HIV pharmacology/med chem

Question 1

HIV has what kind of nucleic acid structure

Answer 1

ssRNS with reverse transcriptase

Question 2

CD4 role in HIV life cycle

Answer 2

CD4 is on surface of T cells/macrophage and the HIV virion attaches to CD4, allowing entrance into the cell

Question 3

sequence of events in HIV life cycle

Answer 3

1. fusion of HIV to host cell
2. RNA, RT, integrase, and proteins enter
3. viral DNA is formed by RT
4. DNA is integrated with host DNA
5. new viral RNA is made, and viral proteins come as result
6. viral RNA and proteins moves to surface
7. virus is released and protease makes mature proteins

Question 4

classes of HIV drugs

Answer 4

• NRTIs
• NNRTIs
• protease inhibitors
• integrase inhibitors
• entry inhibitors

Question 5

NRTIs MoA

Answer 5

replace DNA/RNa components, but lack 3’ OH so they terminate the elongation chain

Question 6

NRTI resistance

Answer 6

associated with mutations in pol gene that encodes for RT

Question 7

NRTI adverse effects

Answer 7

mitochondrial toxicity leading to:

• neuropathy
• myopathy
• hepatic steatosis with lactic acidosis

Question 8

NRTI drugs

Answer 8

zidovudine*not as important*
lamivudine
abacavir
tenofovir
emtricitabine

Question 9

zidovudine features

Answer 9

very short half life so dosing is 2-6 times per day

Question 10

lamivudine features

Answer 10

• once daily dosing
• can reverse zidovudine resistance
• renal dosing is very important

Question 11

emtricitabine features

Answer 11

more potent than lamivudine with less severe side effects

Question 12

tenofovir features

Answer 12

• nucleoTIDE analog, not nucleoside
• prodrug
• poor outcomes when combined with other drugs

Question 13

NNRTI MoA

Answer 13

inhibit RT allosterically by binding noncompetitively at a distinct site from NRTIs

Question 14

notable ADME for NNRTI

Answer 14

all are metabolized by p450s so they are prone to drug interactions

Question 15

NNRTI resistance

Answer 15

RT mutations

Question 16

NNRTI side effects

Answer 16

severe rash

CNS symptoms

Question 17

NNRTI drugs

Answer 17

efavirenz
etravirine
rilpivirine

Question 18

efavirenz features

Answer 18

don’t use with GERD drugs

Question 19

etravirine features

Answer 19

• no cross resistance with other NNRTIs

- pregnancy class B

Question 20

rilpivirine features

Answer 20

-pregnancy class B

Question 21

protease inhibitors MoA

Answer 21

inhibit the protease that matures viral proteins at the end of the life cycle

Question 22

protease inhibitors ADME

Answer 22

metabolized by 3A4

Question 23

protease inhibitors adverse effects

Answer 23

• GI intolerance

- lipodystrophy

Question 24

protease inhibitor drugs

Answer 24

ritonavir
atazanavir
darunavir

Question 25

ritonavir use

Answer 25

because it is the most potent 3A4 inhibitor it is used to keep other drugs going longer, and not so much for its antiviral activity

Question 26

drugs used as 3A4 inhibitors to increase half life of other drugs

Answer 26

ritonavir | cobicistat

Question 27

atazanavir features

Answer 27

good tolerability with once daily dosing

Question 28

darunavir features

Answer 28

1st line option due to its high antiviral activity

Question 29

integrase inhibitors MoA

Answer 29

prevents transfer of viral DNA into host DNA (specifically inhibits strand transfer)

Question 30

integrase inhibitor ADME

Answer 30

not 3A4 inhibitors

Question 31

integrase inhibitor adverse effects

Answer 31

``` insomnia fatigue headache altered cholesterol hypersensitivity reactions ```

Question 32

integrase inhibitor drugs

Answer 32

raltegravir | dolutegravir

Question 33

drug that can cause stevens johnsons

Answer 33

raltegravir

Question 34

entry inhibitor MoA

Answer 34

prevents viral entry by blocking gp120 attachment to CCR5

Question 35

entry inhibitor drug

Answer 35

maraviroc

Question 36

why is combo therapy most effective in HIV

Answer 36

HIV has a very high mutation rate

Question 37

what modification is needed to make NRTIs active

Answer 37

phosphorylation (3 phosphates needed)

Question 38

when using multiple NRTIs what consideration must be made when choosing

Answer 38

the bases they mimic, double dipping doesn't add any benefit