Protease Inhibitors Flashcards
What are the Protease Inhibitors
Ritonavir Atazanavir Indinavir Nelfinavir Fosamprenavir Lopinavir Saquinavir Tirranavir Darunavir
What does HIV aspartyl protease do
Cleaves HIV polyprotein into RT, protease and integrase
Do PIs need intracellular activation
No
What is the problem with the low protease bioavailability
Can be affected by high fat meals
What are Protease inhibitors substrates for
3A4
P-glycprotein
What are the general PI AE
Paresthesia
N/V/D
What are the main PI AE
Lipodystrophy - looks like cushings
Hyperglycemia and Insulin resistance
Crystal induced Nephropathy
Which PI has least AE
Atazanavir
PI interaction with statins
Rabdomyolysis
PI interaction with Midazolam
Excessive sedation
PI interaction with Fentanyl
Resp depression
What drugs are contraindicated with PI
Rifampin
St. John’s Wort
What is the main effect of Ritonavir
Enhancer of other PIs due to 3A4 inhibition
What are the only once-daily preferred PIs
Ritonavir + Atazanavir
What is a preferred PI that can causes insulin resistance
Lopinavir
Which PI can inhibit PPIs
Atazanavir
What are the main Atazanavir AE
Jaundice
Increased PR interval
Which PI cannot be boosted by Ritonavir
Nelfinavir
Indinavir AE
Renal stones/Hematuria
Hyperbilirubinemia
How do you control Nelfinavir diarrhea
Loperamide
Major metabolite has equal anti-viral activity as parent
Nelfinavir
Pro-drug with lots of contraindications
Fosamprenavir
Oral solution contains EtOH
Lopinavir
What should you avoid when on Lopinavir
Disulfiram
Metro
P450 inducers (St. John’s Wort)
High fat meals enhance absorption
Saquinavir
Saquinavir Contraindications
P450 inducers
When is Tipranavir/Darunavir given
Resistant to other PIs
Tipranavir AE
Fatal Hep
Intracranial Hemorrhages
Effect of Tipranavir on P450
Inducer
Inhibitor of 3A4
Darunavir
Darunavir AE
Rash
Can Darunavir be given with food
Yes
