HIV drugs Flashcards Preview

Heme Pharm > HIV drugs > Flashcards

Flashcards in HIV drugs Deck (54):
1

Fusion inhibitor: Enfuvirtide: 36 amino acid peptide which binds to 1) inhibiting 2) of HIV with the target cell

1) gp41 2)fusion

2

active against HBV, patients co-infected with HIV and HBV should be closely monitored if treatment with either of these drugs is interrupted or discontinued, because of the likelihood of hepatitis flare

NRTIs (Emtricitabine, Lamivudine, Tenofovir):

3

36 amino acid peptide which binds to gp41 inhibiting fusion of HIV with the target cell

Fusion inhibitor: Enfuvirtide

4

a/e Metabolic changes including increased lipids, insulin insensitivity, and central fat accumulation

Protease inhibitors: Atazanavir, Darunavir, Ritonavir

5

binds to CD4

gp120

6

Binds specifically and selectively to CCR5

Penetration blocker: Maraviroc

7

Penetration blocker: Maraviroc resistance

develop due to mutations in gp120

8

Adverse effects i. Rash which could progress to Stevens-Johnson syndrome ii. Fetal abnormalities (neural tube defects)

Nonnucleoside: Efavirenz

9

Long-term complications of ART include 1). The statins are used to lower lipids but their metabolism is inhibited by 2). This can increase the blood levels of the statin and increase the risk of 3)

1) hyperlipidemia 2) Protease Inhibitorss 3) rhabdomyolysis

10

used to "boost" the levels of other protease inhibitors when given in combination, thus acting as a pharmacokinetic enhancer rather than an antiretroviral agent

Ritonavir boost

11

nucleoside analog of cytosine

Lamivudine

12

Life cycle of HIV:Reverse transcription HIV is equipped with 1)

1) RNA-dependent DNA polymerase (reverse transcriptase);

13

These drugs do not compete with nucleoside triphosphates nor require phosphorylation to be active

Nonnucleoside: Efavirenz

14

(nucleotide analog of adenosine

Tenofovir

15

All newborns born to HIV-infected mothers should receive 1) for 6 weeks; Infants born to mothers with no antiretroviral therapy should receive 6 weeks of 2) during the first week of life

1) zidovudine 2) zidovudine and three doses of nevirapine (an NNRTI)

16

gp120 and gp41 is made from cleavage of 1); functions of each?

gp160 gp120--> binds to CD4 gp41--> membrane fusion

17

prevent post-translational cleavage of the Gag-Pol polyprotein resulting in the production of immature, noninfectious viral particle

Protease inhibitors: Atazanavir, Darunavir, Ritonavir

18

bind directly to reverse transcriptase resulting in allosteric inhibition of RNA- and DNA-dependent DNA polymerase

Nonnucleoside: Efavirenz

19

integrase strand transfer inhibitor (INSTI)

Integrase inhibitor: raltegravir

20

Life cycle of HIV: Penetration Viral gp120 binding to CD4 is enhanced by further binding to chemokine receptors, 1)

1) CCR5 and CXCR4.

21

Incorporation into the growing viral DNA chain results in premature chain termination due to inhibition of binding with the incoming nucleotide

NRTIs (Emtricitabine, Lamivudine, Tenofovir):

22

Protease Inhibitor therapy in pregnant women a/e

Hyperglycemia Premature birth

23

increases drug exposure, thereby prolonging the drug's half-life and allowing reduction in frequency; in addition, the genetic barrier to resistance is raised

Ritonavir boosting

24

what is protease? cleaves the large precursor 1) into functional proteins which produce a complete virus; Without this step, 2)

1) polypeptide, known as gag-pol, 2) the virion is immature and unable to infect other cells.

25

1) catalyzes the process that results in viral DNA insertion into the host genome. 2) block the enzyme’s activity, preventing viral DNA from integrating with cellular DNA.

1) HIV-1 integrase 2) Integrase strand transfer (InST) inhibitors

26

Prophylaxis of HIV infection: Pre-exposure: oral fixed-dose combination of 1); resistance to 1) if pt infected with HIV so follow-up HIV antibody testing to ensure early diagnosis

1) emtricitabine and tenofovir

27

T/F-->The binding site of NNRTIs is distinct from that of NRTIs

True

28

NRTIs therapy in pregnant women a/e

Mitochondrial dysfunction in uninfected children with perinatal exposure to NRTIs

29

T/F-->there is no cross-resistance between the NRTIs and the NNRTIs

TRUE

30

A/E Peripheral neuropathy, pancreatitis, lipoatrophy, myopathy, anemia, increased transaminases

NRTIs (Emtricitabine, Lamivudine, Tenofovir):

31

fluorinated analog of lamivudine

Emtricitabine

32

HIV treatment during labor: Women who are already in labor and have had no antiretroviral therapy should receive 1) as a continuous infusion to decrease the risk of HIV transmission to the fetus

1) IV zidovudine

33

NRTIs (Emtricitabine, Lamivudine, Tenofovir) are prodrugs which require 1) to be active

1) phosphoylation to the 5'-triphosphate moiety

34

Hepatotoxicity

Penetration blocker: Maraviroc

35

Adverse effects Well-tolerated: diarrhea, nausea, dizziness, and headache

Integrase inhibitor: raltegravir

36

membrane fusion

gp41

37

a/e local injection site reactions with mild or moderate pain, erythema, induration, nodules and cysts

Fusion inhibitor: Enfuvirtide:

38

Life cycle of HIV: Assembly and release a. HIV proteins coalesce under the host cell lipid bilayer b. The nucleocapsid subsequently is formed with 1) and other components packaged inside. c. The virion then 2) d. 3), another enzyme unique to HIV, begins cleaving the large precursor polypeptide, gag-pol, into functional proteins which produce a complete virus. Without this step, the virion is immature and unable to infect other cells

1) viral ssRNA 2) buds through the plasma membrane and maturation begins 3) Protease

39

Drug interactions: Protease inhibitors can inhibit metabolism of drugs as well, in particular, the 1)

1) statins (e.g., atorvastatin, lovastatin, and others).

40

Life cycle of HIV: Integration The dsDNA migrates into the 1) and is integrated into the host chromosome by 2) another enzyme unique to HIV

1) nucleus 2) integrase,

41

Integrase inhibitor: raltegravir resistance

Mutation in integrase

42

Reverse transcription: i. A cDNA is first synthesized using 1) as a template ii. The RNA portion of the cDNA-RNA hybrid is removed by 2) iii. 3) then completes the synthesis of doublestranded DNA

1) viral RNA 2) ribonuclease H (RNase H) 3) Reverse transcriptase

43

Fusion inhibitor: Enfuvirtide resistance

due tospecific mutations in the enfuvirtide-binding domain of gp41

44

Adverse effects i. Cough, pyrexia, upper respiratory tract infection, rash, musculoskeletal symptoms, abdominal pain and postural dizziness

Penetration blocker: Maraviroc

45

T/F--.Most clinicians believe that the benefit of a potent antiretroviral regimen taken during pregnancy greatly outweighs the risk.

True

46

Ketoconazole drug interaction with Maraviroc

Inhibitors of P450 (and P-glycoprotein) (e.g., ketoconazole, macrolide antibiotics) increase the effects of maraviroc; may need to decrease dose

47

Life cycle of HIV: Uncoating After internalization, the viral protein shell surrounding the 1) is uncoated in preparation for replication.

1) nucleic acid (capsid)

48

Life cycle of HIV: Penetration CD4 and coreceptor binding (i.e., binding to CCR5 or CXCR4) promotes membrane fusion which is mediated by 1)

1) gp41

49

Pregnancy HIV treatment: In treatment-naive women, 1) and lamivudine plus either lopinavir/ritonavir or atazanavir/ritonavir

1) zidovudine (an NRTI)

50

NRTIs (Emtricitabine, Lamivudine, Tenofovir): -triphosphate moiety inhibits 1) by competing with endogenous deoxynucleotides for the catalytic site of the enzyme

1) reverse transcriptase

51

Hepatotoxicity (more common in patients who are co-infected with HBV or HCV

Protease inhibitors: Atazanavir, Darunavir, Ritonavir

52

Life cycle of HIV: Penetration The outer glycoprotein, gp160, on the surface of HIV is composed of two subunits 1). The 2) subunit is responsible for CD4 binding

1) gp120 and gp41 2) gp120

53

Life cycle of HIV:Reverse transcription The genetic material of HIV is 1) (5' to 3') 2) The virus must transcribe this RNA into DNA

1) positive-sense 2) single-stranded RNA

54

Adverse effects i. Mitochondrial toxicity due to inhibition of mitochondrial DNA polymerase-γ

NRTIs (Emtricitabine, Lamivudine, Tenofovir):