Flashcards in 11.1 Antiretrovirals Deck (15):
Which drug has an AE of hypersensitivity’ reaction (one or more of rash, GI,
malaise, respiratory distress).
What is the MOA of NNRTI's?
• Highly selective, noncompetitive inhibitors of HIV-1 RT
• Bind at a distinct site away from active site (NNRTI pocket)
• All NNRTI’s bind within the same pocket
• All result in inhibition of RNA- and DNA-dependent
• DO NOT REQUIRE PHOSPHORYLATION BY
• Lack in vitro activity against HIV-2
What are the disadvantages of NNRTI's?
• Cross-resistance with NNRTIs
• Drug Interactions
• High incidence of hypersensitivity reactions (eg, rash)
What are the adverse effects of NNRTI's?
• Skin rash (including Stevens-Johnson syndrome)
• GI intolerance
• All are CYP3A4 substrates and can act as inducers, inhibitors or both of CYPs
Which NNRTI induces CYP3A4?
Which NNRTI is teratogenic?
What is Etravirine metabolized by?
CYP 3A4, 2C9 and 2C19
What are contraindications of Etravirine?
• CYP 3A4 inducer
• CYP 2C9 and 2C19 inhibitor
What are the adverse effects of Etravirine?
• Rash (normally resolves within 1-2 weeks), nausea,
• Transaminase elevations (esp. in patients co-infected
What is the current preferred NNRTI?
What are the most common AE with efavirenz?
• Mostly CNS (50%) (dizziness, headache, vivid dreams,
loss of concentration) – resolve after few weeks.
What are the contraindications of Efavirenz?
• Potent inducer of CYP P450 enzymes.
• Pregnancy (D) (can be used after 1st trimester if
considered best choice)
What is the MOA of Protease Inhibitors?
• Reversible inhibitors of HIV aspartyl protease (enzyme responsible for cleavage of viral polyprotein into RT, protease & integrase)
• Protease inhibition prevents virus maturation & results in production of non-infectious virions
• DO NOT REQUIRE INTRACELLULAR ACTIVATION
• Active against both HIV-1 and HIV-2
What is important to know about the PK of Protease Inhibitors?
• Substrates for CYP 3A4
• Substrates for P-glycoprotein pump