HIV pharmacology/med chem Flashcards Preview

PT3 ID 1 (HIV) > HIV pharmacology/med chem > Flashcards

Flashcards in HIV pharmacology/med chem Deck (38):
1

HIV has what kind of nucleic acid structure

ssRNS with reverse transcriptase

2

CD4 role in HIV life cycle

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

3

sequence of events in HIV life cycle

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

4

classes of HIV drugs

-NRTIs
-NNRTIs
-protease inhibitors
-integrase inhibitors
-entry inhibitors

5

NRTIs MoA

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

6

NRTI resistance

associated with mutations in pol gene that encodes for RT

7

NRTI adverse effects

mitochondrial toxicity leading to:
-neuropathy
-myopathy
-hepatic steatosis with lactic acidosis

8

NRTI drugs

zidovudine*not as important*
lamivudine
abacavir
tenofovir
emtricitabine

9

zidovudine features

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

10

lamivudine features

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

11

emtricitabine features

more potent than lamivudine with less severe side effects

12

tenofovir features

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

13

NNRTI MoA

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

14

notable ADME for NNRTI

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

15

NNRTI resistance

RT mutations

16

NNRTI side effects

severe rash
CNS symptoms

17

NNRTI drugs

efavirenz
etravirine
rilpivirine

18

efavirenz features

don't use with GERD drugs

19

etravirine features

-no cross resistance with other NNRTIs
-pregnancy class B

20

rilpivirine features

-pregnancy class B

21

protease inhibitors MoA

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

22

protease inhibitors ADME

metabolized by 3A4

23

protease inhibitors adverse effects

-GI intolerance
-lipodystrophy

24

protease inhibitor drugs

ritonavir
atazanavir
darunavir

25

ritonavir use

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

26

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

ritonavir
cobicistat

27

atazanavir features

good tolerability with once daily dosing

28

darunavir features

1st line option due to its high antiviral activity

29

integrase inhibitors MoA

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

30

integrase inhibitor ADME

not 3A4 inhibitors

31

integrase inhibitor adverse effects

insomnia
fatigue
headache
altered cholesterol
hypersensitivity reactions

32

integrase inhibitor drugs

raltegravir
dolutegravir

33

drug that can cause stevens johnsons

raltegravir

34

entry inhibitor MoA

prevents viral entry by blocking gp120 attachment to CCR5

35

entry inhibitor drug

maraviroc

36

why is combo therapy most effective in HIV

HIV has a very high mutation rate

37

what modification is needed to make NRTIs active

phosphorylation (3 phosphates needed)

38

when using multiple NRTIs what consideration must be made when choosing

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