Nucleoside reverse transcriptase inhibitors

NRTI

Nucleoside reverse transcriptase inhibitors (NRTIs) are analogues of the natural RNA and DNA nucleotides. Zidovudine (AZT) e.g. is a thymidine analogue. This drug is phosphorylated three times, like its natural analogue and together they compete for the reverse transcriptase. The triphosphate drug inhibits the reverse transcriptase. However when transcription still occurs, the triphosphate drug is built in the DNA. The incorporation of nucleoside analogues aborts DNA synthesis and destabilizes the viral double DNA strand. Zidovudine was the first antiretroviral agent. In high doses it can lead to

severe myelotoxicity, but in normal doses it causes only some initial gastrointestinal complaints. Zidovudine is a favourable NRTI because it lacks neurotoxicity and good CNS penetration.

Lamivudine (3TC) is another well-tolerated nucleoside analogue. Its disadvantage is a rapid development of resistance.Lamivudine is also effective against Hepatitis B viruses.

1

Herpes-simplex-virus (HSV) is NOT sensitive to zidovudine (AZT, a reverse transcriptase inhibitor). The reason is that HSV uses its own DNA polymerase for replication.

2

Pregnancy is a contra-indication for the use of zidovudine. 

3

Zidovudine is able to pass the blood-brain-barrier. 

4

Drugs of choice in HIV infections are two NRTIs and a protease inhibitor (triple therapy).