HIV Pharm Flashcards
(25 cards)
interferes with thymidine incorporation first ART drug inhibit HIV 1 & 2, HTLV 1 & 2 toxicities: bone marrow suppression skeletal m. myopathy when inhibiting mitochondrial DNA polymerase inhibition hepatic steatosis
zidovudine
interfere with thymidine incorporation
inhibit HIV 1 & 2
excreted in urine unchanged
most common serious toxicity: peripheral neuropathy
NRTI associated most strongly with lipodystrophy/fat wasting
Lactic acidoses & hepatic steatosis
stavudine (d4T)
interferes with cytosine treat with HIV 1 & 2 active against HBV low barrier to resistance if on its own co-formulated with tenofovir, superior combination long intracellular half-life excreted unchanged in urine
one of the least toxic antiretroviral drugs
prolonged use leads to hyperpigmentation esp. in palms & soles
more common in AA
emtricitabine (FTC)
interfere with cytidine incorporation
use in HIV 1 & 2 & HBV
low resistance on its own, co-formulated with tenofovir
lamivudine + doltegravir used for naive treatments with low HIV numbers
long half-life
excreted primarily unchanged in urine
one of the least toxic antiretroviral drugs
lamivudine
only guanosine analog
don’t give to HLAB5701 genotype due to fatal hypersensitivity syndrome
half-life of 21 hrs
not effective against HBV
not a CYP substrate and will be conjugated w/glucuronide for renal elimination
generally avoided in patients w/CAD
abacavir (ABC)
nucleotide reverse transcriptase inhibitor
approved for HBV
co-formulated with emtricitabine
resistance due to single substitution (K65R)
intracellular half-life 10-50 hours 1x/day dosing
excreted primarily unchanged in urine
generally well tolerated with few adverse effects
can see nephrotoxicity w/ acute tubular necrosis –> Fanconi syndrome
decreased bone mineral density
tenofovir disproxil fumarate (TDF)
nucleotide reverse transcriptase inhibitor adenosine analong
broad spectrum against viral DNA polymerases approved for HBV
resistance due to single substituion
very similar to TDF
TAF transported differently than TDF –> lower doses administered –> lower plasma concentration but –> higher intracellular concentration of tenofovir-diphosphate
less renal & bone toxicity than TDF
tenofovir alafenamide (TAF)
block strand transfer
retains its activity against viruses resistant to other drug classes
terminal elimination: 9 hrs
eliminated in urine & feces unchanged & undergoes glucuronidation
generally well tolerated:
can see immune reconstitiution syndrome
some incidence of myopathy/rhadomyolysis
excellent target since human DNA is not known to undergo excision/reintegration
raltegravir
block chromosomal integration of viral DNA
resistance can develop but has high genetic barrier to resistance
primarily metabolized by UGR1A1 glucuronidation before renal excretion
available in combinations w/ abacavir & lamivudine & rilpvirine
Toxicities similar to raltegravir
avoid in pregnancy
doultegravir
part of 1X/day fixed dose combinations of elivitegtavir, cobicistat, emtricitabine & either TAF/TDF
metabolized by CYP3A4 and needs to be boosted
elvitegravir
blocks chromosomal integration of viral DNA
resistance can develop but high genetic barrier to resistance
termination elimination half-time is 16-23 hrs
more soluble/readily absorbed than other INSTI
glucuronidated by UGT1A1 & metabolized by CYP3A4 and only affected with dual inhibitors or strong CYP3A4 inducers
only available as a fixed-dose single tablet regimen
generally well tolerated
bictegravir
1st protease inhibitor inhibit both HIV-1 &2 no longer used to huge pill burden due to its short half-life Toxicitiy: GI distress long-term --> lipodystrophy
saquinavir
often works after failure of other PI-containing regimens
Toxicities: GI distress, nausea, vomiting diarrhea
increase TAGs & cholesterol
lopinavir
non-peptic but peptide-like
treatment naive & experienced (with guidance)
doubled half-life when boosted
metabolized by CYP3A4
first choice when boosted w/ritonavir or cobicistat
Toxicities: elevated bilirubin, unconjugated hyperbilirubinemia not associated with hepatitis
fat redistribution, immune reconstitution & increased serum cholesterol
atazanavir
non-peptidic protease inhibitor
inhibt HIV 1 & 2 indicated for HIV-1
used off-label for post-exposure prophylaxis
current 1st choice PI when boosted w/ ritonavir
Toxicities: increased TAGs & cholesterol, fat redistribution/ immune reconstitution syndrome
sulfa drug hypersenstivity
darunavir
early one
Toxicities crystaluria/renal stones
indinavir
only used to block CYP3A4
boots levels of other more potent protease inhibitors
Toxicities: flushing, rash, GI upset & misc
ritonavir
not a protease inhibitor
used to boost atazanavir and darunavir
cobistat
co-formulated with tenofovir
1st NNRTI approved for once daily dosing
induce CYP3A4
Toxicities: most significant CNS toxicity/psychiatirc side effects
Was considered teratogenic
rash also common
efavirenz
still works after mutations that disrupt activity of other NNRTI
induce CYP3A4
treatment-experience HIV-1 patients
Toxicities: fat redistribution, immune reconstitution syndrome, rash common
etravirine
treatment naive w/ HIV-1
not susceptible to common mut. that renders efavirenz & nevirapine ineffective
metabolized by CYP3A4
Toxicities: more common in children & adolescents, CNS & endo issues
rilpivirine
treatment naive HIV-1 patients swtiching to stable regimens
works when resistance to efavirenz or rilpiviridine
metabolized by CYP3A4
co-formulated with lamivudine & tenofovir
decreased incidence of side effects
doraviridine
approved for HIV-1 in adults & children
long half-life
decreased level of contraceptives
induced by CYP3A4
Toxicities: rash/itching –> most common side effects
nevirapine
36 aa peptide derived from viral gp41 part that fuses w/ cell mem.
inhibit formation of 6-helix bundle critical for membrane fusion
inhibit CD4+ infection
inhibit cell to cell transmission in vitro
retains its activity against viruses resistant to other drug classes
must be administered paraenterally
Toxicity: injection site reaction
enfuvirtide
