Antiviral Agents Flashcards
1
Q
acyclovir
A
- 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
2
Q
valacyclovir (Valtrex)
A
- 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
3
Q
foscarnet
A
- 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
4
Q
ganciclovir
A
- 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
5
Q
valganciclovir
A
- 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
6
Q
trifluridien
A
- fluorinated nucleoside
- MOA: phosphorylated by cellular enzyme–> competitive inhibitor of thymidine
- ocular admin
- keratoconjunctivitis, recurrent epithelial keratitis (HSV-1 and 2)
7
Q
oseltamivir (Tamiflu)
A
- 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
8
Q
zanamivir
A
- 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
9
Q
peramivir
A
- 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
10
Q
amantadine
rimantadine
A
- 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
11
Q
ribavirin
A
- 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
12
Q
paritaprevir
A
- 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
13
Q
simeprevir
A
- 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
14
Q
ledipasvir
A
- 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
15
Q
ombitasvir
A
- 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
16
Q
sofosbuvir
A
- 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
17
Q
dasabuvir
A
- 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
18
Q
abacavir
A
- 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
19
Q
lamivudine
A
- 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
20
Q
emtricitabine
A
- 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
21
Q
tenofovir
A
- 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
22
Q
zidovudine (AZT)
A
- 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
23
Q
efavirenz
A
- 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
24
Q
nevirapine
A
- 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
25
Q
atazanavir
A
- 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
26
Q
ritonavir
A
- 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
27
Q
darunavir
A
- 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
28
Q
maraviroc
A
- 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
29
Q
enfuvirtide
A
- 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
30
Q
raltegravir
A
- 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
31
Q
elvitegravir
A
- 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
32
Q
dolutegravir
A
- 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
33
Q
ARV therapy
A
- 1 PI (ritonavir boosted) + 2 NRTIs
- 1 II + 2 NRTIs