Sweatman antiretroviral therapy

Question 1

Primary means by which we treat HIV

Answer 1

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

Question 2

Name the NRTI’s

Answer 2

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

Question 3

NRTI’s MOA

Answer 3

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

Question 4

resistance to NRTI’s occurs thru

Answer 4

mutations in the pol gene

Question 5

guanisine analog NRTI

Answer 5

abacavir

*slow resistance

Question 6

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

Answer 6

Emtricitabine

Question 7

common side effect of emtricitibine

Answer 7

asthenia, gi distress, hyperpigmentation of the palms

Question 8

lamivudine excretion

Answer 8

excusively kidney

*adjust dose if kidney problems

Question 9

lamivudine NRTI is also useful against

Answer 9

HBV

Question 10

Nucleotide that acts as a NRTI

Answer 10

tenofovir

Question 11

tenofovir aslo useful against..

Answer 11

HBV

Question 12

oral F of tenofovir

Answer 12

25-40%

• half life is 60 hrs
• renal elimination

Question 13

tenofovir contraindicated if…

Answer 13

concurrent acyclovir. ganciclovir tx.

fanconi’s anemia

Question 14

lamivudine aka

Answer 14

3-tc

Question 15

zidovudine (zdv) formerly known as

Answer 15

azt

Question 16

prototype NRTI

Answer 16

zidovudine

Question 17

Distribution of ZDV

Answer 17

most tissues including CNS

Question 18

elimination of ZDV

Answer 18

hepatic metabolism to glucuronides and renal excretion

Question 19

DOsage reduction of ZDV indicated if

Answer 19

uremic pt.’s and those with cirrhosis

Question 20

primary toxicity of ZDV

Answer 20

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

Question 21

drugs that increase the concentration of ZDV

Answer 21

azoles, and protease inhibitors

Question 22

drugs that decrease concentration of ZDV

Answer 22

rifampin increases clearance

Question 23

NRTI’s taken with other antiretroviral agents may cause

Answer 23

lactic acid acidemia and sever hepatomegaly with steatosis

Question 24

Name the NNRTI’s

Answer 24

Efavirenz

Nevirapine

Question 25

used to prevent vertical transmission of HIV during childbirth

Answer 25

nevirapine an NNRTI

Question 26

NNRTI MOA

Answer 26

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

Question 27

Do NNRTI's need to be converted

Answer 27

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

Question 28

resistance to NNRTI's

Answer 28

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

Question 29

Efavirenz bioavailability can be increased via

Answer 29

take with fatty foods

Question 30

Efavirenze metabolism

Answer 30

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

Question 31

toxicity of Efavirenze

Answer 31

CNS dysfuntion, Skin rash, hyperlipidemia

Question 32

should efavrienze NNRTI be taken dureing pregnancy

Answer 32

NO--> especially in first trimester

Question 33

Nevirapine bioavailability

Answer 33

good, penetrates most tissues including CNS

Question 34

metabolism of nevirapine

Answer 34

hepatic CYP3a4

Question 35

toxicity of nevirapine

Answer 35

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

Question 36

nevirapine blood levels increased by

Answer 36

cimetidine and macrolide ab's

Question 37

plasma blood levels of nevirapine decreased by

Answer 37

rifampin (cyp 3a4 inducer)

Question 38

name the aspartate protease inhibitors

Answer 38

``` ATAZANAVIR RITONAVIR amprenavir indinavir lopinavir nelfinavir saquinavir ```

Question 39

How do protease inhibitors work

Answer 39

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

Question 40

assembly of mature vririons relies on

Answer 40

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

Question 41

resistance to protease inh=

Answer 41

mutations in the POL gene

Question 42

all PI's are substrates for

Answer 42

cyp3a4

Question 43

PI with the most profound inhibitory effect on cyp3a4

Answer 43

ritonavir

Question 44

oral absorption of azatanovir requires

Answer 44

acidic environment--> should avoid antacids by 12 hrs

Question 45

elimniation of atazanavir

Answer 45

biliary

Question 46

distribution of atazanavir

Answer 46

CSF and seminal fluid

Question 47

High doses of atazanavir-

Answer 47

prolonged QT--> proarrhythmogenic

Question 48

cyps inhibited by atazanavir

Answer 48

cyp3a4 and cyp2d6

Question 49

elimination of ritonavir

Answer 49

hepatic--> dosage reduction if liver fialure

Question 50

drugs that reduce conc. of ritonavir

Answer 50

anticonvulsants and rifampin

Question 51

drugs that increase con. of ritonavir

Answer 51

azoles, cimetidine, erythromycin

Question 52

ritonavir is a substrate for which cyp

Answer 52

CYP3a4

Question 53

rationale for combo use to 2 PI's

Answer 53

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

Question 54

CCR5 inibitor

Answer 54

maraviroc

Question 55

name the fusion inhibitors

Answer 55

maraviroc | enfuvirtide

Question 56

target of maraviroc

Answer 56

CCR5 | *HUMAN PROTEIN TARGET--BIG DEAL!

Question 57

CCR5 MAINLY ON

Answer 57

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

Question 58

MARAVIROC ELEIMINATION

Answer 58

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

Question 59

SIDE EFFECT OF MARAVIROC

Answer 59

INCREASE HEPATIC TRANSAMINASES-->LIVER DAMAGE

Question 60

ENFUVIRTIDE MOA

Answer 60

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

Question 61

resistance to Enfuvirtide=

Answer 61

env gene

Question 62

indication for enfuvirtide

Answer 62

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

Question 63

metabolism of anfuvirtide

Answer 63

hydrolysis and NOT metabolized by CYP's

Question 64

HIV1 integrase inhibitor

Answer 64

raltegravir

Question 65

will work on HIV1 and HIV2

Answer 65

raltegravir

Question 66

used to treat HIV naive pt.'s

Answer 66

raltegravir-->usually in combo regimens

Question 67

metabolism of raltegravir

Answer 67

glucuronidation and not CYP metabolism