HIV Pharm Flashcards
(48 cards)
1
Q
What does HIV bind to in order to enter cells?
A
CD4 and then either CXCR4 or CCR5
2
Q
Maraviroc MOA
A
- binds specifically to CCR5 to prevent viral entry into the host cell
- should test co-receptor tropism prior to initiating (if virus has tropism for CXCR4 then this drug will not work well)
3
Q
Maraviroc is used only in
A
those infected with virus with tropism for CCR5
4
Q
Maraviroc adverse effects
A
- generally well tolerated
- systemic allergic rxn then hepatotoxicity has been reported
5
Q
Enfuvirtide MOA
A
- fusion inhibitor
- binds to gp41 preventing conformational and structural changes needed to allow fusion of viral envelope with host membrane
6
Q
How is enfuvirtide administered?
A
subQ injection
7
Q
enfuvirtide AE
A
- local injection site rxns
- insomnia, HA, dizziness, nausea
- hypersensitivity is rare
8
Q
How are nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) used in tx of pts with HIV?
A
- included in nearly all tx regimens when beginning antiretroviral therapy
- Mostly provide protection to susceptible cells because if viral DNA is already integrated it will not do anything for those cells
9
Q
MOA of NRTIs
A
- competitive inhibition of HIV reverse transcriptase
- incorporates into growing viral DNA chain
- leads to premature chain termination due to inhibition of binding with the incoming nucleotide
10
Q
List the nucleoSIDE reverse transcriptase inhibitors
A
abacavir didanosine lamivudine emtricitabine stavudine zidovudine
11
Q
List the nucleoTIDE reverse transcriptase inhibitors
A
tenofovir
12
Q
What is unique about abacavir?
A
- metabolized by alcohol dehydrogenase
- serum levels increase with concurrent ethanol ingestion
- guanosine
13
Q
AE of abacavir
A
- hypersensitivity (within 1st 6 wks of therapy)
- fever, fatigue, nausea, vomiting, diarrhea
- resp sym: dyspnea, cough
- skin rash (50%)
14
Q
AE of didanosine
A
- dose dependent pancreatitis (conditions or drugs that may cause pancreatitis are contraindicated)
- retinal changes with optic neuritis (mandated periodic retinal exams)
15
Q
What is unique about lamivudine
A
- active against both HIV and HBV
- cytosine analog
- AE are uncommon (HA, dizziness, insomnia, fatigue)
16
Q
What is unique about emtricitabine
A
- active against HIV & HBV (so I guess it’s not unique idk)
- long half-life (once daily dosing)
17
Q
AE of emtricitabine
A
- HA, diarrhea, nausea, rash
- hyperpigmentation of palms & soles, esp in african americans
18
Q
AE of stavudine
A
- dose dependent peripheral sensory neuropathy
- dyslipidemia
19
Q
Which was the first antiretroviral drug to be approved?
A
zidovudine
20
Q
AE of zidovudine
A
- macrocytic anemia
- neutropenia
- GI intolerance, HA, insomnia
21
Q
which 3 NRTIs are active against HIV and HBV
A
lamivudine(side), emtricitabine(side), tenofovir (nucleotide)
22
Q
AE of tenofovir (only nucleotide reverse transcriptase inhibitor)
A
- generally well tolerated
- flatulence
23
Q
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) MOA
A
- binds directly to HIV reverse transcriptase in site distant from active site
- binding induces conformation change
24
Q
NNRTIs resistance
A
- develops rapidly with monotherapy
- HIV transcriptase point mutations that alter binding
- no cross resistance between NNRTIs and the NRTIs
25
AE of NNRTIs
-GI intolerance, skin rash
Metabolized by CYP450
26
First generation of NNRTIs
delavirdine
efavirenz
nevirapine
27
Second generation of NNRTIs
etravirine
| rilpivirine
28
What is the difference between 1st and 2nd gen NNRTIs
2nd gen are most potent, have longer 1/2 lives, and decreased side effects
29
AE of delavirdine
- skin rash
| - HA, fatigue, nausea, diarrhea
30
AE of efavirenz
- CNS (50%): dizziness, drowsiness, insomnia, nightmares
| - skin rash
31
What is unique about nevirapine
- first NNRTI to be approved for HIV
| - used in preventing transmission of HIV from mother to child
32
AE of nevirapine
- rash
| - liver toxicity
33
AE of etravirine
rash, nausea, diarrhea
34
AE of rilpivirine
- rash, depressiom HA, insomnia, increased serum aminotransferases
- high doses asssoc. with QT prolongation
35
MOA of integrase strand transfer inhibitors (INSTIs)
- binds HIV integrase
| - inhibits strand transfer & prevents ligation of reverse-transcribed HIV DNA int the chromosome of host cell
36
AE of INSTIs
well tolerated, HA & GI effects more common
37
List of INSTIs
all drugs end in "-gravir"
dolutegravir
elvitegravir
raltegravir
38
What does elvitegravir need to be combined with
cobicistat as a booster
39
Which drugs are preferred for tx naive pts?
- dolutegravir in combo with others
| - raltegravir
40
MOA of protease inhibitors
- block the HIV protease and prevent the maturation of the final structural proteins that make up the mature virion core
- specifically inhibits the action of HIV aspartyl protease
41
Protease inhibitors: resistance & AE
-resistance develops quickly with monotherapy
AE:
-GI intolerance
-hyperglycemia, hyperlipidemia, lipoatrophy, fat deposition
-redistribution & accumulation of fat
42
Protease inhibitors: metabolism
metabolized by CYP3A4
| -enormous potential for drug-drug interactions
43
List of protease inhibitors
```
atazanavir
darunavir
fosamprenavir
indinavir
lopinavir
nelfinavir
ritonavir
saquinavir
tipranavir
```
44
Darunavir must be co-administered with what?
ritonavir or cobicistat
45
AE of indinavir
unconjugated hyperbilirubinemia & nephrolithiasis
| --consumption of 48 ounces (1.5L) of water daily helps to prevent formation of kidney stones
46
Ritonavir is primarily used as?
a booster
- -very potent CYP450 inhibitor
- -high rate of GI SE at standard doses
47
When is tipranavir indicated?
in pts resistant to other protease inhibitors
| -combined with ritonavir
48
Highly active antiretroviral therapy (HAART)
2 NRTIs plus either:
- 1 protease inhibitor (sometimes 2 for boosting)
- 1NNRTI
- 1 INSTI
