Antivirals Flashcards
Acyclovir
MOA: requires HSV thymidine kinase for monophosphorylation, eventually incorporated into DNA and causes chain termination and inhibition of viral DNA polymerase
DOC: HSV encephaitis
Use: HSV-1, HSV-2, VZV, EBV (but CMV is resistant)
Resistance: altered thymidine kinase, cross-resistance
SE: local irritation, HA, N/V/D; acute renal failure in IV administration
Ganciclovir
MOA: analog of acyclovir but phosphorylated by UL97
Effect: chain termination and DNA polymerase inhibitor
DOC: CMV retinitis, CMV prophylaxis in immunocopromised pt
Resistance: mutations in enzyme or target
PK: metabolized in liver, excretion via urine
SE: myeosuppression
CI: pregnancy (Category C)
Lamivudine
MOA: phosphorylated to triphosphate (active) form which inhibits HBV and HIV RT
Use: suppressive rather than curative
SE: HA, dizzy, GI sx’s
Interferons
MOA: inhibit RNA and DNA synthesis by activating protein expression that will inhibit virus infection
Use: IFN-α tx chronic HBV and HCV, IFN-β tx MS, IFN-γ tx CGD
PK: IV or subcutaneou, usually pegylated to improve t1/2
SE: flu-like sx’s, fatigue, depression, neutropenia
Drug interactions: potentiate Zidovudine induced myelosuppression
Entecavir
MOA: phosphorylated to triphosphate (active) form which competes for viral polymerase and blocks RT activity downstream
Use: suppressive rather than curative, effective in strains resistant to Lamivudine
SE: monitor after d/c in case of exacerbation of severe hepatitis
Ribavirin
Guanosine analogue
MOA: prevents viral mRNA capping, and inhibits RNA-dependent RNA polymerase (halts viral protein synthesis)
Use: in combo w/ IFN-α to tx HCV
Sofosbuvir
MOA: prodrug that inhibits NS5B RNA dependent RNA pol
Effect: stops viral replication
Use: used in combo to tx chronic HCV +/- Ribavirin
SE: CNS (HA and fatigue), muscle weakness, nausea
Peramivir PK and SE
PK: IV
SE: itching/peeling skin, chills, cough, GI pn, fever, myalgia
Protease Inhibitors
Simeprevir / Telaprevir
MOA: reversibly bind NS3 serine protease
Effect: inhibit replication
Use: tx HCV after first line tx fails, used in combo for chronic HCV
SE: itching, rash, photosensitivity, Steven-Johnsons
Cidofovir
MOA: phosphorylated by host cell kinases, inhibits viral DNA polymerase
Use: tx CMV retinitis, or HSV resistant to other drugs
PK: co-administered w/ Probenecid (blocks renal secretion so prolongs t1/2)
SE: nephrotoxicity
Trifluridine
MOA: triphosphate form incorporated into viral DNA causing fragmentation
DOC: HSV keratoconjunctivitis and recurrent epithelial keratitis
PK: topical ophthalmic ointment w/ short t1/2 (about 12 min)
SE: eye irritation
Rimantadine PK and SE
PK: metabolized before elimination in urine and does NOT cross BBB
SE: fewer probs (GI sx’s)
Zanamivir PK and SE
PK: inhaled/intranasal
SE: airway irritation avoid in asthma/COPD pt’s
Penciclovir
MOA: monophosphorylated by thymidine kinase
Use: topical tx of HSV
SE: mild erythema
Oseltamivir PK and SE
PK: PO prodrug (hydrolyzed in liver)
SE: GI discomfort, nausea
Ion Channel Blockers
Amantadine / Rimantadine MOA: block M2 membrane protein (H+ channel) which is required for viral uncoating Effect: viral uncoating inhibited Use: influenza A only Resistance: cross-resistance
Foscarnet
MOA: analog of pyrophosphate that inhibits pyrophosphate binding site on viral DNA polymerase
Use: CMV retinitis in immunocomp pt’s, acyclovir-resistant HSV, ganciclovir-resistant CMV and VZV
PK: IV only
SE: nephrotoxicity, electrolyte disturbances, (Ca2+, Mg2+, K+, PO4), anemia, genital ulcer, CNS sx’s
Resistance: point mutations in polymerase
Ledipasvir
MOA: inhibits viral phosphoprotein NS5A
Effect: stops replication, assembly and secretion
Use: in combo to tx chronic HCV +/- Ribavirin
SE: CNS (HA and fatigue), muscle weakness, nausea
Ribavirin PK and SE
PK: PO, IV or aerosolized; distribution is prolonged in RBCs
SE: dose-dependent anemia, GI and CNS sx’s
CI: pregnancy (Category X)
Amantadine PK and SE
PK: high Vd, crosses BBB, may accumulate in urine
SE: CNS (insomnia, dizziness, ataxia, hallucinations, sz)
CI: pregnancy (Category C), monitor pt’s w/ CNS conditions and in ESRD
NA Inhibitors
Oseltamivir / Peramivir / Zanamivir
MOA: inhibits sialic acid substrate for NA
Effect: inhibit viral release
Use: influenza A and B sx control 24-48h after infection w/ the virus
