Nucleoside reverse transcriptase inhibitors (NRTIs)

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Nucleoside reverse transcriptase inhibitors (NRTIs)

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A 32-year-old woman, gravida 1, para 0, at 38-weeks gestation, presents to labor and delivery triage after several hours of contractions. Currently, they are timed about four minutes apart. She does not have fluid leakage, but she noted a small amount of blood on her underwear just before coming into the hospital. The patient was diagnosed with HIV in the first trimester of pregnancy. The patient has been inconsistent with her combination antiretroviral therapy, and her most recent viral load is 15,000 copies/mL. Temperature is 98.9°F (37.1°C), pulse is 98/min, respirations are 16/min, and blood pressure is 132/84 mm Hg. Pelvic examination in triage reveals a cervix that is three centimeters dilated with a small amount of blood near the introitus. The amniotic fluid sac is tense and palpable. Fetal heart rate tracing is a category I. Which of the following is the best next step in managing this patient?  

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Abacavir p. 196, 199

Transcript

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Reverse transcriptase inhibitors are an important part of HAART, or highly active antiretroviral therapy, which is the combination of medications used in the treatment of AIDS.

AIDS is caused by a RNA containing retrovirus called human immunodeficiency virus, or HIV.

The “retro” part of retrovirus isn’t referring to its style, but refers to it needing to use an enzyme called reverse transcriptase to transcribe a piece of “proviral” DNA from its RNA.

As the name suggests, reverse transcriptase inhibitors go and inhibit this enzyme, and prevent HIV replication.

Based on their structure, they can be classified into nucleoside reverse transcriptase inhibitors, or NRTIs; and non-nucleoside reverse transcriptase inhibitors, or NNRTIs.

NRTIs resemble nucleosides, which are tiny molecules which when attached to a phosphate group give rise to nucleotides, which are building blocks of nucleic acids like DNA and RNA.

HIV is a single-stranded, positive-sense, enveloped RNA retrovirus that targets cells in the immune system that have a molecule called CD4 on their membrane.

These include macrophages, dendritic cells, and especially CD4+ T-helper cells.

Normally, the CD4 molecule helps these cells attach to and communicate with other immune cells, which is particularly important when the cells are launching attacks against foreign pathogens.

HIV attaches to the CD4 molecule via a protein called gp120 found on its envelope.

Now, inside its envelope, HIV contains a nucleocapsid which is a capsule containing a single-stranded RNA and some viral enzymes, like reverse transcriptase and integrase.

As HIV bind to the receptors, the viral envelope fuses with the cell membrane of the immune cell, releasing the contents of the nucleocapsid into the helpless host cell’s cytoplasm.

Once it’s inside the CD4+ cell, reverse transcriptase gets to work immediately.

It uses the single stranded viral RNA as a template, and uses the nucleotides present in the cytoplasm of the CD4+ cell to transcribe a complementary double-stranded “proviral” DNA.

Proviral just means that it’s ready to be integrated into the host’s DNA, so it enters the T-helper cell’s nucleus and pops itself into the cell’s DNA, ready to be transcribed into new viruses, pretty sneaky, huh?

Summary

Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of antiviral drugs used to manage HIV infection, which work by inhibiting HIV's reverse transcriptase enzyme. This enzyme prevents the multiplication of the virus and slows down the progression of the disease. Medications in this class include zidovudine, stavudine, lamivudine, didanosine, and tenofovir. Common side effects may include gastrointestinal disturbances like nausea, vomiting, abdominal pain, insomnia, and headache.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "A Review of the Toxicity of HIV Medications" Journal of Medical Toxicology (2013)
  5. "Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus" PLOS ONE (2016)