Fitz - Pharm of HIV Inf Flashcards
first line Nuceloside Reverse Transcriptase Inhibitors (NRTIs)
- abacavir
- emtracitabine
- lamivudine
- tenofovir
- zidovudine > azidothymidine
first line non-NRTIs (NNRTIs)
efavirenz
what NNRTI do you want to avoid in pregnancy
efavirenz
first line HIV Protease Inhibitors (PIs)
- atazanavir
- darunavir
adjunct PI drug always used with first line PIs
ritonavir
Integrase Strand Transfer Inhibitors (IIs)
raltegravir
CCR5 angtagonist Viral Fusion Inhibitor
maraviroc
GP41 antagonist Viral Fusion Inhibitor
enfuvirtide
MC initial HIV drug regimens
2 NRTIs +
- NNRTI
- PT
- INSTI
NRTIs that penetrate CNS
- zidovudine
- azidothymidine
NNRTI that penetrates CNS
nevirapine
MOA: NRTIs
modified versions of nucleosides > causes irreversible termination of DNA elongation > inhibits HIV DNA integration into host DNA
Purine NRTIs
- abacavir
- didanosine
- tenofovir
Pyrimidine NRTIs
- lamivudine
- emtricitabine
- zidovudine
- stavudine
host enzyme that adds initial phosphate group to NRTIs
cytosine kinase
AEs: NRTIs
- lactic acidosis syndrome
- lipoatrophy, lipodystrophy
s/s of lactic acidosis syndrome
nausea, vomiting, abd pain, wt loss, fatigue, myalgia, features of hepatic dysfunction
hallmark of NRTI toxicity
mitochondrial toxicity
mechanism of mitochodiral toxicity leading to lactic acidosis syndrome
mito DNA needed for ox phos proteins > def in proteins = impaired ox phos > anaerobic glucose metabolism > lactic acidosis
“not so bad” NRTIs
- tenofovir
- lamivudine
- emtricitabine
- abacavir
worst NRTIs
didanosin > stavudine > zidovudine
AE: tenofovir
nephrotoxicity
tenofovir elimnitation
glom filtration and active tubular secretion
what NRTI should you use in a pt with kidney disease
abacavir
s/s of abacavir hypersentivity
fever, rash, GI, respiratory s/s, lethargy, malaise
avoid used of abacavir in
HLA-B*5701 genotype pts > HSN rxn
NNRTI & PI elim
hepatic - CYP450
major NRTI combo to avoid
triple nucleoside analog combinations
preferred initial dual-NRTI therapy
tenofovir/emtricitabine
preferred initial dual NRTI therapy IN PREGNANCY
zidovudine/lamivudine
dual-NRTI therapies that tx Hep B too
- tenofovir/emtricitabine
- abacavir/lamivudine
dual-NRTI therapy that runs risk of ABC HSN
abacavir/lamivudine
NNRTI to use in preganacy
nevirapine
NNRTI to use with resistant HIV strains
etravirine
NNRTI prefered in treatment-experienced HIV pts
etravirine
MOA: NNRTIs
binds and distorts reverse transcriptase enzyme stopping viral DNA assembly > less HIV DNA > doesn’t get integrated into host genome
pregnant women taking what drug should continue tx if their HIV viral load is managed?
efavirenz
hypersensitivity to NNRTIs can cause what? which one is the worst?
- steve-johnson syndrome
- nevirapime
NNRTI that induces drug-drug interactions
efavirenz
signature mutation that confirs resistance to NNRTIs
K103N
NNRTIthat has activity against HIV strains resistant to other NNRITs
etravirine
first line initial triple drug therapy NRTIs + NNRTI
tenofovir/emticitabine/efavirenz
PIs used in drug resistant HIV
- darunavir
- tiranavir
AE: indinavir
kidney stones
MOA: PIs
mimics peptide bond btwn pehnylalanine and proline at 167 and 168 to stop translation of functional proteins
role of ritonavir use with other PIs
“boosts” bioavailability of PI it’s paired with by inhibiting CYP3A4 and prolonging their T1/2
AEs: PIs
- sulfonamide HSN
- hepatotoxicity (acute)
- lipodistrophy (LT)
Preferred dual-NRTI + PI
tenofovir/emtricitabine + ataxanavir/ritonavir
Alternative dual-NRTI + PI
tenofovir/emtricitabine + lopinavir/ritonavir
post exposure prophylaxis for HIV should be started within how many days
3
3 drug PEP recommended in pregnancy
- zidovudine + lamivudine
- lopinavir + ritonavir
- 2x/d
3 drug PEP recommended w/ chance of liver toxicity
- tnofovir + enmticitabine qd
- lopinavir + ritonavir
MOA: raltegravir
inhibition of HIV intrgrase > stops integration of HIV DNA into host DNA
AEs: raltrgravir
- myopathy
- rhabdomyolysis
- skin reactions
MOA: maraviroc
blocks gp120* binding to CCR5 > prevents gp41 exposure and viral fusion
what receptor is maraviroc ineffective against
CXCR4
MOA: Enfuvirtide
blocks gp41 fusion and inhibits HIV entry into host cell