Anti-retrovirals Flashcards Preview

PHARM 2 > Anti-retrovirals > Flashcards

Flashcards in Anti-retrovirals Deck (87):
1

abacavir

NRTI

2

didanosine

NRTI

3

emtricitabine

NRTI

4

lamivudine

NRTI

5

stavudine

NRTI

6

tenofovir

NRTI

7

zidovudine

NRTI

8

efavirenz

NNRTI

9

nevirapine

NNRTI

10

rilpivirine

NNRTI

11

atazanavir

protease inhib

12

darunavir

protease inhib

13

indinavir

protease inhib

14

lopinavir

protease inhib

15

nelfinavir

protease inhib

16

enfuviritide

entry inhibitor

17

maraviroc

entry inhibitor

18

dolutegravir

integrase inhib

19

elvitegravir

integrase inhib

20

raltegravir

integrase inhib

21

cobicistat

pharmacokinetic enhancers

22

ritonavir

pharmacokinetic enhancer

23

NRTI MOA

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

NRTI resistance

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