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Zalcitabine

Zalcitabine (2'-3'-dideoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse transcriptase inhibitor (NARTI) sold under the trade name Hivid®. more...

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Zalcitabine is the least potent of all antiretroviral drugs, is inconvenient to take, and has serious side effects. For these reasons it is now rarely used to treat human immunodeficiency virus (HIV).

History

Zalcitabine was developed in the National Cancer Institute (NCI) by Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan at the National Cancer Institute (NCI). Like didanosine, it was then licensed because the NCI may not market drugs. The National Institutes of Health (HIH) thus licensed it to Hoffman LaRoche Co.

Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV infection and AIDS. It was approved on Jun 19, 1992 as a monotherapy and again in 1996 for use in combination with Zidovudine (AZT). Using combinations of NRTIs was in practice prior to the second FDA approval and the triple drug combinations with dual NRTIs and a protease inhibitor (PI) were not far off by this time.

Mechanism of action

Zalcitabine is an analog of pyrimidine. It is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl group in position 3' with a hydrogen.

It is phosphorylated in the T cell and other HIV target cells into its active triphosphate form, ddCTP. This active metabolite works as a substrate for HIV reverse transcriptase, and also by incorporation into the viral DNA, hence terminating the chain elongation due to the missing hydroxyl group. Since zalcitabine is a reverse transcriptase inhibitor it possess activity only against retroviruses. It is used for the treatment of HIV infection only in combination with zidovudine.

Zalcitabine has a very high oral absorption rate, of over 80%. The most common side effect in the beginning of the treatment is nausea and headache. The more serious side effects are peripheral neuropathy, oesophagitis and pancreatitis.

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HIV drugs approved as of August 2003
From AIDS Treatment News, 7/25/03

Here are all the antiretroviral drugs approved in the U.S. at the end of July 2003. We list them by drug class:

* NRTIs (nucleoside reverse transcriptase inhibitor) target reverse transcriptase (an enzyme of HIV), by providing false building blocks that the enzyme puts into new copies of the virus it is building. Occasionally the false building blocks can be incorporated into human DNA, causing toxicity.

* NNRTIs (non-nucleoside reverse transcriptase inhibitor) target the same reverse transcriptase enzyme, but do not provide false building blocks.

* Protease inhibitors target HIV protease, an enzyme necessary for late steps in the formation of new copies of HIV. Some protease inhibitors may inhibit certain human proteases as well, causing toxicity.

* Fusion inhibitors block infection early by preventing HIV from fusing with and entering a human cell. Only one fusion inhibitor has been approved so far, and this particular drug is expensive to manufacture and difficult to use.

None of these drugs can be taken alone to treat an established HIV infection. They must be used in well-designed combination regimens.

NRTIs:

Abacavir (Ziagen)

Didanosine--ddI (Videx)

Emtricitabine--FTC (Emtriva--previous brand name Coviracil)

Lamivudine--3TC (Epivir)

Stavudine--d4T (Zerit)

Tenofovir DF (Viread)

Zalcitabine--ddC (Hivid,)

Zidovudine--AZT (Retrovir)

NNRTIs

Delavirdine (Rescriptor)

Efavirenz (Sustiva, brand name Stocrin in many countries)

Nevirapine (Viramune)

Protease Inhibitors:

Amprenavir (Agenerase)

Atazanavir (Reyataz, formerly named Zrivada)

Indinavir (Crixivan)

Lopinavir+ritonavir (Kaletra)

Nelfinavir (Viracept)

Ritonavir (Norvir)

Saquinavir (Fortovase, earlier formulation Invirase)

Fusion Inhibitors

Enfuvirtide (Fuzeon)

Combination Medications

These brand names are combinations of two or three of the medicines above in one pill. Combinations reduce the number of pills patients must take each day. They can also help meet requirements of health plans that limit the number of "prescriptions" per month regardless of medical need.

Combivir (AZT + 3TC)

Trizivir (abacavir + AZT + 3TC)

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