Antiretroviral Drugs- Protease Inhibitors

Question 1

How are gag-pol gene propeptide products processed?

Answer 1

by HIV encoded viral aspartyl protease

Question 2

PI’s are not indicated for what therapy?

Answer 2

monotherapy- due to resistance

Question 3

Chronic use of PI’s may be associated with what adverse effects?

Answer 3

Redistribution/ accumulation of body fat resulting in:

1) central obesity
2) dorsocervical fat enlargement (buffalo hump)
3) peripheral and facial wasting
4) breast enlargement
5) cushingold appearance

Question 4

PI’s are metabolized how?

Answer 4

by CYP3A4

Question 5

List the 10 PI’s:

Answer 5

1) Amprenavir
2) Atazanavir
3) Fosamprinavir
4) Indinavir
5) Lopinavir + Ritonavir
6) Nelfinavir
7) Saquinavir
8) Ritonavir
9) TIpranavir
10) Darunavir

Question 6

Amprenavir is what % plasma bound?

Answer 6

> 90%

Question 7

Amprenavir is metab’d by what?

Answer 7

CYP3A4- caution used in hepatic insufficiency

Question 8

Amprenavir resistance is due to…

Answer 8

mutations of 150V

Question 9

Amprenavir AE:

Answer 9

n/v/d, perioral parasthesias, depression and rash

Question 10

Oral solution of Amprenavir contains what and is CI’d in what population?

Answer 10

propylene glycol and vit. E- so it’s CI’d in children, pregnant women, and in combo with disulfiram or metronidazole

Question 11

Atazanivir is metabolized by

Answer 11

CYP3A4

Question 12

Atazanivir’s half life is increased via what drug?

Answer 12

Ritonavir (CYP3A4 inhib) increases t1/2 to 11 hours

Question 13

Atazanivir may cause…

Answer 13

hyper-bilirubinemia, ECG abnormalities at high doses

Question 14

Atazanivir does not cause…

Answer 14

fat redistribution or dyslipidemias

Question 15

Atazanavir inhibits

Answer 15

CYP3A4 and CYP2C9

Question 16

Fosamprenavir is a prodrug of…

Answer 16

amprenavir, which is hydrolyzed in the intestinal epithelium

Question 17

Indinavir is increased by co-admin of…

Answer 17

ritonavir (pharmacokinetic enhancer), which inhibits CYP3A4 metabolism

Question 18

Indinavir must be taken how?

Answer 18

on an empty stomach- 65% oral bio

Question 19

Indinavir is an inhibitor of what?

Answer 19

CYP3A4

Question 20

Indinavir resistance is due to mutations at what positions?

Answer 20

46 and 82

Question 21

Indinavir adverse reations:

Answer 21

hyperbilirubinemia & nephrolithiasis (kidney stones) due to drug crystallization to cause renal failure

Question 22

Lopinavir/ Ritonavir (kaletra) is used how/ MOA?

Answer 22

Subtherapeutic dose of ritonavir is sufficient to increase t1/2 of lopinavir by inhibiting CYP3A4 metab of lopinavir (pharmacokinetic enhancer)

Question 23

AE of Lopinavir:

Answer 23

n/v/d, abdominal pain, asthenia (loss of strength)

Question 24

Nelfinavir (viracept) is metab’d by…elim?

Answer 24

CYP3A4 and undergoes fecal elimn

Question 25

AE of nelfinavir?

Answer 25

diarrhea and flatulence

Question 26

Nelfinavir is an inhibitor of what enzyme?

Answer 26

CYP3A4

Question 27

Saquinavir plasma protein %?

Answer 27

> 98%

Question 28

Saquinavir is avail in what dosage form?

Answer 28

Hard gel capsule (Invirase)

Soft gel capsule (Fortovase)- better oral avail.

Question 29

Invirase (Saquinavir) with what drug increases oral bio?

Answer 29

ritonavir (CYP3A4 inhibitor)

Question 30

How is Saquinavir metab’d?

Answer 30

CYP3A4 and subject to EXTENSIVE FIRST PASS EFFECT

Question 31

How does ritonavir effect saquinivir?

Answer 31

Ritonavir reduces 1st pass effect of saquinavir- and increases bioavail.

Question 32

Saquinavir is an inhibitor of

Answer 32

CYP3A4

Question 33

LFT monitored with Saquinivir when used in combo with

Answer 33

delarvirdine

Question 34

Saquinavir resistance due to mutation of

Answer 34

G48V

Question 35

Saquinivir AE:

Answer 35

n/v/abdominal discomfort, dyspepsia, rhinitis

Question 36

Ritonavir is metab’d by what enzymes?

Answer 36

CYP3A4 and CYP2D6

Question 37

Ritonavir is a substrate and inhibitor of what?

Answer 37

CYP3A4

Question 38

Ritonavir is exploited to increase bio of what drugs?

Answer 38

Saquinavir and Lopinavir

Question 39

Tipranavir must be taken with what drug?

Answer 39

Ritonavir to increase efficacy of poor absorption

Question 40

Tipranvir is CI’d in:

Answer 40

hepatic insuff and sulfa allergy