C.6. Antiretroviral agents

Question 1

what do NRTI’s stand for?

Answer 1

Nucleoside/Nucleotide reverse transcriptase inhibitors

Question 2

what is the mechanism of action of NRTI’s?

Answer 2

competitively inhibit the binding of natural nucleotides to reverse transcriptase (RNA- dependent DNA polymerase enzyme)
act as a DNA chain terminator, binding with no 3’ OH group

Question 3

What are NRTI’s?

Answer 3

prodrugs, converted by host cell kinases to triphosphates

Question 4

when does Resistance happen when giving NRTI’s or NNRTI’s?

Answer 4

when using a single agent, via mutations in the Pol Gene

Question 5

side effects of NRTI’s

Answer 5

GI distress 
headache, fatigue 
hepatotoxicity 
lactic acidosis 
mitochondrial toxicity

Question 6

list the NRTI’S

Answer 6

Abacavir (ABC)
Emtricitabine (FTC)
Lamivudine (3TC)
Zidovudine (ZDV)
*have you dined (vudine) with my nuclear (nucleosides) family 
Tenofovir (TDF)

Question 7

which NRTI is a nucleotide?

Answer 7

Tenofovir

all the others are nucleosides, require more phosphorylation steps for activation

Question 8

which NRTI’s are used for hepatitis B infection?

Answer 8

Lamivudine

Tenofovir

Question 9

which NRTI’s is a Guanosine analogue?

Answer 9

Abacavir

Question 10

which NRTI is used during pregnancy and lactation?

Answer 10

Zidovudine

Question 11

what are the contraindications for giving Emtricitabine?

Answer 11

pregnancy, children, renal or hepatic dysfunction

Question 12

which NRTI is the least potent and least toxic agent?

Answer 12

Lamivudine

Question 13

which NRTI is the most toxic?

Answer 13

zidovudine

bone marrow suppression–> may need blood transfusions

Question 14

which metabolism does Zidovudine have?

Answer 14

hepatic+ renal elimination

Question 15

which NRTI is a more potent agent of Lamivudine?

Answer 15

Emtricitabine

Question 16

which type of toxicity does Tenofovir cause?

Answer 16

Nephrotoxicity

Question 17

what are the SE’s of Abacavir treatment?

Answer 17

allergy

associated with HLA-B *57:01 allele

Question 18

what is the SE of Emtricitabine?

Answer 18

GI distress

Question 19

what does Lamivudine cause?

Answer 19

peripheral neuropathy (mild)

Question 20

what are NNRTI’s

Answer 20

Non- nucleoside reverse transcriptase inhibitors

Question 21

NNRTI’s are not active against..?

Answer 21

HIV-2 strains

Question 22

what is the mechanism of NNRTI’s?

Answer 22

bind to a site on reverse transcriptase different from the binding site of NRTI’s

Question 23

a synergistic effect is achieved when NNRTI’s is used with..

Answer 23

NRTI’s and/or PI’s

Question 24

is there cross-resistance of NNRTI’s with NRTI’s?

Answer 24

no

Question 25

what is Etravirine?

Answer 25

the newest NNRTI approved for HIV treatment (2nd gen') | maybe effective against strains resistant to other NNRTI's

Question 26

side effects of Etravirine

Answer 26

rash, nausea, diarrhea

Question 27

is Etravirine an inducer or inhibitor of CYP450 enzymes

Answer 27

both | extensive drug-drug interactions

Question 28

what is Elvitegravir?

Answer 28

Integrase inhibitor

Question 29

what is the mechanism of action of Elvitegravir (tegra)

Answer 29

pyrimidine derivative that binds integrase | inhibits the integration of transcribed viral DNA into host cell chromosomes

Question 30

is Elvitegravir safe during pregnancy?

Answer 30

yes

Question 31

how do we give Elvitegravir?

Answer 31

orally

Question 32

what are the SE of Elvitegravir

Answer 32

↑ CK, myopathy, rhabdomyolysis | nausea, headache, dizziness

Question 33

list the protease inhibitors

Answer 33

Ritonavir Darunavir Lopinavir "Navir (Never) tease a protease"

Question 34

which proton inhibitor is the most commonly used?

Answer 34

Ritonavir

Question 35

which PI is used in combination with Ritonavir in patients resistant to other PI's?

Answer 35

Darunavir

Question 36

mechanism of action of Protease inhibitors

Answer 36

inhibits Aspartate protease (encoded by Pol gene)

Question 37

what is the mechanism of resistance of PI's?

Answer 37

specific point mutations in the Pol gene

Question 38

are all the PI's substrates and inhibitors of cytochrome P450 enzymes?

Answer 38

yes, | extensive drug-drug interactions

Question 39

the fact the PI's inhibits lipid-regulating proteins has led to the development of..

Answer 39

metabolic disorder

Question 40

which PI is used in combination with subtherapeutic dose of Ritonavir?

Answer 40

Lopinavir ritonavir inhibits lopinavir metabolism --> enhances it's activity

Question 41

which PI is the most potent inhibitor of P450 enzymes?

Answer 41

ritonavir | boost other drug concentrations

Question 42

what are the SE of ritonavir

Answer 42

Gi distress, bitter taste | hepatotoxicity

Question 43

what are the SE of Darunavir

Answer 43

GI distress, skin rash | sulfonamide hypersensitivity reaction

Question 44

what is Maraviroc?

Answer 44

CCR5 receptor inhibitor --> prevent interaction between viral gp120 and CD4 on the target cell

Question 45

is Maraviroc given with other antiretroviral agents?

Answer 45

yes

Question 46

how is Maraviroc given?

Answer 46

oral

Question 47

what are the SE of Maraviroc

Answer 47

cough diarrhea muscle and joint pain ↑ liver enzymes

Question 48

what is the approach for HAART? give examples

Answer 48

initiation of 3 antiretroviral drugs ('2+1 role'), before symptoms appear (if possible) Tenofovir+Emtricatbine+ Etravirine (NNRTI) Tenofovir+Emtricatbine+ Ritonavir (PO) Tenofovir+Emtricatbine+ Elvitegravir (Integrase inhibitor)

Question 49

what is PrEP?

Answer 49

pre-exposure prophylaxis | Tenofovir +Emtricitabine

Question 50

what is PEP?

Answer 50

post-exposure prophylaxis | Tenofovir +Emtricitabine +/- Reltegravir

Question 51

what do we give for pregnancy antiretroviral prophylaxis?

Answer 51

2+1 regimen +zidovudine | prevent vertical transmission