Antiretrovirals Flashcards Preview

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Flashcards in Antiretrovirals Deck (44):
1

List two NRTIs

zidovudine, abacavir

2

List an NNRTI

efavirenz

3

List two protease inhibitors

ritonavir, atazanavir

4

List a membrane fusion inhibitor

enfuvirtide

5

List an entry inhibitor

maraviroc

6

List an integrase inhibitor

raltegravir

7

Fusion between HIV-1 envelope and the host cell membrane, mediated by viral surface ____ and ____ is essential for entry of HIV into the cell

gp120 and gp41

8

HIV must bind to CD4 as well as _____ in order to enter a cell

co-receptor, either CCR5 or CXCR4

9

Cleavage of HIV polyproteins by _____ is essential for mature virus formation

protease

10

Enfuvirtide is a peptide that was developed to inhibit a specific region of _____ ap

gp41

11

Enfuvitide is typically considered _________, meaning it is given to treatment experienced patients who have developed extensive resistance to other agents

salvage therapy

12

Describe how resistance to enfuvirtide can arise

Mutation in gp41 envelope gene

13

Describe the normal function of gp41

Envelope protein; two regions fold upon each other to form a six helix bundle that brings the virus closer to the host cell and is required for membrane fusion

14

What is the major adverse effect of enfuvirtide?

Must be injected 2x daily, leads to injection site reactions

15

Describe the mechanism of action of maraviroc

Inhibits attachment of viral gp120 to the CCR5 co-receptor on host cells

16

Describe appropriate use of maraviroc

Approved for treatment experienced patients with R5 tropic virus
Will not be effective in patients with X4 or mixed tropism

17

How does resistance to maraviroc arise?

Possible to have mutations in gp120 but more likely to have emergence of mixed tropic or X4 tropic virus

18

What is unique about maraviroc compared to all other HAART drugs?

Something from the host is inhibited instead of something from the virus

19

List the constituents of common combination drugs:
Combivir
Trizivir
Epzicom
Truvada

Combivir= Lamivudine + Zidovudine
Trizivir= Lamivudine + Zidovudine + Abacavir
Epzicom= Abacavir + Lamivudine
Truvada= Tenofovir + Emtricitabine

20

NRTIs are _____ analogues that lack ____ on the ribose sugar, so when they are incorporated by reverse transcriptase they cause termination of chain elongation

nucleoside analogues
3'OH

21

For NRTIs to become active, they must be _______ by host enzymes

phosphorylated

22

List three main functions of reverse transcriptase

- synthesizes the - strand of DNA with the viral RNA genome as the template
- hydrolyzes viral + RNA
- synthesizes the + strand of DNA

23

List a negative drug interaction that occurs between zidovudine and stavudine

Because thymidine kinase (TK) has a higher affinity for zidovudine than stavudine, zidovudine antagonizes the effects of stavudine.

24

Describe two main mechanisms of NRTI drug resistance

- mutations in RT allow the enzyme to discriminate between NRTIs and dTNPs
- mutations in RT that promote the hydrolytic removal of chain termination NRTIs to allow for continued DNA synthesis

25

True or false: significant cross resistance exists for NRTI drugs

True

26

What is one common, class wide adverse effect seen with NRTIs

Mitochondrial toxicity and lactic acidosis, hepatic steatosis

27

Describe the mechanism of mitochondrial toxicity caused by NRTIs

inhibition of DNA polymerase gamma
leads to a depletion of certain key mitochondrial proteins essential for the electron transport chain leading to a buildup of lactic acid and triglycerides.

28

What specific toxicity is associated with zidovudine?

bone marrow suppression

29

What specific toxicity is associated with didanosine?

pancreatitis, peripheral neuropathy

30

What specific toxicity is associated with stavudine?

peripheral neuropathy

31

What specific toxicity is associated with abacavir?

abacavir hypersensitivity syndrome

32

Describe abacavir hypersensitivity syndrome

fever, rash, headache, nausea, abdominal pain, cough and shortness of breath
abacavir gets linked onto a protein (ex EtOH dehydrogenase) in APCs, peptide with abacavir on it is bound by HLA-B5701. When this interaction occurs, there is activation of T cells and upregulation of interferon

33

NNRTIs block reverse transcriptase by binding an _________ site on the RT enzyme, inducing a conformational change.

allosteric site

34

True or false: Like NRTIs, NNRTIs must be phosphorylized in vivo in order to be active

False

35

Describe how resistance to NNRTIs can emerge

Mutation in NNRTI binding site, leads to high level resistance against first generation NNRTIs but can usually still use second generation agents
Resistance arises very quickly if NNRTIs are used as monotherapy

36

Describe the positive drug interaction that occurs between NNRTIs and NRTIs

some point mutations in RT that confer resistance to NNRTIs may sensitize RT to NRTIs by inhibiting phosphorolysis

37

What class-wide toxicities are seen with NNRTIs?

Rash and hepatotoxicity

38

What specific toxicity is associated with efavirenz?

CNS effects and teratogenicity

39

Describe the mechanism of raltegravir

Integrase inhibitor, docks in the acceptor DNA binding site and interferes with strand transfer

40

Describe the mechanism of action of protease inhibitors

Bind to active site o protease and prevent cleavage of gag-pol and blocks viral maturation

41

Why are lopinavir and ritonavir always formulated together?

A small dose of ritonavir is used in Kaletra to inhibit Cytochrome P450 CYP3A4 metabolism of Lopinavir and make it a viable drug

42

Describe class wide toxicity seen with protease inhibitors

Hepatotoxicity, GI upset, lipodystrophy, insulin resistance highly associated with protease inhibitors

43

What specific adverse reactions are seen with atazanavir?

hyperbilirubinemia and QT prolongation

44

Describe the difference between genotypic and phenotypic testing for drug resistance

Phenotypic: rate of growth of sample virus compared to wild virus in the presence of drug

Genotypic: sequence of sample compared to wild type virus