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HIV Pharm > Sheehy > Flashcards

Sheehy Flashcards

1
Q

What kind of virus is HIV?

A

Retrovirus

SsRNA is reverse transcribed into DNA and inserted into the host cell genome

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2
Q

MOA of Maraviroc

A

Binds specifically and selectively to CCR5 to prevent viral entry into the host cell (entry inhibitor)

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3
Q

AE of Maraviroc

A

Generally well tolerated

Systemic allergic reaction followed by hepatoxicity

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4
Q

MOA of Enfuvirtide

A

Binds to gp41 preventing the conformational and structural changes needed to allow fusion of the viral envelope with the host cell membrane

(Fusion inhibitor)

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5
Q

How must enfuvirtide be administered?

A

SubQ

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6
Q

What drug class is included in treatment for all patients beginning antiretroviral therapy?

A

NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors)

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7
Q

MOA of NRTIs

A

Competitive inhibition of HIV reverse transcriptase

Leads to premature chain termination due to inhibition of binding with the incoming nucleotide

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8
Q

What is the one nucleotide RTI?

A

Tenofovir

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9
Q

What are the 6 nucleoside reverse transcriptase inhibitors?

A

Abacavir, didanosine, lamivudine, emtricatibine, stavudine, zidovudine

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10
Q

What drug is also metabolized by alcohol dehydrogenase?

A

Abacavir

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11
Q

What analog is abacavir

A

Guanosine

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12
Q

AEs of abacavir

A

Skin rash in 50% (do not reintroduce abacavir if hypersensitivity is observed)

Constitutional sx, abdominal, and respiratory (dyspnea, pharyngitis, cough)

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13
Q

What analog is didanosine?

A

Deoxyadenosine

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14
Q

AEs of didanosine

A

Dose dependent pancreatitis

Retinal changes with optic neuritis

Increased risk of lactic acidosis and hepatic steatosis when combine with stavudine

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15
Q

What analog is lamivudine

A

Cytosine

[active against HIV and HBV]

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16
Q

Which two drugs select for the same point mutation in HIV reverse transcriptase?

A

Lamivudine and emtricitabine

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17
Q

What analog is emtricitabine

A

Fluorinated analog of lamivudine (which is a cytosine analog) with a long intracellular half-life allowing for once daily dosing

Also active against HIV and HBV

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18
Q

AEs of emtricitabine

A

Hyperpigmentation of the palms or soles (especially in AA’s)

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19
Q

What analog is stavudine

A

Thymidine

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20
Q

AEs of stavudine

A

Dose dependent peripheral sensory neuropathy

Dyslipidemia (more common with stavudine than other NRTIs)

Increased risk of lactic acidosis and hepatic steatosis when combined with didanosine

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21
Q

What analog is zidovudine

A

Deoxythymidine

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22
Q

AEs of zidovudine

A

Macrocytic anemia, neutropenia, GI intolerance, HA, insomnia

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23
Q

What was the first antiretroviral drug to be approved

A

Zidovudine

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24
Q

What analog is tenofovir

A

Acyclic nucleotide analog of adenosine

Active against both HIV and HBV

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25
Q

What 2 drugs enhance oral absorption of tenofovir

A

Disoproxil and alafenamide

26
Q

AEs of tenofovir

A

Generally well tolerated

Flatulence

27
Q

MOA of NN (non-nucleoside)RTIs

A

Binds directly to HIV reverse transcriptase in site distant from active site

Binding causes conformational change in enzyme and leads to reduced activity

(Noncompetitive inhibitors)

28
Q

Why is monotherapy with NNRTIs not preferred?

A

Resistance can rapidly develop

29
Q

How are NNRTIs metabolized

A

By CYP450, so lots of drug interactions

30
Q

What are the 3 first generation NNRTIs

A

Delavirdine

Efavirenz

Nevirapine

31
Q

What are the 2 second generation NNRTIs

A

Etravirine

Rilpivirine

32
Q

AEs of delaviridine

A

Skin rash

Increased aminotransferase levels

33
Q

How is delavirdine metabolized

A

Extensively by CYP3A & CYP2D6

34
Q

What are the benefits of efavirenz

A

Can be given once daily due to increased half life

Typically given in a combo pill of tenofovir and emtricitabine for a once daily pill

35
Q

What is efavirenz metabolized by

A

CYP3A4 & CYP2B6

36
Q

AEs of efavirenz

A

CNS: dizziness, drowsiness, insomnia, NIGHTMARES, HA

Also skin rash

37
Q

What drug is used to prevent transmission of HIV from mother to child

A

Nevirapine

38
Q

What is nevirapine metabolized by

A

CYP3A

39
Q

AEs of nevirapine

A

Rash which can be dose limiting

Liver toxicity

40
Q

What drug was designed to overcome HIV resistance to first generation NNRTIs

A

Etravirine

41
Q

Etravirine is an inducer and inhibitor of which enzymes

A

Inducer: CYP3A4

Inhibitor: CYP2C9 & CYP2C19

42
Q

AEs of rilpivirine

A

Rash, DEPRESSION, headache, insomnia, increased serum aminotransferases

High doses associated with QT prolongation **

43
Q

MOA of INSTIs

A

Integrase strand transfer inhibitors

Binds HIV integrase and inhibits the strand transfer and prevents ligation of reverse-transcribed HIV DNA into the chromosomes of the host cell

44
Q

What are the most common AEs in INSTIs

A

HA and GI effects

45
Q

What are the 3 INSTIs

A

Dolutegravir

Elvitegravir

Raltegravir

46
Q

What are preferred drug combos for treatment naive patients

A

Tenofovir/emtricitabine/dolutegravir

Abacavir/lamivudine/dolutegravir

47
Q

What is the only available form of elvitegravir

A

A combo pill of elvitegravir, cobicistat, emtricitabine, tenofovir

48
Q

What is the half life for raltegravir

A

9 hours

49
Q

What is the MOA of protease inhibitors

A

Block HIV protease and prevent maturation of the final structural proteins that make up the mature virion core

50
Q

AEs of protease inhibitors

A

GI intolerance

Lipodystrophy (hyperglycemia, hyperlipidemia, lipoatrophy, fat deposition)

Redistribution and accumulation of body fat

51
Q

What are protease inhibitors metabolized by

A

CYP3A4

52
Q

Which drug has the most pronounced inhibitory effect on CYP3A4?

The least?

A

Most: Ritonavir

Least: Saquinavir

53
Q

Which drug inhibits CYP3A4, CYP2C9, UGT1A1?

A

Atazanavir

54
Q

What drug has to be co-administered with ritonavir or cobicistat

A

Darunavir

55
Q

Which drugs can lead to a potential hypersensitivity reaction in someone who has a sulfa allergy?

A

Darunavir, fosamprenavir, tipranavir

56
Q

AEs of indinavir

A

Unconjugated hyperbilirubinemia and nephrolithiasis

57
Q

Which protease inhibitor is a very potent CYP450 inhibitor

A

Ritonavir

58
Q

Which protease inhibitor is indicated in patients resistant to other protease inhibitors

A

Tipranavir

Which is normally combined with ritonavir

59
Q

AEs of tipranavir

A

Abd sx

Urticarial or maculopapular rash

60
Q

What combo of drugs make up a highly active antiretroviral therapy (HAART)

A

2 NRTIS +

1 protease inhibitor OR 1 NNRTI OR 1 INSTI

HIV Pharm (1 decks)

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