All Lectures: NNRTIs

Su, Shah, horace (no combo drugs)

name the non-nucleoside RT inhibitors

Nevirapine, Delavirdine, Efavirenz, Etravirine, Rilpivirine

(NEEDR)

NNRTI can be used with NRTIs to have ___ activity

synergistic

combo NNRTI and NRTI use can lead to…

decrease viral load and increases CD4 cells

Nevirapine and its analogues have antiretroviral activity against _____ resistant HIV strains.

AZT

Nevirapine and its analogues have antiretroviral activity against _____

AZT resistant HIV strains

Nevirapine binds directly to reverse transcriptase to …

blocks RNA/DNA-dependent polymerase activity

Nevirapine does not compete with _____ for DNA replication

nucleotides

Nevirapine is taken…

orally

Nevirapine is metabolized as a _____, and is excreted in the ____

glucuronide conjugate; urine

Nevirapine ADE

Might cause: rash, stevens johnson syndrome or toxic epidermal necrosis

nevirapine is an ____ of CYP450s

inducer

why cant you co-admin NVP with ATV?

it will decrease ATV conc and increase NVP conc

NVP + ____ will lead to an increase in NVP conc and a decrease in the conc of the other drug

Atazanavir (ATV)

NVP + ____ will require dosing adjustments

lopinavir/ritonavir

dosing adjustments for NVP + lopinavir/ritonavir

Use lopinavir/ritonavir 500/125 mg bid tablet or 533/122 mg bid liquid

which drug is used for infants who are < 14 days old and < 2 kg?

nevirapine

nevirapine can be used on infants who are ____ old

< 14 days

what drug is this

Nevirapine

Delavirdine works on which type of HIV

HIV 1

Delavirdine inhibits the activity of ____

DNA/RNA polymerase

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Delavirdine has synergistic effects when used with which drugs

ddl, ddC, or AZT (ZDV)

Delavirdine is beneficial in ____ HIV infection

early

Delavirdine is taken via ___; ___ food

oral (with or without food)

Delavirdine is metabolized to ___ in the ____

N-des-isopropyl metabolite; liver

Delavirdine ADE

Nausea, dizziness, headache, fatigue, diarrhea

Delavirdine dosing

100 mg daily

Delavirdine is often used in pts who are resistant to ____-

other NNRTIs

Delavirdine has less drug interactions than…

efavirenz and rilpivirine

what drug is this

delavirdine

which drug is this

efavirenz

what is the chemical name for efavirenz

(4S)-6-Chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one

where is the chiral center on efavirenz

efavirenz is a RT inhibitor of which types of HIV

wild type and resistant mutants HIV1

efavirenz metabolites that must go through glucuronidation via UGT to be eliminated from the body

8-hydroxyefavirenz

8,14-hydroxyefavirenz

7-hydroxyefavirenz

7,8-hydroxyefavirenz

which metabolites of efavirenz are neurotoxic

7-hydroxyefavirenz

8-hydroxyefavirenz

what do the neurotoxic metabolites of efavirenz do

activate CYP46A1 cand cause neurotoxicity’s of mitochondrial damage and inflammation

efavirenz is a ____ of CYP450

inducer and inhibitor

efavirenz ADE

Might cause rash, stevens Johnson syndrome or toxic epidermal necrosis

efavirenz + ATV leads to ____ conc of ATV

decreased

efavirenz + ATV doing adjustments for naive pts

ATV 400 mg with ritonavir

efavirenz should not be co-admin with ____

ATV

efavirenz + lopinavir / ritonavir leads to _____ lopinavir/ritonavir conc

decreased

dosing adjustment of lopinavir/ritonavir if used with efavirenz

500/125 mg bid tablet or 533/122 mg bid liquid

efavirenz + maraviroic leads to _____ maraviroic conc

decreased

dosing adjustment of maraviroc if used with efavirenz

Increase the maraviroc level to 600 mg bid

etravirine is very ____ due to its single bonds

flexible

what metabolite of efavirenz is this

7-hydroxyefavirenz

what metabolite of efavirenz is this

8-hydroxyefavirenz

what metabolite of efavirenz is this

7,8-hydroxyefavirenz

what metabolite of efavirenz is this

8,14-hydroxyefavirenz

the major metabolites of ertavirine are formed via which reaction

benzylic methyl hydroxylation of the dimethylbenzonitrile moiety

what drug is this

Etravirine

Etravirine works on strands that are resistant to ____

nevirapine and efavirenz

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