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Flashcards in Sweatman antiretroviral therapy Deck (67):
1

Primary means by which we treat HIV

>antimetabolite inhibitors of viral RT and
> inibitors of viral aspartate protease
*3 or more drugs before symptoms appear=best outcome

2

Name the NRTI's

ABACAVIR
LAMIVUDINE (3-TC) TENOFOVIR DISOPROXIL
ZIDOVUDINE (AZT) EMTRICITABINE
didanosine (ddI)
stavudine (D4T)

3

NRTI's MOA

prodrugs that must be converted by HOST kinases to trinucleotides in the body-->competitively inhibit dNTP bind site and cause chain termination
*lack 3' hydroxyl group--next attachment is therefore impossible

4

resistance to NRTI's occurs thru

mutations in the pol gene

5

guanisine analog NRTI

abacavir
*slow resistance

6

NRTI contraindicated in pregnancy and young pt.'s, renal.heaptic dysfunction

Emtricitabine

7

common side effect of emtricitibine

asthenia, gi distress, hyperpigmentation of the palms

8

lamivudine excretion

excusively kidney
*adjust dose if kidney problems

9

lamivudine NRTI is also useful against

HBV

10

Nucleotide that acts as a NRTI

tenofovir

11

tenofovir aslo useful against..

HBV

12

oral F of tenofovir

25-40%
*half life is 60 hrs
*renal elimination

13

tenofovir contraindicated if...

concurrent acyclovir. ganciclovir tx.
fanconi's anemia

14

lamivudine aka

3-tc

15

zidovudine (zdv) formerly known as

azt

16

prototype NRTI

zidovudine

17

Distribution of ZDV

most tissues including CNS

18

elimination of ZDV

hepatic metabolism to glucuronides and renal excretion

19

DOsage reduction of ZDV indicated if

uremic pt.'s and those with cirrhosis

20

primary toxicity of ZDV

bone marrow supression--> leading to anemia and neutropenia possibly requiring transfusions

21

drugs that increase the concentration of ZDV

azoles, and protease inhibitors

22

drugs that decrease concentration of ZDV

rifampin increases clearance

23

NRTI's taken with other antiretroviral agents may cause

lactic acid acidemia and sever hepatomegaly with steatosis

24

Name the NNRTI's

Efavirenz
Nevirapine

25

used to prevent vertical transmission of HIV during childbirth

nevirapine an NNRTI

26

NNRTI MOA

bind to a site on RT that is NOT the active site--> p66 of RT causing a conformational change (inhibit it)

27

Do NNRTI's need to be converted

no--> they are administered in the active form (unlike NRTI's) do not reauire phosphrylation to comepete with Nucleotides

28

resistance to NNRTI's

mutations in the POL gene (occurs rapidly if used as monotherapy)

29

Efavirenz bioavailability can be increased via

take with fatty foods

30

Efavirenze metabolism

hepatic cyp450's--> many drug-drug interxns

31

toxicity of Efavirenze

CNS dysfuntion, Skin rash, hyperlipidemia

32

should efavrienze NNRTI be taken dureing pregnancy

NO--> especially in first trimester

33

Nevirapine bioavailability

good, penetrates most tissues including CNS

34

metabolism of nevirapine

hepatic CYP3a4

35

toxicity of nevirapine

rash (15-20%)
Stevens-Johnson syndrome--> toxic epidermal skin necrolysis

36

nevirapine blood levels increased by

cimetidine and macrolide ab's

37

plasma blood levels of nevirapine decreased by

rifampin (cyp 3a4 inducer)

38

name the aspartate protease inhibitors

ATAZANAVIR
RITONAVIR
amprenavir
indinavir
lopinavir
nelfinavir
saquinavir

39

How do protease inhibitors work

disallows HIV1 aspartate protease inhibitor from cleaving precursor polyproteins to form the final structural proteins of the mature virion core--> mature virions cannot be made and inhibitos viral load

40

assembly of mature vririons relies on

HIV-1 specific aspartate protease inhibitor encoded by POL gene-->

41

resistance to protease inh=

mutations in the POL gene

42

all PI's are substrates for

cyp3a4

43

PI with the most profound inhibitory effect on cyp3a4

ritonavir

44

oral absorption of azatanovir requires

acidic environment--> should avoid antacids by 12 hrs

45

elimniation of atazanavir

biliary

46

distribution of atazanavir

CSF and seminal fluid

47

High doses of atazanavir-

prolonged QT--> proarrhythmogenic

48

cyps inhibited by atazanavir

cyp3a4 and cyp2d6

49

elimination of ritonavir

hepatic--> dosage reduction if liver fialure

50

drugs that reduce conc. of ritonavir

anticonvulsants and rifampin

51

drugs that increase con. of ritonavir

azoles, cimetidine, erythromycin

52

ritonavir is a substrate for which cyp

CYP3a4

53

rationale for combo use to 2 PI's

subtherapeutic ritonavir will be metabolized by CYP3a4 and will inhibit it..therfore the other PI will have greater availability and a greater effect

54

CCR5 inibitor

maraviroc

55

name the fusion inhibitors

maraviroc
enfuvirtide

56

target of maraviroc

CCR5
*HUMAN PROTEIN TARGET--BIG DEAL!

57

CCR5 MAINLY ON

MACROPHAGES AND ALSO A LITTLE ON T CELLS
CXCR4 ONLY ON T CELLS--> THIS MUTATION ACCOUNTS FOR RAPID LOSS OF CD4 T CELL IN AIDS

58

MARAVIROC ELEIMINATION

CYP3A4--> DOSAGE ADJUSTMENT IF OTHER DRUGS TARGETING THIS SUCH AS PI'S
DISTRIBUTION IS GOOD

59

SIDE EFFECT OF MARAVIROC

INCREASE HEPATIC TRANSAMINASES-->LIVER DAMAGE

60

ENFUVIRTIDE MOA

binds gp41 and her2 subunit and disallows fusion stalk from undergoing needed conformational changes forming--> HIV cannot get into the cell

61

resistance to Enfuvirtide=

env gene

62

indication for enfuvirtide

in pt's with persistent HIV1 repliation in site of ongoing therapy

63

metabolism of anfuvirtide

hydrolysis and NOT metabolized by CYP's

64

HIV1 integrase inhibitor

raltegravir

65

will work on HIV1 and HIV2

raltegravir

66

used to treat HIV naive pt.'s

raltegravir-->usually in combo regimens

67

metabolism of raltegravir

glucuronidation and not CYP metabolism