Antiretroviral Drugs- Protease Inhibitors Flashcards
How are gag-pol gene propeptide products processed?
by HIV encoded viral aspartyl protease
PI’s are not indicated for what therapy?
monotherapy- due to resistance
Chronic use of PI’s may be associated with what adverse effects?
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
PI’s are metabolized how?
by CYP3A4
List the 10 PI’s:
1) Amprenavir
2) Atazanavir
3) Fosamprinavir
4) Indinavir
5) Lopinavir + Ritonavir
6) Nelfinavir
7) Saquinavir
8) Ritonavir
9) TIpranavir
10) Darunavir
Amprenavir is what % plasma bound?
> 90%
Amprenavir is metab’d by what?
CYP3A4- caution used in hepatic insufficiency
Amprenavir resistance is due to…
mutations of 150V
Amprenavir AE:
n/v/d, perioral parasthesias, depression and rash
Oral solution of Amprenavir contains what and is CI’d in what population?
propylene glycol and vit. E- so it’s CI’d in children, pregnant women, and in combo with disulfiram or metronidazole
Atazanivir is metabolized by
CYP3A4
Atazanivir’s half life is increased via what drug?
Ritonavir (CYP3A4 inhib) increases t1/2 to 11 hours
Atazanivir may cause…
hyper-bilirubinemia, ECG abnormalities at high doses
Atazanivir does not cause…
fat redistribution or dyslipidemias
Atazanavir inhibits
CYP3A4 and CYP2C9
Fosamprenavir is a prodrug of…
amprenavir, which is hydrolyzed in the intestinal epithelium
Indinavir is increased by co-admin of…
ritonavir (pharmacokinetic enhancer), which inhibits CYP3A4 metabolism
Indinavir must be taken how?
on an empty stomach- 65% oral bio
Indinavir is an inhibitor of what?
CYP3A4
Indinavir resistance is due to mutations at what positions?
46 and 82
Indinavir adverse reations:
hyperbilirubinemia & nephrolithiasis (kidney stones) due to drug crystallization to cause renal failure
Lopinavir/ Ritonavir (kaletra) is used how/ MOA?
Subtherapeutic dose of ritonavir is sufficient to increase t1/2 of lopinavir by inhibiting CYP3A4 metab of lopinavir (pharmacokinetic enhancer)
AE of Lopinavir:
n/v/d, abdominal pain, asthenia (loss of strength)
Nelfinavir (viracept) is metab’d by…elim?
CYP3A4 and undergoes fecal elimn
AE of nelfinavir?
diarrhea and flatulence
Nelfinavir is an inhibitor of what enzyme?
CYP3A4
Saquinavir plasma protein %?
> 98%
Saquinavir is avail in what dosage form?
Hard gel capsule (Invirase)
Soft gel capsule (Fortovase)- better oral avail.
Invirase (Saquinavir) with what drug increases oral bio?
ritonavir (CYP3A4 inhibitor)
How is Saquinavir metab’d?
CYP3A4 and subject to EXTENSIVE FIRST PASS EFFECT
How does ritonavir effect saquinivir?
Ritonavir reduces 1st pass effect of saquinavir- and increases bioavail.
Saquinavir is an inhibitor of
CYP3A4
LFT monitored with Saquinivir when used in combo with
delarvirdine
Saquinavir resistance due to mutation of
G48V
Saquinivir AE:
n/v/abdominal discomfort, dyspepsia, rhinitis
Ritonavir is metab’d by what enzymes?
CYP3A4 and CYP2D6
Ritonavir is a substrate and inhibitor of what?
CYP3A4
Ritonavir is exploited to increase bio of what drugs?
Saquinavir and Lopinavir
Tipranavir must be taken with what drug?
Ritonavir to increase efficacy of poor absorption
Tipranvir is CI’d in:
hepatic insuff and sulfa allergy
