11.1 Antiretrovirals Flashcards Preview

Pharmacology > 11.1 Antiretrovirals > Flashcards

Flashcards in 11.1 Antiretrovirals Deck (15):
1

Which drug has an AE of hypersensitivity’ reaction (one or more of rash, GI,
malaise, respiratory distress).

Abacavir

2

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
DNA polymerase

• DO NOT REQUIRE PHOSPHORYLATION BY
CELLULAR ENZYMES

• Lack in vitro activity against HIV-2

3

What are the disadvantages of NNRTI's?

• Cross-resistance with NNRTIs

• Drug Interactions

• High incidence of hypersensitivity reactions (eg, rash)

4

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

5

Which NNRTI induces CYP3A4?

Nevirapine

6

Which NNRTI is teratogenic?

Delavirdine

7

What is Etravirine metabolized by?

CYP 3A4, 2C9 and 2C19

8

What are contraindications of Etravirine?

• CYP 3A4 inducer
• CYP 2C9 and 2C19 inhibitor

9

What are the adverse effects of Etravirine?

• Rash (normally resolves within 1-2 weeks), nausea,
diarrhea
• Transaminase elevations (esp. in patients co-infected
with hepatitis)

10

What is the current preferred NNRTI?

Efavirenz

11

What are the most common AE with efavirenz?

• Mostly CNS (50%) (dizziness, headache, vivid dreams,
loss of concentration) – resolve after few weeks.

12

What are the contraindications of Efavirenz?

• Potent inducer of CYP P450 enzymes.
• Pregnancy (D) (can be used after 1st trimester if
considered best choice)

13

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

14

What is important to know about the PK of Protease Inhibitors?

• Substrates for CYP 3A4
• Substrates for P-glycoprotein pump

15

What are the adverse effects of Protease Inhibitors?

• Parathesias, nausea, vomiting, diarrhea

• Disturbances in lipid metabolism (diabetes,
hypertriglyceridemia, hypercholesterolemia)

• Chronic admin -> fat redistribution & accumulation
resulting in central obesity, dorsocervical fat enlargement, peripheral & facial wasting, breast enlargement and a
cushingoid appearance

• Atazanavir has less side effects than other PI’s