Anti-HIV: NRTI

Question 1

Retrovir

Answer 1

• mechanism: early termination of DNA elongation (pyrmidine analog)
• kinetics: oral
• clinical: HIV
• toxicity/interactions: bone marrow toxicity => leukopenia and anemia
• misc: well tolerated in pregnancy; prophylaxis for all ages

Question 2

Didanosine

Answer 2

• mechanism: early termination of DNA elongation (missing 2’ and 3’ OH groups; ddI => ddATP in host cell)
• kinetics: oral - fasting (because of acid lability), penetrates CSF
• clinical: HIV
• toxicity/interactions: pancreatitis (can be fata), and dose-limiting peripheral neuropathy

Question 3

Zalcitabine

Answer 3

• mechanism: early termination of DNA elongation (cytosine analog )
• clinical: HIV
• toxicity/interactions: HIGH TOXCITY - HAS BEEN REMOVED FROM MARKET

Question 4

Stavudine

Answer 4

• mechanism: early termination of DNA elongation (thymidine analog (double bond for 2’ and 3’ carbons) and strong inhibitor of beta and gamma DNA polymerases)
• kinetics: oral, penetrates BBB
• clinical: HIV
• toxicity/interactions: peripheral neuropathy, lipoatrophy, and hyperlipidemia

Question 5

Lamivudine

Answer 5

• mechanism: early termination of DNA elongation (cytosine analog)
• kinetics: oral (good bioavailability), depends on kidney for excretion
• clinical: HIV and HBV
• toxicity/interactions: well tolerated

Question 6

Abacavir

Answer 6

• mechanism: early termination of DNA elongation (guanosine analog)
• kinetics: oral (well absorbed); metabolized by cytochrome P450
• clinical: HIV
• toxicity/interactions: oral (well absorbed); metabolized by cytochrome P450

Question 7

Tenofovir

Answer 7

• mechanism: early termination of DNA elongation (adenosine analog 5’ monophosphate)
• kinetics: oral (with meal); long half life (one daily dosing); unchanged in urine
• clinical: HIV
• toxicity/interactions: nausea, vomiting, diarrhea, asthenia; less commonly hepatotoxicity, abdominal pain, and flatulance; renal toxicity at higher concentration
• misc: lots of other drug interactions (avoid AZT and tenofovir)

Question 8

Emtricitabine

Answer 8

• mechanism: early termination of DNA elongation (fluro-derivative of Lamivudine)
• kinetics: oral
• clinical: HIV and HBV
• toxicity/interactions: hyperpigmentation of soles and palms, associated with lactic acidosis, fatty liver, and hepatomegaly