Anti-retrovirals Flashcards
(87 cards)
1
Q
abacavir
A
NRTI
2
Q
didanosine
A
NRTI
3
Q
emtricitabine
A
NRTI
4
Q
lamivudine
A
NRTI
5
Q
stavudine
A
NRTI
6
Q
tenofovir
A
NRTI
7
Q
zidovudine
A
NRTI
8
Q
efavirenz
A
NNRTI
9
Q
nevirapine
A
NNRTI
10
Q
rilpivirine
A
NNRTI
11
Q
atazanavir
A
protease inhib
12
Q
darunavir
A
protease inhib
13
Q
indinavir
A
protease inhib
14
Q
lopinavir
A
protease inhib
15
Q
nelfinavir
A
protease inhib
16
Q
enfuviritide
A
entry inhibitor
17
Q
maraviroc
A
entry inhibitor
18
Q
dolutegravir
A
integrase inhib
19
Q
elvitegravir
A
integrase inhib
20
Q
raltegravir
A
integrase inhib
21
Q
cobicistat
A
pharmacokinetic enhancers
22
Q
ritonavir
A
pharmacokinetic enhancer
23
Q
NRTI MOA
A
riboside analog - lacking 3’ OH
phosphorylated by cell enzymes, incorp into viral DNA = terminates DNA elongation
COMPETITIVE INHIB of RT
active against HIV-1 and 2
(1 - western world. 2 - west africa)
24
Q
NRTI resistance
A
rapidly emerges if used alone
most common mutation at viral codon 184 - lamivudine; can inc sensitivity to zidovudine and tenofovoir
cross resistance does occur
dose changes with renal insufficiency
25
NRTI AE
inhib mitochondrial DNA pol = periph neuropathy, myopathy, lipoatrophy, lactic acidosis
pancreatitis
myelosuppression
fatal liver toxicity - rare
zidovudine and stavudine = dyslipidemia, insulin resistance
26
NRTI interactions
didanosine and tenofovir: tenofovir inc didanosine levels (must reduce didanosine levels)
not metabolized by cytochrome enzymes
27
zidovudine
thymidine analog
(ZDV, AZT)
oral
crosses BBB
dosage adj in cirrhosis
28
zidovudine AE
BM suppression
29
ganciclovir + zidovudine
BOTH CAUSE BM SUPPRESSION - don't give together
30
zidovudine contraindications
coadmin with acetaminophen, lorazepam, indomethacin, cimetidine
31
Stavudine
(d4T)
inhibitor of beta and gamma DNA polymerases (high aff for mitochondrial DNA pol)
thymidine analog
oral
32
stavudine AE
peripheral neuropathy
lactic acidosis
hyperlipidemia
NM weakness
33
Didanosine
adenosine analog
best if taken in fasting state - acid labile
penetrates CSF
34
Didanosine AE
PANCREATITIS
peripheral neuropathy, diarrhea, hepatic dysfunction, CNS effects
35
Tenofovoir
(TDF)
adenosine nucleotide analog
combos: tenofovir + emtricitabine AND tenofovir + emtricitabine + efavirenz
36
tenofovir PK
take with food to inc bioavail
long t 1/2
37
only NRTI with significant drug interaction
tenofovir + didanosine
Tenofovir decreases concentrations of atazanavir
Can boost atazanavir with ritonavir
38
Lamivudine
(3TC)
no affect on mitochondrial DNA or BM
cytosine nucleoside analog
39
emtricitabine
relative of lamivudine
cytosine nucleoside analg
40
emtricitabine AE
hyperpigmentation - more frequently in darker skinned
41
abacavir
guanosine nucleoside analog
42
abacavir AE
GI, HA
5% hypersensitivity reaction - rash, GI, malaise, respiratory distress
CONTRAINDIC in HLA-B 5701 mutation
don't ever rechallenge sensitized individuals
43
NNRTI MOA
selectively, noncomp inhibitor of HIV-1 RT
don't bind at active site
inhibit RNA and DNA dep DNA pol
NO phosphorylation by cellular enzymes
no activity against HIV-2
44
NNRTI adv/disadv
no cross resistance, effect on host blood forming elements
cross ressistance within NNRTI's. drug interactions. high incidence of hypersensitivty
45
NNRTI's AE
skin rash -- stevens johnson syndrome
CYP3A4 substrates: can act as inducers, inhibitors, or both of CYP
46
Nevirapine excretion
urine - CYP3A4, 2B6
47
nevirapine AE
hepatotoxicity (severe)
- don't use unless have to
rash
titration period for 14 days at 1/2 dose to dec risk of serious epidermal reactions
48
nevirapine PK
CYP3A4 inducer
increases metab of PI's , OCP, ketoconazole, methoadone, metronidazole, quinidne, theophylline, warfarin
49
efavirenz
increases CD4+ counts, dec viral load
oral
40 hr half life
P450 inducer
50
efavirenz AE
high rate of CNS toxicity
rash
inc TG, HDL, cholest (must monitor lipids)
contraindcated in pregnancy - but can be used after 1st trimerster
51
Rilpivirine AE
**Rash
insomina, depression
LFTs increased
52
Protease inhibitor MOA
reversible inhib of HIV aspartyl protease = prevents viral maturation and production of non-infectious virions
NO intracellualr activ required
active against HIV-1 and 2
53
Protease inhib PK
poor oral bioavail -
high fat inc = nelfinavir
high fat dec = indinavir
substrate for CYP3A4
substrate for P glycoprotein pump
bound to plasma proteins = dec amt of free drug available to pt (alpha1-acid glycoprotein)
54
protease inhib AE
parathesias, n/v/d
disturbances in lipid metab
fat redistribution and accum: central obesity, dorsocervical fat enlargement - buffalo hump, peripheral wasting; cushingoid appearance --> AE decreases compliance
55
protease inhib contraindic
CYP inhibitors
- rhabdo (simvastain), excess sedation (midzolam), respiratory depression (fentanyl)
warfarin, sildenafil, phenytoin - require dosage adj
contraindic with rifampin and st john's wort
56
PI resistance
stepwise mutations of protease gene
57
atazanavir AE
PR interval prolongation
benign hyperbilirubinemia
rash
nephrolithiasis
58
Which protease inhib is NOT given with RTV
Nelfinavir
b/c metabolized by several CYPs
59
Enfuviritide
(T-20)
inhibits viral fusion
"Tx-experienced pt with evidence of HIV replication"
No activity against HIV-2
60
enfuviratide MOA
gp41 structural analog
| binds gp41 - prevent ability of virion to fuse to cell membrane
61
enfuvirataide contraindications
NO drug interactions with other retrovirals
62
Maraviroc MOA
binds only CCR5 - blocking HIV entry
63
maraviroc PK
CYP3A4 metabolized
64
Integrase strand transfer inhibitor
approved for tx experienced and tx naive
65
INSTI MOA
binds integrase
| inhibits final step of integration of viral DNA into host cell DNA
66
INSTI's AE
rash, nausea, diarrhea, insomnia, HA
inc in creatine phosphokinases, myopathy, rhabdo, hypersensitivity
67
Dolutegravir
eliminated via glucronidation via UGT1A1
68
Elvitegravir
CYP3A4 metabolized - may require enhancer (Cobicistat)
69
Raltegravir
eliminiated by glucoronidation by UGT1A1
70
raltegravir AE
can cause increases in creatine phosphokinases
71
raltegravir interactions
rifampin
tipranavir
efavirenz
= may dec raltegravir
PPI can increase raltegravir
72
ritonavir
PK enhancer
73
cobicistat
PK enhancer
74
PK enhancer MOA
CYP3A4 inhibitor
Inc plasma concen of ARV = allows for lower and/or less frequent dosing
improves tolerability of ARV
75
Ritonavir use
in combo with PI's (not nelfinavir)
NEVER USED ALONE
76
what drug is ritonavir never used with?
nelfinavir
77
cobicistat use
combo with INSTI - elvitegravir, also with darunavir and atazanavir
78
Initial Tx for Treatment-naive pt
2x NRTI + INSTI
OR
2x NRTI + PI
avoid use of 2 agents of same nucleotide analog, overlapping toxicity
79
INSTI based regiments
1) Raltegravir + tenofovir + emtricitabine
| 2) Dolutegravir + tenofovir + emtricitabine
80
PI based regiment
Ritonavir boosted with darunavir + tenofovir + emtricitabine
81
HIV prophylaxis following needle stick
raltegravir + tenofovir + emtricitabine (x28 days)
82
HIV prophylactic vaccines
S. pneumo
HAV
HBV
Influenza
83
Vaccines contraindic in HIV pt with CD4 <200
LIVE VACCINES:
MMR
Varicella
Zoster
84
darunavir
inhibits CYP3A4
avoid in pt with sulfur allergy
85
indinavir
give with RTV
absorption dec with meals
nephrolithiasis
hyperbili
blurred vision
86
lopinavir
give with RTV
contraindic with inducers (St. Johns wort)
Avoid with disulfiram or metronidazole - contains EtOH
87
nelfinavir
lots of contraindications b/c CYP inhibition
