HIV drugs 12/17 Flashcards
fusion inhibitors
enfuvirtide/fuzeon
binds gp41 (not yet part of recommended regimen)
subq–> site Rx, increased bacterial pneumonia,hypersens
CCR5 antagonist
maraviroc
works only against HIV that is CCR5-tropic (early phase)
AE:cough,fever,rash,URI,abd pain,dizziness
Hepatoxicity
metabolized by CYP450
integrase inhibitor
raltegravir
used in combination with 2 NRTI in initial tx
rifampin enhances elimination via enhanced glucuronidation
antacids may bind with it and inhibits action
minor AE
Nucleoside analogues RTI (NRTI)
zidovudine(AZT),lamivudine(3TC),emtricitabine,abacavir
first line therapy for AIDS
phosphorylated by host kinases–> RT more susceptible to inhibitory effect than mammalian DNA polymerase
also causes chain termination of DNA as it is being transcribed from RNA
mitochondrial toxicity and lactic acidosis
specific for NRTI
DNA polymerase of mito sensitive to these drugs
more mito in a cell–> more AE
pancreatitis,peripheral neuropathy,myopathy,cardiomyopathy,hepatic steatosis,lipid dystrophy
cause of zidovudine induced anemia and neutropenia
Abacavir causes hypersens Rx
not related to mito toxicity
related to gene variant HLA-B5701
pharmacokinetics of NRTI
excreted in kidney–> adjust dose for renal impairment
CYP450 inhibitors (cimetidine)–> increase dose of NRTI
CYP450 inducers (rifampin)–> decrease NRTI
probenicid increases NRTI
some drugs have additive toxicity
some compete for common activating kinases (don’t give together)
nucleotide analogues
tenofovir
do not need to be phosphorylated
no reported mito toxicity
weakness,headache,diarrhea
non-nucleoside RTI (NNRTI)
efavirenz,delavirdine,nevirapine
no interaction with active site of RT,other mechanism
can be combined with NRTI
specific AE of NNRTI
rash: Steven-johnson syndrome with nevirapine
hepatitis: nevirapine.occure early in therapy
inducers of CYP450
Efavirenz teratogenic in animals.Also CNS AE so don’t give to pts with mental illness
protease inhibitors
ritonavir,lopinavir,amprenavir
HIV contains aspartate protease that contains dipeptide structure not seen in other mammalian proteins
PI target this dipeptide region
specific AE of PI
most cause GI tolerance,n/v/d
hyperglycemia–> new onset DM
lipodystrophy: central obesity and peripheral fat wasting,cushingoid appearance.fat atrophy due to mito toxicity of NRTI and fat accumulation due to hyperlipidemia and insulin resistence by PI
hyperlipidemia: ritonavir
hepatoxicity: can occure at any point during therapy unlike nevirapine
osteonecrosis,osteopenia,osteoporosis:pts with long term HAART(highly active antiretroviral therapy) and PI
PI and CYP450
substrate and inhibitor–> drug/drug interaction
PI boosting
lopinavir/ritonavir
utilizes the ability of ritonavir to inhibit CYP450 to enhance action of other PI’s
NNRTI based regimen
efavirenz+tenofovir/emtricitabine or zidovudine/lamivudine
except in pregnancy
