Antivirals Flashcards
HSV/ VZV- correspond to what HHVs
1,2,3
First line Tx for HSV, VZV
Acylovir, Valacyclovir, Penciclovir, Famicilovir
Alternative Tx for HSV and VZV
Cidofovir, Foscarnet, Vidarabine
Acyclovir- Drug class
Nucleoside analog
Acyclovir- MOA
viral thymidine kinase converts Acyclovir to acylco GMP –> inhibits viral DNA pol, chain termination
Acyclovir- Features
High selectivity, poor solubility and oral availability
Topical, IV, Oral- not absorbed well orally
Acyclovir MOR
viral TK or viral DNA polymerase mutation
Acyclovir t1/2
3 hr- short half life
Acyclovir AE
Acyclovir has poor solubility, ensure adequate hydration to prevent crystalluria
Valcyclovir- Structure
Ester of Acyclovir
Valcyclovir advantages
Increased water solubility increases bioavailability
Penciclovir Advantage
increases oral bioavailability, prolonged intracellular half life
Pencilovir Chain termination
Not an obligate chain terminator
Famciclovir Structure
Ester of Penciclovir
Famcilovir Advantage
More water soluble & Inc half life
Cidofovir structure
Nuleotide analog of Cytidine Monophosphate
Cidofovir activation
independent of the virus
Cidofovir MOA
viral DNA polymerase inhibitor –> chain termination
CIdofovir- Admin
IV
Cidofovir- Uses
Resistant HHV1,2,3 and CMV (HHV5)
Cidofovir AE
dose limiting renal toxicity ensure is pre hydrated with IV saline
Cidofovir + Probenacid
Give probenacid to dec renal elimination of Cidofovir
Foscarnet Structure
Pyrophosphate analog
Foscarnet MOA
binds to pyrophosphate binding site of viral DNA pol –> inhibits it
Foscarnet AE
renal toxicity, prevent via hydration
Foscarnet resistance
mutation in viral DNA polymerase
Vidarabine Structure
Adenosine analog
Vidarabine MOA
viral TK coverts it to Ara- MP –> Ara- ATP inhibits viral DNA pol BUT NOT A CHAIN TERMINATOR
VIdarabine MOR
mutation in viral DNA pol
Vidarabine uses
Topical treatment for herpes keratitis. Limited systemic value b/c of metabolic inactivation and high toxicity
Tx for CMV
Cidofovir, Ganciclovir, Valganciclovir
Ganciclovir structure
similar to acyclovir but altered to be an inhibitor of UL97
Ganciclovir Features
Poor oral bioavailability
Ganciclovir AE
myelosuppresion that is potentiated when given with Zidovudine (AZT)
Gancilovir Resistance
UL97 or DNA polymerase mutation
Valgancilovir structure
Ester of Ganciclovir
Valganciclovir advantages
Increased bioavailability compared to Ganciclovir
HBV Tx 1st line, 2nd line
1st line- Lamivudine, IFN alpha
2nd line- Adefovir
Lamivudine structure
Cytidine analog
Lamivudine MOA
NRTI + chain terminator
Lamivudine AE
fairly non toxic
Lamivudine resistance
rapid and common
Adefovir Structure
AMP nucleotide
Adefovir MOA
nucletoide RTI
Adefovir use
alternative CMV tx if resistant to lamivudine
Adefovir resistance
None up to 1 yr
Adefovir AE
Dose limiting renal toxicity
IFN alpa MOA
immune cytokine that activates non selective immunity (macrophages and NK cells) and stops replication in virally infected cells
IFN alpha AE
Feel sick- fever, flu like, injection site reactions. Bone marrow suppression
IFN alpha CI
autoimmune disease, hepatic decompensation
HCV tx- 1st line, 2nd line
1st line- IFN alpha
2nd line- add Ribavirin
IFN alpha in HCV
prophylaxis and chronic infection
Ribavirin use only with?
IFN alpha
Ribavirin structure
guanidine/ adenosine dual analog
Ribarvirin MOA
inserts itself into mRNA and causes hypermutation NOT A CHAIN TERMINATOR
Ribavirin admin
oral
Ribavirin elim
renal
Ribavirin AE
dose limiting renal toxicity b/c stored in RBC for entire 90 day life span
Ribavirin CI
Pregnancy
Influenza A tx- 1st line, 2nd line
1st line- Oseltamivir
2nd line- zanamivir, amantadine, rimantadine
Amantadine MOA
M2 blocker
Amantadine uses
only prophylactic and treatment of suspected influenza A infection
Amantadine resistance
frequent but strain dependent
Amantadine AE
Crosses BBB and is dopaminergic- agitation, hallucination, cardiac arrhythmias, death if OD
Rimantadine MOA
M2 inhibitor
Rimantadine uses
prophylaxis and Tx and influenza A infection
Rimantadine AE
GI, but less BBB penetration than amantadine so less CNS side effects
Oseltamavir Name
Tamiflu
Oseltanavir MOA
Sialic acid analog that blocks neurominidase for prophylaxis and early tx
Oseltanavir resistance
high
Oseltanavir uses
Influenza A and B
Zanamavir MOA
sialic acid analog that blocks neuriminidase for propyxlaxis and early tx
Zanamavir admin
Nasal
Zanamavir AE
respiratory toxicity- bronchospasm
Zanamvir CI
Pulmonary disease
Influenza B tx
oseltamavir and zanamavir
Acylovir, Valacyclovir, Penciclovir, Famicilovir- MOA
Nucleoside activated by viral TYR kinase, inhibit viral DNA pol–> chain termination
Valganciclovir Toxicity
Same as Gancilovir- myelosuppression potentiated by Zidovudine
Lamivudine uses
Also used for HAART