PHRM 865 Exam 4 Study Guide
Replication cycle of HIV - ANSWER Attachment and fusion
Nucleocapsid released
Reverse transcription
Integration of DNA into nucleus
Viral RNA created
Budding and release
Protease cleaves to release HIV particles to other cells
How are NRTI's activated? - ANSWER All NRTI's are prodrugs that are activated after
being phosphorylation *3 times*
TDF vs TAF: cleavage - ANSWER TDF: plasma esterases
TAF: cellular esterases
How is Tenfovir different from other NRTI's? - ANSWER It only needs to be
phosphorylated twice, unlike the other because it *already has one phosphate* present
It *cannot be cleaved by cellular* esterases which increases its half-life
TDF vs TAF: dose needed - ANSWER TDF needs higher dose
TAF only needs low dose
TDF vs TAF: toxicities - ANSWER TDF: kidney toxicities due to higher plasma conc
TAF: lower plasma conc, no kidney toxicities
Why is tenofovir and emtracitabine recommended as initial combo tx? - ANSWER TFV
has long half-life
QD dosing
Decreased fat distribution
Diff resistant mutations covered
What should be tested before abacavir therapy and why? - ANSWER HLA-B*5701 should
be tested
(+) patients can have a fatal hypersensitivity rxn
,Resistance to NRTI's - ANSWER Discriminatory or excision
Discriminatory Mutation - ANSWER Selectively impair ability of reverse transcriptase to
incorporate NRTI's into DNA
Excision Mutation - ANSWER ATP mediates removal of NRTI from DNA after its been
incorporated
If there is resistance to one analog of NRTI, is it resistant to all? - ANSWER No
NRTI Tx Options *not* recommended - ANSWER Monotherapy (only zidovudine for
perinatal transmission prev)
2 NRTI's w/o another antiretroviral
3 NRTI's
1st gen NNRTI's vs 2nd gen - ANSWER 2nd gen are diaryl-pyrimidine based molecules
with *increased flexibility* that can bind multiple *mutants that are resistant* to other
NNRTI's
Fusion Inhibitors: MOA - ANSWER Binds *HIV gp41* to block confirmation change for
fusion
Fusion Inhibitors: Drugs - ANSWER Enfuvirtide
Fusion Inhibitors: Target - ANSWER HIV-1
Fusion Inhibitors: Resistance - ANSWER Mutations in the 10-AA chain can be *easily*
acquired
Entry Inhibitors: Drugs - ANSWER Maraviroc
Entry Inhibitors: MOA - ANSWER Binds *human CCR5* to block binding to gp120 for
entry
Entry Inhibitors: Target - ANSWER Only for *CCR5 HIV* patients
NRTI's: Drugs - ANSWER Zidovudine
Stavudine
Abacavir
Didanosine
Tenofovir
Zalcitabine
Lamivudine
,Emtricitabine
NRTI's: T analogs - ANSWER Zidovudine
Stavudine
NRTI's: G analogs - ANSWER Abacavir
NRTI's: A analogs - ANSWER Didanosine
Tenofovir
NRTI's: C analogs - ANSWER Lamivudine
Zalcitabine
Emtricitabine
NRTI's: MOA - ANSWER Integrates *into DNA* to *competively* inhibit reverse
transcriptase and inhibit elongation
NRTI's: Target - ANSWER HIV-1
HIV-2
NRTI's: Toxicities - ANSWER Mitochondrial
Lipoatrophy (decreased fat, highest w/ Stavudine)
NNRTI's: 1st Gen Drugs - ANSWER Nevirapine
Efaviren
Delaviridine
NNRTI's: 2nd Gen Drugs - ANSWER Etravirine
, Rilivirine
NNRTI's: MOA - ANSWER *non-competively* inhibit RT by binding a pocket *near* the
catalytic site —> affects enzymes shape —> no polymerization
NNRTI's: Toxicities - ANSWER Rash
Drug-drug interaction
Hepatotoxicity and Steven-Johnson's (nev.)
Neuropsychiatric and *teratogenic* (efav)
NNRTI's: Metabolism - ANSWER All metabolized by CYP3A4
NNRTI's: Resistanace - ANSWER Single mutation in binding site
Integrase Inhibitors: Drugs - ANSWER Raltegravir
Elvitegravir
Dolutegravir
Integrase Inhibitors: MOA - ANSWER Block *HIV DNA* being transferred into host cell
DNA
Integrase Inhibitors: CYP interactions - ANSWER (E) metabolized by CYP3A4
Replication cycle of HIV - ANSWER Attachment and fusion
Nucleocapsid released
Reverse transcription
Integration of DNA into nucleus
Viral RNA created
Budding and release
Protease cleaves to release HIV particles to other cells
How are NRTI's activated? - ANSWER All NRTI's are prodrugs that are activated after
being phosphorylation *3 times*
TDF vs TAF: cleavage - ANSWER TDF: plasma esterases
TAF: cellular esterases
How is Tenfovir different from other NRTI's? - ANSWER It only needs to be
phosphorylated twice, unlike the other because it *already has one phosphate* present
It *cannot be cleaved by cellular* esterases which increases its half-life
TDF vs TAF: dose needed - ANSWER TDF needs higher dose
TAF only needs low dose
TDF vs TAF: toxicities - ANSWER TDF: kidney toxicities due to higher plasma conc
TAF: lower plasma conc, no kidney toxicities
Why is tenofovir and emtracitabine recommended as initial combo tx? - ANSWER TFV
has long half-life
QD dosing
Decreased fat distribution
Diff resistant mutations covered
What should be tested before abacavir therapy and why? - ANSWER HLA-B*5701 should
be tested
(+) patients can have a fatal hypersensitivity rxn
,Resistance to NRTI's - ANSWER Discriminatory or excision
Discriminatory Mutation - ANSWER Selectively impair ability of reverse transcriptase to
incorporate NRTI's into DNA
Excision Mutation - ANSWER ATP mediates removal of NRTI from DNA after its been
incorporated
If there is resistance to one analog of NRTI, is it resistant to all? - ANSWER No
NRTI Tx Options *not* recommended - ANSWER Monotherapy (only zidovudine for
perinatal transmission prev)
2 NRTI's w/o another antiretroviral
3 NRTI's
1st gen NNRTI's vs 2nd gen - ANSWER 2nd gen are diaryl-pyrimidine based molecules
with *increased flexibility* that can bind multiple *mutants that are resistant* to other
NNRTI's
Fusion Inhibitors: MOA - ANSWER Binds *HIV gp41* to block confirmation change for
fusion
Fusion Inhibitors: Drugs - ANSWER Enfuvirtide
Fusion Inhibitors: Target - ANSWER HIV-1
Fusion Inhibitors: Resistance - ANSWER Mutations in the 10-AA chain can be *easily*
acquired
Entry Inhibitors: Drugs - ANSWER Maraviroc
Entry Inhibitors: MOA - ANSWER Binds *human CCR5* to block binding to gp120 for
entry
Entry Inhibitors: Target - ANSWER Only for *CCR5 HIV* patients
NRTI's: Drugs - ANSWER Zidovudine
Stavudine
Abacavir
Didanosine
Tenofovir
Zalcitabine
Lamivudine
,Emtricitabine
NRTI's: T analogs - ANSWER Zidovudine
Stavudine
NRTI's: G analogs - ANSWER Abacavir
NRTI's: A analogs - ANSWER Didanosine
Tenofovir
NRTI's: C analogs - ANSWER Lamivudine
Zalcitabine
Emtricitabine
NRTI's: MOA - ANSWER Integrates *into DNA* to *competively* inhibit reverse
transcriptase and inhibit elongation
NRTI's: Target - ANSWER HIV-1
HIV-2
NRTI's: Toxicities - ANSWER Mitochondrial
Lipoatrophy (decreased fat, highest w/ Stavudine)
NNRTI's: 1st Gen Drugs - ANSWER Nevirapine
Efaviren
Delaviridine
NNRTI's: 2nd Gen Drugs - ANSWER Etravirine
, Rilivirine
NNRTI's: MOA - ANSWER *non-competively* inhibit RT by binding a pocket *near* the
catalytic site —> affects enzymes shape —> no polymerization
NNRTI's: Toxicities - ANSWER Rash
Drug-drug interaction
Hepatotoxicity and Steven-Johnson's (nev.)
Neuropsychiatric and *teratogenic* (efav)
NNRTI's: Metabolism - ANSWER All metabolized by CYP3A4
NNRTI's: Resistanace - ANSWER Single mutation in binding site
Integrase Inhibitors: Drugs - ANSWER Raltegravir
Elvitegravir
Dolutegravir
Integrase Inhibitors: MOA - ANSWER Block *HIV DNA* being transferred into host cell
DNA
Integrase Inhibitors: CYP interactions - ANSWER (E) metabolized by CYP3A4
