Antiviral Agents

Question 1

acyclovir

Answer 1

• herpesvirus
• nucleoside analogue
• MOA: activation by phosphorylation by viral thymidine kinase enzyme–> competitive inhibitor of DNA polymerase–> chain termination
• use: genital and varicella zoster (oral); disseminated mucocutaneous, neonate infection, HSV encephalitis, VZV in immunocompromised (IV)
• adverse effects: nausea, headache, diarrhea, nephrotoxicity (HYDRATE!)
• resistance: mutation of thymidine kinase gene, cross-resistance w/ other antivirals

Question 2

valacyclovir (Valtrex)

Answer 2

• prodrug of acyclovir (metabolized in liver and intestines)
• greater oral bioavailability
• MOA: same as acyclovir–> inhibit DNA polymerase
• use: primary/recurrent genital herpes, varicella in older children and adults, zoster, orolabial herpes
• adverse effects: nausea, headache, vomiting, rash

Question 3

foscarnet

Answer 3

• analogue of pyrophosphate
• MOA: binds site where pyrophosphate resides–> inhibits DNA polymerase
• does NOT require prior phosphorylation
• use: IV for HSV and VZV (resistant to acyclovir), CMV retinitis, CMV colitis, CMV esophagitis
• adverse effects: renal impairment, changes in Ca phosphate K or Mg, avoid use w/ nephrotoxic drugs
• resistance: rare, mutations in DNA polymerase

Question 4

ganciclovir

Answer 4

• herpes antiviral
• acyclic guanosine analogue
• MOA: phosphorylation by CMV UL97–> competitive inhibitor of viral DNA polymerase–> chain termination
• use: (IV) CMV retinitis, colitis, pneumonitis, esophagitis, reduce risk of CMV in transplant pts
• adverse effects: myelosuppression, CNS toxicity
• resistance: mutation of UL97 gene, cross-resistance with other antivirals

Question 5

valganciclovir

Answer 5

• herpes antiviral
• prodrug of ganciclovir (activated in liver and intestines)
• MOA: same as ganciclovir (DNA polymerase inhibitor)
• use: (oral) CMV retinitis (AIDS), prevention of CMV in transplant pts
• adverse effects: myelosuppression, headache, nausea, diarrhea
• resistance: UL97 mutation

Question 6

trifluridien

Answer 6

• fluorinated nucleoside
• MOA: phosphorylated by cellular enzyme–> competitive inhibitor of thymidine
• ocular admin
• keratoconjunctivitis, recurrent epithelial keratitis (HSV-1 and 2)

Question 7

oseltamivir (Tamiflu)

Answer 7

• sialic acid analogue
• MOA: activated by hepatic esterases–>binds active site of neuraminidase–> inhibits function–> inhibits spread of progeny virons through RT
• use: >1yo with influenza A and B, chemoprophylaxis, 48 hrs w/in symptoms
• adverse effects: nausea, vomiting, headache, diarrhea, rash
• resistance: point mutations in hemagglutinin or neuraminidase

Question 8

zanamivir

Answer 8

• sialic acid analogue
• MOA: activated by hepatic esterases–>binds active site of neuraminidase–> inhibits function–> inhibits spread of progeny virons through RT
• use: 7 yo

Question 9

peramivir

Answer 9

• MOA: neuraminidase inhibitor
• use: acute, influenza symptoms for no more than 48 hrs
• IV admin
• adverse effects: GI effects, rash, Steven Johnson syndrome, hyperglycemia, hypertension, delirium

Question 10

amantadine

rimantadine

Answer 10

• symmetric tricyclic amines
• MOA: inhibit influenza A M2 protein–> inhibits necleocapsid release
• use: Influenza A, w/in 48 hrs of symptoms
• adverse effects: nausea, anorexia, neurological symptoms
• resistance: high levels, aa substitution in M2

Question 11

ribavirin

Answer 11

• guanosine analogue
• MOA: phosphorylated by cellular adenosine kinase–> interferes with synthesis of guanosine triphosphate–> inhibit viral mRNA capping–> inhibit RdRp of RSV and HCV
• use: RSV bronchitis,combo therapy for HCV
• aerosol admin (RSV), oral admin (HCV)
• adverse effects: hemolytic anemia, depression, rash, cough, insomnia
• contraindications: pregnancy, anemia, ischemic vascular disease, severe renal disease

Question 12

paritaprevir

Answer 12

• HCV protease inhibitor
• MOA: inhibit HCV NS3/4A protease–> inhibit proteolysis cleavage of immature viral polypeptides into mature viral proteins
• oral admin, combo w/ ombitasvir and ritonavir
• use: chronic HCV
• adverse effects: asthenia, fatigue, nausea, insomnia
• resistance: NS3 gene substitituions

Question 13

simeprevir

Answer 13

• HCV protease inhibitor
• MOA: inhibit HCV NS3/4A protease–> inhibit proteolysis cleavage of immature viral polypeptides into mature viral proteins
• oral admin, combo w/ sofosbuvir, or ribavirin and pegylated interferon
• use: chronic HCV (screen pts for NS3 Q80K polymorphism)
• adverse effects: rash, pruritus, dyspena, nausea, myalgia
• resistance: NS3 gene substitution

Question 14

ledipasvir

Answer 14

• nucleotide analogue HCV NS5A inhibitor
• MOA: inhibit NS54 protein–> inhibit viral RNA replication and virion assembly
• oral admin, combo w/ sofosbuvir
• use: chronic HCV
• adverse effects: diarrhea, fatigue, headache, hyperbilirubinemia, nausea, insomnia
• resistance: NS5A gene substitution

Question 15

ombitasvir

Answer 15

• nucleotide analogue HCV NS5A inhibitor
• MOA: inhibit NS54 protein–> inhibit viral RNA replication and virion assembly
• oral admin, combo w/ paritaprevir and ritonavir
• use: chronic HCV
• adverse effects: asthenia, fatigue, nausea, insomnia
• resistance: NS5A gene substitution

Question 16

sofosbuvir

Answer 16

• RNA polymerase inhibitor-nucleotide analogue
• MOA: prodrug–> incorporated into RNA by RNA-dependent-RNA polymerase–> premature chain termination
• oral admin, avoid coadmin w/ potent inducers of p-glycoprotein
• use: chronic HCV, used in combo w/ ledipasvir (Harvoni)
• adverse effects: anemia, fatigue, headache, insomnia, nausea, flu like symptoms
• resistance: rapid–> monotherapy NOT recommended

Question 17

dasabuvir

Answer 17

• RNA polymerase inhibitor, non-nucloside inhibitor
• MOA: target palm domain of RNA by RNA-dependent-RNA polymerase–> halt viral life cycle
• oral admin, combo w/ ombitasvir, paritaprevir, ritonavir
• use: chronic HCV
• adverse effects: fatigue, asthenia, insomnia
• resistance: rapid–> monotherapy NOT recommended

Question 18

abacavir

Answer 18

• nucleoside reverse transcriptase inhibitor (NRTIs), guanosine analogue
• MOA: phosphorylated–> competitively inhibit reverse transcriptase enzyme
• use: naive and experienced HIV, oral admin
• adverse effects: allergic rxn (screen for HLA-B5707), rash, fever, nausea, vomiting, pancreatitis, cardiac events
• lowers effects of methodone
• resistance: mutation in HIV reverse transcriptase gene

Question 19

lamivudine

Answer 19

• nucleoside reverse transcriptase inhibitor (NRTIs), cytosine analogue
• MOA: phosphorylated–> competitively inhibit reverse transcriptase enzyme
• use: naive and experienced HIV, oral admin, pregnant mothers and neonates, chronic HBV
• adverse effects: least toxic antiretroviral, high doses–>GI and CNS
• resistance: single base change

Question 20

emtricitabine

Answer 20

• nucleoside reverse transcriptase inhibitor (NRTIs), fluorinated analogue of lamivudine
• MOA: phosphorylated–> competitively inhibit reverse transcriptase enzyme
• use: naive and experienced HIV, oral admin
• contraindication: pregnant mothers and neonates, renal or hepatic failure
• adverse effects: headache, nausea, diarrhea, rash, hyperpigmentation of palms and soles
• resistance: single base change

Question 21

tenofovir

Answer 21

• nucleoside reverse transcriptase inhibitor (NRTIs), adenosine analogue
• MOA: phosphorylated–> competitively inhibit reverse transcriptase enzyme
• oral admin., poorly soluble
• use: naive and experienced HIV, reduces transmission, chronic HBV
• adverse effects: GI discomfort, headache, asthenia, renal/bone toxicity, crosses placental (decreases fetal growth)
• resistance: single codon change

Question 22

zidovudine (AZT)

Answer 22

• nucleoside reverse transcriptase inhibitor (NRTIs), deoxythymidine analogue
• MOA: phosphorylated–> competitively inhibit reverse transcriptase enzyme
• use: naive and experienced HIV, oral admin, reduce vertical transmission, post exposure prophylaxis
• adverse effects: myelosuppression, fatigue, malaise, nausea, headache, insomnia, asthenia, nail hyperpigmentation
• resistance: multiple mutations in HIV reverse transcriptase gene

Question 23

efavirenz

Answer 23

• non-nucleoside reverse transcriptase inhibitor (NNRTIs)
• MOA: bind reverse transcriptase district from active site
• do NOT require phosphorylation
• NOT active against HIV-2
• use: naive and experienced HIV
• contraindicated: during pregnancy
• adverse effects: CNS effects, rash, increased liver enzymes, headache, nausea, tertogenic, induces cytochrome P450
• resistance: single base change

Question 24

nevirapine

Answer 24

• non-nucleoside reverse transcriptase inhibitor (NNRTIs)
• MOA: bind reverse transcriptase district from active site
• do NOT require phosphorylation
• NOT active against HIV-2
• use: naive and experienced HIV, prevent vertical transmission
• adverse effects: rash, hepatitis, nausea, headache
• resistance: single base change

Question 25

atazanavir

Answer 25

- protease inhibitor - MOA: mimic peptide targets-->inhibit HIV protease--> block maturation of virion particles after budding - oral admin, requires acid for absorption - use: naive and experienced HIV, 6yo

Question 26

ritonavir

Answer 26

- protease inhibitor - MOA: mimic peptide targets-->inhibit HIV protease--> block maturation of virion particles after budding - oral admin - use: not used as sole PI in regimen, used as "booster" to increase half-life of ARV drugs - adverse effects: nausea, diarrhea, paresthesias, heptatis, lipodystrophy POTENT inhibitor of cytochrome P450 - resistance: multiple mutations

Question 27

darunavir

Answer 27

- protease inhibitor - MOA: mimic peptide targets-->inhibit HIV protease--> block maturation of virion particles after budding - oral admin, coadmin. w/ enhancers (ritonavir) - use: naive and experienced HIV - adverse effects: diarrhea, headache, nausea, rash, hyperlipidemia, increase liver enzymes and serum amylase - resistance: few

Question 28

maraviroc

Answer 28

- CCR5 receptor antagonist - MOA: bind cellular CCR5 protein--> prevent interaction with gp120 envelop--> stop virion from entering cell - oral admin., substrate of CYP34A - use: CCR5 tropic HIV virus - adverse effect: cough, URT infection, postural hypotension, arthralgia, myalgia, allergic reaction, increased cardiac events - resistance: change in tropism or mutation in gp120

Question 29

enfuvirtide

Answer 29

- fusion inhibitor - MOA: binds gp41 fusion protein--> prevent conformational change for fusion of viral envelop with plasma membrane--> prevent nucleocapsid from reaching interior cell - ONLY parenterally admin - use: experience HIV w/ evidence of HIV replication even w/ ARV tx - adverse effects: painful erythematous nodule at site of injection, insomnia, headache, allergy, eosinophilia - resistance: high requires multiple mutations in gp41 gene

Question 30

raltegravir

Answer 30

- integrase inhibitor - MOA: inhibit integrase--> inhibit incorporation of linear HIV DNA into host genome--> prevent formation of provirus - oral admin - use: experienced and naive HIV - adverse effects: insomnia, headache, diarrhea, nausea, dizziness, fatigue, myopathy, rhabdomyolysis - resistance: single mutation in integrase gene

Question 31

elvitegravir

Answer 31

- integrase inhibitor - MOA: inhibit integrase--> inhibit incorporation of linear HIV DNA into host genome--> prevent formation of provirus - oral admin, requires coadmin w/ ritonavir - use: experienced and naive HIV - adverse effects: nausea, diarrhea, elevation of lipase, headache, fatigue, insomnia, depression, rash - resistance: single mutation in integrase gene

Question 32

dolutegravir

Answer 32

- integrase inhibitor - MOA: inhibit integrase--> inhibit incorporation of linear HIV DNA into host genome--> prevent formation of provirus - oral admin - use: HIV pts 12 yo

Question 33

ARV therapy

Answer 33

- 1 PI (ritonavir boosted) + 2 NRTIs | - 1 II + 2 NRTIs