All Lectures: Integrase Inhibitors

function of integrase

integrates viral DNA into the DNA of the host cell

why is ssRNA positive

bc it is the sense strand, so it is the same after transcription has occurred

how big is HIV DNA

9700 bases

p17 codes for

matrix of HIV

p24 codes for

capsid

p7 codes for

nucelocapsid

p10 codes for

protease

what is this drug

raltegravir

what is this highlighted structure of raltegravir

oxadiazole

what is the highlighted structure on raltegravir?

catalytic and metal chelating scaffolding

what is the highlighted structure on raltegravir?

hydrophobic binding site for enzyme binding

Raltegravir adult dosing

400 or 600 mg BID

Take with or without food

Raltegravir ADE

Very few

Potential myopathies

Rhabdomyolysis (monitor CPK)

Raltegravir pediatric formulations

Oral suspension and flavored chew tablets

Raltegravir pediatric dosing

weight based (only if < 55 lbs)

Raltegravir might be pref if the person has a high risk of ____

CV issues

what drug is this?

elvitegravir

metabolism of elvitegravir

primarily oxidative metabolism via CYP3A,

secondarily glucuronidated via UGT1A1/3 enzymes

what conc of elvitegravir metabolites are found in the plasma?

low conc

______inducers reduce Elvitegravir concentrations in the body, potentially triggering the development of resistant virus strains.

CYP3A4

CYP3A inducers _____ Elvitegravir concentrations in the body, potentially triggering the development of resistant virus strains.

reduce

what are some strong CYP3A4 inducers

rifampicin, the anticonvulsants carbamazepine, phenobarbital and phenytoin

what is this highlighted structure of elvitegravir?

hydrophobic region for enzyme binding

what is this highlighted structure of elvitegravir?

catalytic and metal chelating scaffold

dosing of DTG in pts who are naive

50 mg qd

dosing of DTG in experienced pts

50 mg BID

dosing of DTG for pts who weigh b/t 66-88 kg

35 mg qd

DTG ADE

Insomnia and HA

DTG must be taken 2 hours before or 6 hours after which drugs?

-          cation containing antacids or laxatives

-          Sucralfate

-          Iron or calcium supplements

-          Buffered medications

DTG may work in ots who are resistant to ___

other INSTIs (only if taken BID tho)

Pts attempting to become preg might want to take which INSTI over others?

dolutegravir

DTG is assoc with ___ in naive pts

weight gain

what generation of HIV integrase inhibitors is dolutegravir?

second gen

what drug is this?

Dolutegravir DTG

how is Dolutegravir DTG’s cross resistance?

limited

DTG is able to inhibit strands that are resistant to…

RAL and EVG

Dolutegravir is a part of the combo pill Triumeq, what are the other two medications in this pill?

ABC and 3TC