Antiviral Flashcards
Oseltamivir, Zanamivir:
MOA
Clinical Use
Administration
Inhib Flu Neuraminidase–>decrease release of progeny virus (DOESN’T KILL VIRUS)
- Flu A&B treatment/prevention
* given within 48hrs of Symptoms (F/myalgias)
Acyclovir, famciclovir, valacyclovir (prodrug):
MOA
MOResistance
Guanosine Analogs
RXN: Guanine –> Guanine-P –> Guanine-PPP
1. monophosphorylation occurs via HSV/VZV thymidine kinase
2. Triphosphate formed by cellular enzymes
3. preferentially inhib viral DNA polymerase by chain termination
- phophorylation will only take place in uninfected cells–> few adverse cells
Resistance: Mutated viral thymidine kinase
Acyclovir, famciclovir, valacyclovir (prodrug): Clinical use(3)
Acute/reactivation HSV, VZV, EBV (weak)
- HSV mucocutaneous/genital lesion
- HSV encephalitis
- Px: immunocompromised patients
- NOT FOR LATENT FORMS OF HSV/VZV
- Valacyclovir=prodrug–>better oral bioavailability
Drug used to treat Herpes Zosters
famciclovir
Acyclovir, famciclovir, valacyclovir (prodrug):
Adverse
How to avoid adverse?
- obstructive crystalline nephropathy
- Acute Renal Failure
- Make sure patient stays HYDRATED
Ganciclovir, Valganciclovir (prodrug):
MOA
MOResistance
Guanosine analog
Guanosine Analogs
RXN: Guanine –> Guanine-P –> Guanine-PPP
1. monophosphorylation occurs via CMV viral kinase
2. Triphosphate formed by cellular enzymes
3. preferentially inhib viral DNA polymerase by chain termination
Resistance: mutated viral kinase
CMV types of infections in immunocompromised (3)
- CMV colitis
- CMV retinitis
- CMV esophagitis
Ganciclovir, Valganciclovir (prodrug):
Clinical Use
- CMV, esp in immunocompromised patients
2. Valganciclovir=prodrug–> better oral bioavailability
Ganciclovir, Valganciclovir (prodrug):
Adverse
Compare toxicity of ganciclovir w/ acyclovir
- Bone Marrow Suppression (leukopenia, neutropenia, thrombocytopenia)
- Renal tox
toxicity: ganciclovir > acyclovir
CMV details: Histo Latent in which cells infections transmission:
Histo: owl’s eye inclusions
* latent in mononuclear cells
- congenital infection (TORCH)
- Mono (monospot -)
- pneumonia
- retinitis
-congenital, transfusion/transplant, sex, saliva, urine
Foscarnet:
MOA
MOResistance
Pyrophosphate analog (“pyro’FOS’phate”)
- ->binds pyrophosphate-binding site of enzyme
1. viral DNA/RNA polymerase inhib
2. HIV reverse transcriptase inhib - does not require any kinase activation
Resistance: Mutated DNA polymerase
Foscarnet:
Clinical use
2nd line for CMV/ HSV
- CMV retinitis in immunocomp. pt. when ganciclovir fails
- acyclovir-resistant HSV
*can be used when resistance develops to ganciclovir/acyclovir b/c Foscarnet doesn’t require any kinase activation
Foscarnet:
Adverse
- Nephrotox –>electrolyte abn (+/- Ca+2, +/- Phosphate, hypokalemia, hypomagnesemia)
- seizures (from electrolyte imbalance)
Which B-lactam Abx can cause seizures?
Carbapenems
Drugs which induce seizures
“With seizures, I BItE my tongue”
- Isoniazid (B6 def)
- Buproprion
- Imipenem/cilastatin
- Enflurane
- Foscarnet(from nephrotox)
Cidofovir:
MOA
Half-life?
inhib viral DNA polymerase
-DOESN’T REQUIRE VIRAL KINASE PHOSPHORYLATION
-long half-life
Cidofovir: Clinical use (2)
- CMV retinits in immunocompromised patients
2. acyclovir-resistant HSV
Cidofovir:
Adverse
How to decrease toxicity?
Nephrotox
coadmin w/ Probenecid + IV saline
Compare Foscarnet vs. Cidofovir:
MOA
Clinical Use
Adverse
Foscarnet: inhib both RNA/DNA pol & HIV RT
Cidofovir: inhib only DNA pol
- both second line only
- both cause Nephrotox
What is HAART?
When does it begin
Describe regimen
“highly active antiretroviral therapy”
-often initiated at time of HIV diagnosis. Strongest indication for patients presenting with AIDS-defining illness, low CD4+ cell counts (
NRTIs:
Name (7)
Nucleoside RT inhib.
- Abacavir (ABC)
- Didanosine (ddl)
- Emtricitibine (FTC)
- LamiVUDINE (3TC)
- StaVUDINE (d4T)
- Tenofovir (TDF)
- ZidoVUDINE (ZDV)
“haVE U DINED (VUDINE) with my NUCLEAR (NUCLEOSIDE) family?”
NRTIs:
MOA
Competitively inhib Nucleotide binding to RT and terminate the DNA chain (lack 3’OH group)
*Require Phosphorylation to be active!
Unique characteristic of Tenofovir
‘T’enofovir is a nucleo’T’ide–> doesn’t require phosphorylation to become active
2 uses Zidovudine
- general prophylaxis
2. during pregnancy to decrease risk of fetal transmission
Who is Abacavir contraindicated in?
pt with HLA-B*5701 mutation
NRTIs:
Adverse
How to decrease/overcome toxicity
- Bone Marrow suppression (reverse w/ G-CSF or EPO)
- peripheral neuropathy
- lactic acidosis (nucleosides)
- anemia (ZDV)
- pancreatitis (didanosine)
NNRTIs:
Name 3
Non-nucleoside RT inhib
- Delavirdine
- Efavirenz
- Nevirapine
NNRTIs:
MOA
Bind Reverse Transcriptase at different site than NRTI
*don’t require phosphorylation to be active
NNRTIs:
Common adverse for all?
- Rash
2. Hepatotox (Allman taught not to start this class unless CD4 count was significantly low)
NNRTIs:
Which causes vivid dreams and CNS symptoms?
Efaviren’Z’
*efaviren’z’ gives you cra’z’y ‘zzz’s’