Nucleoside reverse transcriptase inhibitors
Ending the viral DNA chain as false nucleotides for reverse transcriptase.
Also called NRTIs.
Class card
- Drugs
- Tenofovir, Lamivudine and Zidovudine
- Used for
- HIV-1 infection, in combination
- Chronic hepatitis B (tenofovir, lamivudine)
- HIV prevention, such as PrEP and in pregnancy
- Known for
- Lactic acidosis with fatty, enlarged liver
- Severe hepatitis B flare when stopped
- Anemia and neutropenia (zidovudine)
- Name stems
- -vir, -fovir, -vudine
4 cards: the class, and each drug in it.
Mechanism of action
How do nucleoside reverse transcriptase inhibitors work?
NRTIs are nucleoside or nucleotide look-alikes. Cell kinases phosphorylate them to their active forms, which compete with natural nucleotides at the active site of HIV reverse transcriptase. Once built into the viral DNA copy they end the chain, so HIV cannot make DNA from its RNA. Some also block the hepatitis B polymerase, and they weakly inhibit human DNA polymerases.
The drugs
Nucleoside reverse transcriptase inhibitors with a card
- TenofovirTenofovir alafenamide (TAF), a newer prodrug, is turned into tenofovir mainly inside cells; in hepatitis B trials it lowered bone density less than tenofovir disoproxil.
- LamivudineHIV becomes resistant through a single reverse transcriptase mutation, M184V or M184I, so it must always be combined with other antiretrovirals.
- ZidovudineIts boxed warnings for marrow toxicity and myopathy set it apart from tenofovir and lamivudine.
Uses
What are nucleoside reverse transcriptase inhibitors used for?
- HIV-1 infection, in combination
- Chronic hepatitis B (tenofovir, lamivudine)
- HIV prevention, such as PrEP and in pregnancy
Side effects
Side effects of nucleoside reverse transcriptase inhibitors
- Lactic acidosis with fatty, enlarged liverKnown forSerious
- Severe hepatitis B flare when stoppedKnown forSerious
- Anemia and neutropenia (zidovudine)Known forSerious
- Kidney injury and Fanconi syndrome (tenofovir)Serious
- Loss of bone density (tenofovir)
- Myopathy (zidovudine)Serious
- Body fat loss or redistribution
- PancreatitisSerious
- Headache, nausea and tiredness
- Immune reconstitution syndromeSerious
What the class has in common. Each drug's card has its own, and Known for marks what an exam expects you to know.
Watch for
Cautions
- Test for hepatitis B first: stopping tenofovir or lamivudine in hepatitis B can cause a severe flare, so liver tests continue for months.
- Tenofovir: check kidney function before and during treatment, and avoid other nephrotoxic drugs such as high-dose NSAIDs.
- Zidovudine: check blood counts, and avoid other marrow-suppressing drugs such as ganciclovir.
- Never used alone for HIV: resistance develops, so they are combined with other antiretrovirals.
Remember them
A way to remember them
NRTIs are fake bricks: the wall of viral DNA stops where they are laid.
Reverse transcriptase picks up the false nucleotide and builds it into the DNA copy of HIV's RNA, and no further bricks can be added: chain termination.
Written for biofideX
Name stems
-vir means antiviral
Sub-stems name the target: -ciclovir, -amivir, -fovir, -tegravir, -navir, -buvir, -virine (NNRTIs). Lamivudine and zidovudine are antivirals without it.
-fovir means phosphonate nucleotide antiviral
Tenofovir and adefovir are phosphonate nucleotide analogues. Tenofovir blocks the reverse transcriptase of both HIV-1 and hepatitis B virus.
-vudine means nucleoside antiviral (zidovudine type)
Zidovudine and lamivudine block HIV reverse transcriptase, and lamivudine also treats hepatitis B. WHO files -vudine under -uridine.
- Every drug name stem
Don't mix them up
Classes easily confused with these
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- Nucleoside Reverse Transcriptase Inhibitor (NCI Thesaurus)
- Tenofovir disoproxil fumarate tablets: label (DailyMed)
- Lamivudine tablets: label (DailyMed)
- Zidovudine tablets: label (DailyMed)
- HIV and AIDS: fact sheet (WHO)
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Antivirals
Practice nucleoside reverse transcriptase inhibitors with the other classes in this group: what each drug is, how it works, what it treats and what it's known for.
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