Pharm agents for HIV AIDS, Martin, DSA Flashcards
What are the Nucleoside/nNt Reverse transcriptase inhibitors
Emtricitabine
Tenofovir DF
Lamivudine
Zidovudine
What are the non-nucleoside reverse transcriptase inhibitors
Efavirenz
What are the protease inhibitors
Atazanavir
Darunavir
Lopinavir
Ritonavir
What are the Integrase Strand Transfer Inhibitors
raltegravir
What are the CCR5 Anatgonist/entry inhibitor
maraviroc
What are the fusion inhibitors
enfuvirtide
What is the preferred regimen to Tx drug-naive patients
backbone: 2 NNRTIs
base: one of these:
-NNRTI
Protease inhibitor
INSTI
CCR5 antagonist
What are the antiretroviral agent combinations
Emtircitabine +Tenofovir
DF
efavirenz+ emtricitabine+tenofovir DF
What are the drug regimens used during pregnangy
zidovudine + iopinavir + ritonavir Intrapartum period (IV) zidovudine
Infants from HIV mothers receive what drug and for how long
zidovudine for 6 mo
What are the pre and post exposure prophylaxis regimen for HIV
ralegravir + emtircitabine + tenofovir DF
goals of HIV therapy
reduce HIV assoc morbidity and prolong duration and quality of survival
rstore and preserve immunologic function
maximally and durably suppress plasma HIV viral load
prevent HIV transmission
why are combination druge regimens used
minimize development of resistance
What is CD4 count indicative of AIDS
<350
HIV Tx should be initiated regardless of CD4 in what patients
pregnant women
patients with HIV assoc nephropathy
patients co infected with hep B virus
CD4 T cell counts are used for what
decide when to initiate therapy
monitor the Therapeutic response
monitored every 3-4 mo
what is most important indicator of response to antiretroviral therapy
plasma HIV RNA (viral load)
What is considered a success in antiviral Tx HIV
decrease in viral load of 3X or more
viral suppression takes how long from initiation of Tx
12-24 mo
when is drug resistance testing recommended
patient enters care
there is a drug treatment failure
changing drug protocols
what is genotypic assays
involve sequencing of the reverse trasncriptase and protease genes to detect mutations that are known to confer drug resistance
What is recommended for pregnant women prior to initiation of Tx
genotypic resistance
phenotypic assays do what
measure ability of a virus to grow in a different [ ] of antiretroviral drugs
what are used to make pseudotyped viruses that express the patient-derived HIV genes of interest
when gene sequences are from patient plasma HIV RNA are inserted into the backbone of a laboratory clone of HIV
do NRTI and NNRTI bind to same sites
no 2 different sites
What is the preferred NNRTI? exception?
efavirenz
not in pregnant women or women who could be potentially pregnant in future
What is the preferred dual-NRTI
tenofovir/emtricitabine
Patient has HLA B5701, should not use what dual NRTI regimen
abacavir/lamivudine
have HS reaction
how does tenofovir inhibit reverse transcriptase
incorporated into growing viral DNa chain and causes chain termination
Tenofovir DF is avaiable in combination with what drugs
emtricitabine
emtricitabine and efavirenz
What is the best tolerated NRTI
emtricitabine
adverse effects emtricitabin
hyperpigmentation of palms and soles
emtricitabine is used to Tx what other condition besides HIV
HBV
side effects of zidovudine
anemia, neutropenia, nausea, vomiting, HA, fatigue, confusion, malaise, myopathy, hepatitis, hyperpigmentation or oral mucosa and nail beds
lipoatrophy, lactic acidosis and hepatic steatosis
how do the NNRTIs work
bind directly to reverse trancriptase blocking RNA and DNA-dependent DNA polymerase activity
what are the NNRTI drugs
efavirenz and delavirdine, necirapine, etravirine
when does R to efavirenz occur
when used as monoTx
only used in combinations to prevent this
NNRTI toxicity signs
CNS: dizzy, drowsy, insomnia, HA, confusion, agitation, depression
Psych: severe
Rash and HS syndrome, steven-johnson syndrome
What are the preferred protease inhibitor regimens
atazanavir + ritonavir
darunavir + ritonavir once daily
What is the alternative PI regimen
iopinavir + ritonavir
What 2NRTIs are give with PI
tenofovir/emtricitabine
how do protease inhibitors affect CYP3A4
inhibitors of it
why is low dose ritonavir given with other PIs
increases serum [ ]
PIs work how
prevent mature proteins, result in immature noninfective viral particles
result of monoTx of PI
contraindicated because cause phenotypic resistance
Adverse effects of PI
GI distress, increased bleeding in hemophliacs, hyperglycemia, insulin R and hyperlipidemia
assoc with increased risk of coronary artery disease
adverse effects of atazanavir (PI)
hyperbilirubinemia
rash in 20% that is mild or moderate
What is the role of HIV-1 integrase
catalyzes viral DNA insertion in host genome
what is the integrase inhibitor drug
raltegravir
What are the 2 major coR used by HIV-1 to gain entry
CCR5 and CXCR4
Maraviroc antagonizes what R
CCR5
how do you determine if HIV patient has R5 or X4
commercial assay
side effects maraviroc
cough, pyrexia, upper respiratory tract infection, rash, MSK Sx, abdominal pain and postural dizziness
if considering use of maraviroc what should be done
Coreceptor tropism assay
also done if virologic failure of drug is apparent
patient has CD4 <100
most likely R type
either X4 or dual or mixed-tropic because more resistant to Tx
MOA enfuvirtide
inhibition of fusion binding to gp41 of viral envelop glycoprotein & prevents conformational changes required for fusion of viral and cellular membranes
Administration of enfuvirtide
BID subcu
usually Tx-experienced patients
