Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) medicines work by blocking a process that the HIV virus needs in order to multiply.

HIV (human immunodeficiency virus) is the virus that causes AIDS. Like other viruses, HIV must use a person's own cells to reproduce. However, HIV is a little different from other viruses because it must first convert its genetic material from RNA to DNA. It is the DNA genes that allow HIV to multiply.

HIV alters its genetic material by using a special protein called the reverse transcriptase enzyme. To create DNA, this enzyme uses several different molecular building-blocks.

A Nucleoside Reverse Transcriptase Inhibitors (NRTIs) medication works by tricking reverse transcriptase into thinking it is one of these molecular building blocks. However, it is just different enough that when used to create DNA, NRTIs actually stop the DNA from being made. Without DNA, HIV cannot multiply.

When HIV infects a CD4 cell in a person's body, it copies its own genetic code into the cell's DNA. In this way, the cell is then "programmed" to create new copies of HIV. HIV's genetic material is in the form of RNA. In order for it to infect CD4 cells, it must first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this process.

NRTIs, sometimes called "nucleoside analogues" or "nukes," contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to convert RNA to DNA. When reverse transcriptase uses these faulty building blocks, the new DNA cannot be built correctly. In turn, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell and prevents the cell from producing new virus.

While nucleotide analogues (Viread is the only nucleotide analogue approved at this time) are technically different than nucleoside analogues, they act very much the same way. In order for nucleoside analogues to work, they must undergo chemical changes (phosphorylation) to become active in the body. Nucleotide analogues bypass this step, given that they are already chemically activated.

SIDE EFFECTS AND MITOCHONDRIAL TOXICITY

In general, most patients tolerate treatment with nucleoside reverse transcriptase inhibitors (NRTIs) well. Common side effects during the first weeks of treatment include fatigue, headache, and gastrointestinal problems, which range from mild abdominal discomfort to nausea, vomiting, and diarrhea.

However, NRTIs are capable of causing a wide variety of long-term side effects, including myelotoxicity (bone marrow suppression), lactic acidosis, polyneuropathy (nerve disorder that affects multiple nerves), and pancreatitis (inflamed pancreas).

Long-term side effects theorized to be related to mitochondrial toxicity were first described in 1999. Mitochondria are tiny organelles inside human cells that generate energy from fuels like glucose. When false nucleosides (NRTIs) enter the body's cells, the mitochondrial DNA may become damaged. Cells that have dysfunctional mitochondria die because they are unable to produce energy.

Fast-replicating cells (like those contained in bone marrow) may also be inhibited by NRTIs leading to blood disorders like anemia and neutropenia. Peripheral neuropathy and pancreatitis are also signs of mitochondrial toxicity.

Different NRTIs affect the mitochondria of different types of cells, which is why the side effects of the drugs are distinct from one another. For instance, stavudine is more toxic than abacavir.

NRTI Drugs List :

Brand Name Generic Name Manufacturer Name

Epivir lamivudine, 3TC GlaxoSmithKline

Retrovir zidovudine, azidothymidine, AZT, ZDV GlaxoSmithKline

Ziagen abacavir sulfate, ABC GlaxoSmithKline

Emtriva emtricitabine, FTC Gilead Sciences

Videx didanosine, dideoxyinosine, ddI Bristol Myers-Squibb

Viread tenofovir disoproxil fumarate, TDF Gilead Sciences

Combivir lamivudine and zidovudine GlaxoSmithKline

Trizivir abacavir, zidovudine, and lamivudine GlaxoSmithKline

Zerit stavudine, d4T Bristol Myers-Squibb

Hivid zalcitabine, ddC Hoffmann-La Roche

Atripla efavirenz, emtricitabine and tenofovir disoproxil fumarate Bristol-Myers Squibb and Gilead Sciences