chemistry

Zalcitabine

Zalcitabine is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Zalcitabine rather than just read about it. In short: Zalcitabine (2′-3′-dideoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV/AIDS.

Key takeaways

Zalcitabine belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Zalcitabine to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Zalcitabine from memory before moving on to harder problems.

Reference excerpt

Zalcitabine (2′-3′-dideoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV/AIDS. It is used as part of a combination regimen. Zalcitabine appears less potent than some other nucleoside RTIs, has an inconvenient three-times daily frequency and is associated with serious adverse events. For these reasons it is now rarely used to treat human immunodeficiency virus (HIV), and it has even been removed from pharmacies entirely in some countries.

Medical uses Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV/AIDS. It was approved on June 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. In 1992 dideoxycytidine was listed as a specialty drug. The sale and distribution of zalcitabine has been discontinued since December 31, 2006.

Drug interactions Lamivudine (3TC) significantly inhibits the intracellular phosphorylation of zalcitabine to the active form, and accordingly the drugs should not be administered together. Additionally, zalcitabine should not be used with other drugs that can cause peripheral neuropathy, such as didanosine and stavudine.

Adverse events The most common adverse events at the beginning of treatment are nausea and headache. More serious adverse events are peripheral neuropathy, which can occur in up to 33% of patients with advanced disease, oral ulcers, oesophageal ulcers and, rarely, pancreatitis.

Resistance Resistance to zalcitabine develops infrequently compared with other nRTIs, and generally only occurs at a low level. The most common mutation observed in vivo is T69D, which does not appear to give rise to cross-resistance to other nRTIs; mutations at positions 65, 74, 75, 184 and 215 in the pol gene are observed more rarely.

Pharmacology

Pharmacokinetics Zalcitabine has a very high oral absorption rate of over 80%. It is predominantly eliminated by the renal route, with a half-life of 2 hours.

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 T cells 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. Apart from inhibiting retroviral reverse transcriptase, ddC inhibits mitochondrial DNA polymerase gamma, resulting in a dose-limiting toxicity.

History Zalcitabine was first synthesized in the 1960s by Jerome Horwitz and subsequently developed as an anti-HIV agent 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 or sell drugs. The National Institutes of Health (NIH) thus licensed it to Hoffmann-La Roche.

References

Illustrations

Worked examples

Example 1 — a first encounter with Zalcitabine

Start with the simplest possible case. Write down what Zalcitabine claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Zalcitabine before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Zalcitabine ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Zalcitabine

In research: Zalcitabine appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Zalcitabine in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Zalcitabine is common in secondary-school and first-year university syllabi. It links to neighbouring topics Drugs developed by Hoffmann-La Roche, Hydroxymethyl compounds, IARC Group 2B carcinogens, so understanding it makes those chapters shorter.
In everyday life: Look for Zalcitabine outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Zalcitabine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Zalcitabine means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Zalcitabine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Zalcitabine in simple terms?

Why does Zalcitabine matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Zalcitabine?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Zalcitabine.