Anti-HIV: Protease Inhibitors

Question 1

Saquinavir

Answer 1

• mechanism: prevents post-translational cleavage of Gag-Pol polyprotein into functional conformation
• kinetics: oral (enhanced absorption after fatty meal)
• clinical: HIV
• toxicity/interactions: Concurrent use with ritonavir is contraindicated; causes QT and PR interval elongation (associated with arrythmia)
• misc: inhibitor of CYP3A4; many potential drug interactions

Question 2

Ritonavir

Answer 2

• mechanism: prevents post-translational cleavage of Gag-Pol polyprotein into functional conformation
• kinetics: oral (better absorbed with food)
• clinical: HIV
• toxicity/interactions: Concurrent use with saquinavir is contraindicated; causes QT and PR interval elongation (associated with arrythmia)
• misc: potent inhibitor of CYP3A4; results in many potential drug interactions; can be used in combination with other PI drugs to boost their effectiveness

Question 3

Indinavir

Answer 3

• mechanism: prevents post-translational cleavage of Gag-Pol polyprotein into functional conformation
• kinetics: oral (requires acidic environment; best consumed on empty stomach)
• clinical: HIV
• toxicity/interactions: Hyperbilirubinemia and nephrolithiasis due to urinary crystallization of drug
• misc: inhibitor of CYP3A4; many potential drug interactions; concurrent use with ritonavir reduces need for thrice-daily dosing to twice-daily dosing

Question 4

Nelfinavir

Answer 4

• mechanism: prevents post-translational cleavage of Gag-Pol polyprotein into functional conformation
• kinetics: oral (better absorbed with food)
• clinical: HIV
• toxicity/interactions: diarrhea and flatulence
• misc: inhibitor of CYP3A system; many potential drug interactions

Question 5

Amprenavir

Answer 5

• mechanism: prevents post-translational cleavage of Gag-Pol polyprotein into functional conformation
• kinetics: oral (consumed in prodrug form, fosamprenavir, which is readily absorbed with or without food)
• clinical: HIV
• toxicity/interactions: Headache, nausea, diarrhea, perioral paresthesias, depression, and rash (up to 3% experience Stevens-Johnson syndrome)
• misc: inhibitor of CYP3A4; oral solution contains propylene glycol and is contraindicated in young children, pregnant women, patients with renal or hepatic failure; sulfa drug which should not be used in people with sulfa allergies