosphate competes with normal deoxyguanosine triphosphate for viral-DNA polymerase
Step 4 = incorporation of acyclovir/penciclovir triphosphate into viral DNA (leads to chain termination and reduced viral replication)
Famciclovir does not undergo any hepatic microsomal metabolism, but is converted to penciclovir
True
73% of penciclovir (after conversion from famciclovir) is excreted in the urine, and 27% excreted in the faeces
True (in contrast to roughly equal urine and faecal excretion for acyclovir/Valacyclovir)
Oral famciclovir has a higher bioavailability (77%) compared to acyclovir (15-30%) and Valacyclovir (55%)
True
Bioavailability as follows:
Famciclovir > Valacyclovir > Acyclovir
Penciclovir triphosphate has a much longer intracellular half life than acyclovir triphosphate
True (Famciclovir is a prodrug that is converted to Penciclovir)
Penciclovir triphosphate = 10-20 hours in HSV-infected cells and 7 hours in VZV-infected cells
Acyclovir triphosphate = <1 hours in HSV and VZV infected cells
Acyclovir is FDA approved for primary/first episode of Herpes simplex infection
True
Immunocompetent = 200mg 5 X daily for 10 days (recommended), 400mg TDS for 10 days (real world)
Immunosuppressed = 200-400mg 5 X daily for 10 days, 5mg/kg IV TDS for 7-10 days
Acyclovir is FDA approved for recurrent episodes of Herpes simplex infections
True
Immunocompetent = 200mg 5 X daily for 5 days (recommended), 400mg TDS for 5 days (real world)
Immunosuppressed = at least 400mg TDS for 7-10 days
Acyclovir is FDA approved for suppressive therapy of Herpes simplex infections
True
Immunocompetent = continuous 400mg BD
Immunosuppressed = at least 400mg BD