Antivirals Flashcards
enfuvirtide
HIV antiviral- entry inhibitor (fusion)
- peptide inhibitor that binds to the gp41 subunit
- prevents conformational change required for fusion
- administered sub-q
- genetic resistance d/t mutations in gp41
- no cross-resistance, limited s/fx
maraviroc
HIV antiviral- entry inhibitor (CCR5 Binding)
- binds to host protein CCR5
- used for CCR5-tropic (R5) HIV-1 infection after virologic failure
- resistance d/t mutations in gp120
- no cross-resistance with other antiretrovirals
- contraindicated with strong CYP3A4 inhibitors
abacavir
HIV antiviral- NRT inhibitor
- inhibitors of viral reverse transcriptase (RT)
- compete with doxynucletide substrates in binding to the polymerase
- incorporated analog causes chain termination
- prodrugs that are activated by conversion to nucleotide triphosphate from cellular enzymes
- high level of resistance requires mult. RT mutations
- guanosine analog
- combination formulations: abacavir-lamivudine
lamivudine
HIV antiviral- NRT inhibitor
- inhibitors of viral reverse transcriptase (RT)
- compete with doxynucletide substrates in binding to the polymerase
- incorporated analog causes chain termination
- prodrugs that are activated by conversion to nucleotide triphophate from cellular enzymes
- cytosine analog
- synergizes with many antiretroviral NRTIs
- combination formulations: abacavir-lamivudine
efavirenz
HIV antiviral- NNRT inhibitors
-inhibit retroviral RT activity
++binding site of NNRTIs is distinct from NRTIs
++allosteric inhibitors (do not compete with nucleoside triphosphate nor require phosphorylation)
-primary resistance significant mandating prior genotyping of HIV
++some mutations causes resistance across class but no cross-resistance with NRTIs
-metabolized by CYP3A4
-S/Fx: GI disturbances and Stevens-Johnson syndrome
-Specific:
++long half-life
++numerous CNS symptoms varying from mild to severe psychiatric
++fetal abnormalities so avoid in pregnancy
nevirapine
HIV antiviral- NNRT inhibitors
-inhibit retroviral RT activity
++binding site of NNRTIs is distinct from NRTIs
++allosteric inhibitors (do not compete with nucleoside triphosphate nor require phosphorylation)
-primary resistance significant mandating prior genotyping of HIV
++some mutations causes resistance across class but no cross-resistance with NRTIs
-Specifics:
++inducer of CYP3A4 (lowers methadone levels)
++effective in prevention of transmission of HIV from mother to newborn
ritonavir
HIV antiviral- protease inhibitor
-leads to production of immature, non-infectious viral particles
-do not require phosphorylation
-resistance due to mutation of viral protease gene
-can cause hyperglycemia and insulin resistance
-inhibits CYP3A4 which may be used to enhance concentration of other retrovirals resulting in synergy (booster therapy)
-Specific:
++metabolize to active compound via CYPs
saquinavir
HIV antiviral- protease inhibitor
-leads to production of immature, non-infectious viral particles
-do not require phosphorylation
-resistance due to mutation of viral protease gene
-can cause hyperglycemia and insulin resistance
-inhibits CYP3A4 which may be used to enhance concentration of other retrovirals resulting in synergy (booster therapy)
-Specifics:
++short half-life, low oral bioavailability
++once daily dose of saquinavir-ritonavir (booster therapy)
++reduced GI disturbances but combo can lead to cardiac toxicity
dolutegravir
HIV antiviral- integrase inhibitor
-block integration of viral DNA into host genome
++bind/inhibit viral integrase enzyme
++resistance by integrase gene mutations
-newly approved for tx-naive, tx-experienced HIV-infected
-adverse effects: allergy, abnormal liver function in pts with HVB and HVC
-pharmacokinetics altered by drugs that alter drug metabolizing enzymes
acyclovir
Guanosine analog
-competes with dGTP in binding to DNA polymerase (inhibition), and produces chain termination of the viral DNA.
-Activated by HSV thymidine kinase (HSV-TK). This shows selectivity because human cells lack this enzyme.
-Use: HSV (especially 2), VZV, and some CMV
+helps reduce lesions 2/2 varicella (chicken pox) if given within 24’
+helps with lesions 2/2 shingles if given within 72’.
-S/E: HA, nausea, diarrhea.
-cross-resistance is common.
valacyclovir
Guanosine analog
-Prodrug of acyclovir with better PO BioAV
+ once converted to acyclovir the MOA is similar.
-shorter DOA than acyclovir
-competes with dGTP in binding to DNA polymerase (inhibition), and produces chain termination of the viral DNA.
-Activated by HSV thymidine kinase (HSV-TK). This shows selectivity because human cells lack this enzyme.
-Use: HSV (especially 2), VZV, and CMV prevention following transplant
cidofovir
Cytosine NUCLEOTIDE analog
-inhibit DNA polymerase.
-does not require kinase activation.
-Use: CMV and HSV 1 & 2.
-S/E: dose dependent proximal tubular nephrotoxicity
+Co-administer with probenecid will inhibit tubular secretion of cidofovir metabolites (decreasing toxicity).
docosanol
long chain saturated alcohol
- Use: tx of HSV and VZV
- blocks fusion of viral and cellular membranes.
- topical only: oralabial herpes (HSV-1).
foscarnet
Inorganic pyrophosphate analog (phosphonoformic acid).
-inhibit DNA polymerases of herpes viruses, RNA polymerases, and HIV RT.
-Effective against several viruses.
+good for viruses that are resistant to ganciclovir, acyclovir, and cidofovir.
-IV use only (poor BioAv)
-S/E: renal impairment (check CrCl to determine dosing).
ganciclovir
Nucleoside Anaglog
-similar MOA to acyclovir, and metabolic activation to nucleoside monophosphate requires CMV kinase UL97.
-Use: CMV (major use), HSV, VZV, and EBV
-resistance occurs via mutation of CMV kinase gene, and DNA polymerase gene (UL54).
+good for CMV when immunosuppression is present.
-S/E: most common is myelosuppression
